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Welcome to the Uterine
and
Cervical Cancer File
Patients all over the world
have used the information in The Uterine and Cervical Cancer
File since 1992, when the Center for Current Researchone
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highly trained researchers (all of whom hold Ph.D.s) have searched
the advanced medical database at the National Library of Medicine
and compiled a comprehensive collection of research descriptions
on Uterine and Cervical Cancer and its care.
As you will see, the following research descriptions detail the
findings published in the most respected journals in the field.
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Previous Uterine Cancer
Research: 2002-2006
The
Uterine and Cervical Cancer File also contains summaries of past
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Latest Research on
Uterine and Cervical Cancer
Gynecol Oncol. 2008 Sep;110(3):293-8. Epub 2008 Jul 21.
Utility of pre-operative serum CA-125 in the management of
uterine papillary serous carcinoma.
Olawaiye AB, Rauh-Hain JA, Withiam-Leitch M, Rueda B, Goodman A, del Carmen MG.
Department of Obstetrics, Division of Gynecologic Oncology, Harvard Medical
School, Vincent Obstetrics and Gynecology Service, Massachusetts General
Hospital, 55 Fruit Street, Boston, MA 02114, USA.
OBJECTIVE: To evaluate the usefulness of pre-operative serum CA-125 in the
management of women diagnosed with uterine papillary serous carcinoma (UPSC). We
hypothesized that elevated pre-operative levels of serum CA-125 correlate with
higher disease stage and poorer prognosis. METHODS: Patients diagnosed with UPSC
and managed in our institution were identified over a period of 10 years, 1995
to 2005. All required information were extracted from their records. The
nonparametric test applied for comparison of data included Kruskal Wallis H-test
and Man-Whitney U-test. The chi(2) test and Spearman correlation test were used
to examine the association of serum CA-125 with different parameters. Receiver
operator characteristic curves (ROC) were used to quantify marker performance.
Recurrence and survival were analyzed using Kaplan-Meier method. Multivariate
analyses were performed with a Cox proportional regression method. RESULTS: A
total of 41 patients met the study criteria. Mean pre-operative serum CA-125
levels were significantly higher in patients with stage IV (1150+/-1297 U/mL),
compared with stage III (181+/-232 U/mL; P<0.001), stage II (22+/-9; P<0.001),
and stage I (14+/-1; P<0.001). CA-125 correlated strongly with stage (r=0.68,
P<0.001). On the ROC, a cut-off of 35 IU/mL provided the best sensitivity and
specificity (78% vs. 100% respectively) for extra-uterine disease. Disease free
survival (DFS) and overall survival (OS) were longer in patients with CA-125<35
U/mL compared with CA-125>or=35 U/mL [median DFS not reached during study vs.
21.2 months (P=0.009), and median OS not reached during study vs. 25 months,
(P=0.0001) respectively]. Multivariate regression model showed CA-125 as the
only variable associated with survival (P=0.05). CONCLUSION: Pre-operative serum
CA-125 levels correlate with stage of disease in patients with UPSC. This may be
important for management planning, prognostication and counseling in these
women.
------
Gynecol Oncol. 2008 Sep;110(3):308-15. Epub 2008 Jul 7.
Clinical efficacy of modified preoperative neoadjuvant
chemotherapy in the treatment of locally advanced (stage IB2 to IIB) cervical
cancer: randomized study.
Chen H, Liang C, Zhang L, Huang S, Wu X.
Department of Gynecologic Oncology, Zhongnan Hospital of Wuhan University, Wuhan,
Hubei Province, China. huijunchen1981@sina.com
OBJECTIVES: The use of preoperative neoadjuvant chemotherapy (NAC) in locally
advanced cervical cancer (LACC) was hindered by the disadvantages of a delay of
curative treatment for nonresponders and the development of radioresistant
cells. However, these disadvantages may be overcome by a 'quick' high-dose
scheme administered in a short period before surgery. Our purpose is to assess
the efficacy of NAC with short cycle-length, high-dose agents for LACC. METHOD:
From 1999 to 2004, 142 of patients with LACC (stage IB2IIB, tumor diameter >or=4
cm) were assigned to randomly receive either NAC followed by surgery or primary
surgery directly. A modified NAC scheme with short cycle-length, high-dose
agents was used. RESULTS: The overall clinical response rate was 69.4%. The
chemotherapeutic response was more favorable in the squamous carcinoma and the
tumors smaller than 8 cmP=0.005, P=0.029). Pathologic findings showed that the
pelvic metastasis and parametrial infiltration rates were significantly lower in
NAC group than in the primary surgery group (P=0.025; P=0.038). Among patients
who received NAC, the lymph node metastasis rate was still as high as 45.5% in
non-NAC responders, and it decreased to 16.0% in NAC responders (P=0.008). The
same thing also occurred with parametrial infiltration: 45.5% in non-NAC
responders compared with 16.0% in NAC responders (P=0.008). Survival analysis
revealed that although test showed a longer survival in NAC group than in the
primary surgery group (P=0.041), Cox hazard analysis did not indicate the
therapy modality as a prognostic predictor (P=0.074). However, after further
subdivision, we found that NAC responders had longer survival and lower
recurrence rate than non-NAC responders (P=0.000; P=0.013). NAC response was
also an independent prognostic predictor (P=0.005). CONCLUSION: The modified
preoperative NAC is well tolerated and beneficial in reducing tumor size,
eliminating pathological risk factors, and improving prognosis for responders.
It also avoids the delay of effective treatment for non-NAC responders.
------
Gynecol Oncol. 2008 Sep;110(3):304-7. Epub 2008 Jul 2.
MVP expression is related to IGF1-R in cervical carcinoma
patients treated by radiochemotherapy.
Lloret M, Lara PC, Bordón E, Rey A, Falcón O, Apolinario RM, Clavo B, Ruiz A.
Radiation Oncology, Dr Negrin University Hospital, Las Palmas de Gran Canaria,
Spain. mllosae@hotmail.com
OBJECTIVE: To assess the expression of MVP in cervix carcinoma patients treated
by radiochemotherapy, its relation to clinical and pathologic prognostic factors
and its role in predicting clinical outcome. In addition the relation to IGF-1R
expression in this cohort of patients will be explored. MATERIALS AND METHODS:
Sixty consecutive patients suffering from localized cervix carcinoma were
prospectively included in this study from July 1999 to December 2003. Follow-up
was closed in November 2007. Patients were staged following the TNM
classification. All patients received pelvic radiation (45-64.80 Gy in 1.8-2 Gy
fractions) followed brachytherapy and concomitant cisplatin at 40 mg/m(2)/week
doses. MVP expression was studied by immunohistochemistry in paraffin-embedded
tumour tissue. RESULTS: MVP was expressed in 58 patients (96.7%) and no relation
was found with clinicopathological variables. High MVP expression was related to
high IGF1-R expression (p=0.023). Complete response after treatment was observed
in 50 patients (83.3%). Clinical stage of the disease and clinical response to
radiochemotherapy were the most important prognostic factors related to
survival. High MVP and IGF-1R tumour expression was strongly related to poor
local and regional disease-free survival (p=0.006), distant disease-free
survival (p=0.050), disease-free survival (p=0.006), and cause-specific survival
(p=0.007) in patients achieving a complete response. CONCLUSION: MVP and IGF-1R
expression were related in clinical cervical tumours and confer reduced
long-term local control in patients who achieved clinical complete response to
radiochemotherapy.
------
Cancer. 2008 Aug 15;113(4):743-9.
Patterns of care for women with cervical cancer in the United
States.
Trimble EL, Harlan LC, Gius D, Stevens J, Schwartz SM.
National Cancer Institute, Surgery Section, Bethesda, Maryland 20892-7436, USA.
tt6m@nih.gov
BACKGROUND: Recommendations for pretreatment evaluation and treatment of
cervical cancer have significantly evolved over the last decade because of the
results of multiple randomized studies comparing the addition of platin-based
chemoradiation as well as the widespread dissemination and use of imaging
modalities. This analysis was initiated to determine any systemic changes in
management of cervical cancers. METHODS: Surveillance, Epidemiology, and End
Results program data were used to sample newly diagnosed women in 1997, 2000,
and 2001 with cancer of the cervix. A total of 3116 women with no previous
diagnosis of cancer were selected. Data were reabstracted, additional
information not routinely collected was obtained, therapy was verified with the
treating physician, and multiple endpoints were analyzed. RESULTS: A marked rise
was observed in the percentage receiving chemotherapy (34% to 85%) as well as
concurrent chemoradiation (20% to 72%) from 1997 to 2001. CONCLUSIONS: The
significant change in the management and treatment of cervical cancer appears to
correspond temporally with the publication of 5 clinical trials, all of which
showed a significant improvement in overall survival associated with
chemoradiation. This change also corresponded with the NCI Clinical Announcement
that was disseminated in 1999 to those oncologists most likely to treat women
with cervical cancer. 2008 American Cancer Society
------
Am J Obstet Gynecol. 2008 Aug;199(2):191.e1-7; discussion 191.e7. Epub 2008 Jun
13.
The vascular portion of the cardinal ligament: surgical
significance during radical hysterectomy for cervical cancer.
Hoffman MS, Williams V, Salihu HM, Gunasekaran S, Sayer RA, Hakam A, Roberts WS.
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology,
University of South Florida College of Medicine, Tampa, FL, USA. mhoffma1@health.usf.edu
OBJECTIVE: The objective of the study was to analyze the histopathologic content
of the vascular portion of the cardinal ligament in patients undergoing radical
hysterectomy for cervical cancer. STUDY DESIGN: The vascular portion of the
cardinal ligament was completely removed during radical hysterectomy. The
maximum cervical diameter and length of the vascular ligament were measured on
the fresh specimen. After inking, the pathologist separated and embedded the
entire vascular segment from each side. Microscopic examination followed.
RESULTS: Eighty-four patients were available for analysis. The mean cervical
diameter was 3.9 cm (2-8), whereas the mean vascular segment length on the right
and left sides were 4 cm (1-10) and 3.8 cm (1-7), respectively. Mean number of
vascular segment lymph nodes were as follows: medial right = 0.7 (0-4), medial
left = 0.6 (0-5), lateral right = 0.4 (0-3), and lateral left = 0.6 (0-6). Mean
diameter of medial and lateral lymph nodes were 2 mm (0.25-8) and 3.3 mm
(0.25-16), respectively. The length of the vascular segment correlated inversely
with maximum cervical diameter. Thirty-one percent (26 of 84) had positive
pelvic side wall lymph nodes. Fourteen patients had positive vascular segment
lymph nodes (1 positive = 7, more than 1 positive = 7). Three of 7 patients had
bilateral positive vascular segment lymph nodes; all 7 had microscopic disease
in the paravaginal soft tissue, and all 7 had positive pelvic side wall lymph
nodes (6 of 7 bilateral). Including the 14 patients, a total of 19 had nodal or
nonnodal microscopic disease in the vascular segment. Of these, 7 had disease in
the lateral half of the vascular ligament. Histologic sectioning revealed nerve
twigs and/or scattered ganglia in the vascular segment but no large nerve
trunks. CONCLUSION: Among a population of women with high-risk, early-stage
cervical cancer, the lateral vascular segment of the cardinal ligament contained
metastatic disease in a substantial number of patients. This segment contains no
major nerve trunks. When radical hysterectomy is chosen as primary treatment for
such patients, the vascular segment of the cardinal ligament should be
completely excised.
------
Br J Radiol. 2008 Aug;81(968):659-65.
Factors predicting tumour regression in locally advanced cervical
adenocarcinoma treated with balloon-occluded intra-arterial chemotherapy.
Niwa T, Yoshida T, Doiuchi T, Ito K, Nakayama H, Odagiri K, Inoue T.
Department of Radiology, Kanagawa Cancer Centre, 1-1-2 Nakao, Asahi-ku,
Yokohama, Japan. tniwa@kcmc.jp
We retrospectively assessed the factors that may impede tumour reduction of
locally advanced cervical adenocarcinoma treated with balloon-occluded arterial
infusion chemotherapy (BOAI) as initial therapy. We reviewed the medical records
and MRI scans of 31 patients (mean age, 54.7 years; age range, 33-78 years).
BOAI was performed via uterine arteries in 21 patients, and via the anterior
division or main trunk of the internal iliac artery (when the uterine arteries
were obscured) in 10 patients. Tumour reduction rate was calculated from the
tumour size on MRI before and after BOAI, and patients given chemotherapy were
classified as "non-responders" or "responders". Factors including the patient's
age, tumour stage (using the International Federation of Gynecology and
Obstetrics classification), the artery used for infusion, infused drug, presence
of intravenous systemic chemotherapy, initial tumour size, tumour volume and
presence of lymph node metastases were assessed for their ability to predict
tumour response to BOAI using univariate and multivariate analyses. Patients who
underwent chemotherapy included 10 non-responders and 21 responders. The age of
non-responders was significantly higher than that of responders (66 years vs 49
years, p<0.001). Internal iliac arterial infusion significantly correlated with
"no response" compared with uterine arterial infusion (p<0.001). In multivariate
analyses, internal iliac arterial infusion was an independent predictor for BOAI
non-responders (odds ratio, 19.6; 95% confidence interval, 1.4-280.6; p = 0.02).
These data suggest that uterine arteries being obscured to arterial infusion may
be associated with a poor response to BOAI for cervical adenocarcinoma.
------
Int J Radiat Oncol Biol Phys. 2008 Aug 1;71(5):1504-10.
Dosimetric comparison of bone marrow-sparing intensity-modulated
radiotherapy versus conventional techniques for treatment of cervical cancer.
Mell LK, Tiryaki H, Ahn KH, Mundt AJ, Roeske JC, Aydogan B.
Department of Radiation Oncology, School of Medicine, University of
California-San Diego, La Jolla, CA, USA.
PURPOSE: To compare bone marrow-sparing intensity-modulated pelvic radiotherapy
(BMS-IMRT) with conventional (four-field box and anteroposterior-posteroanterior
[AP-PA]) techniques in the treatment of cervical cancer. METHODS AND MATERIALS:
The data from 7 cervical cancer patients treated with concurrent chemotherapy
and IMRT without BMS were analyzed and compared with data using four-field box
and AP-PA techniques. All plans were normalized to cover the planning target
volume with the 99% isodose line. The clinical target volume consisted of the
pelvic and presacral lymph nodes, uterus and cervix, upper vagina, and
parametrial tissue. Normal tissues included bowel, bladder, and pelvic bone
marrow (PBM), which comprised the lumbosacral spine and ilium and the ischium,
pubis, and proximal femora (lower pelvis bone marrow). Dose-volume histograms
for the planning target volume and normal tissues were compared for BMS-IMRT vs.
four-field box and AP-PA plans. RESULTS: BMS-IMRT was superior to the four-field
box technique in reducing the dose to the PBM, small bowel, rectum, and bladder.
Compared with AP-PA plans, BMS-IMRT reduced the PBM volume receiving a dose
>16.4 Gy. BMS-IMRT reduced the volume of ilium, lower pelvis bone marrow, and
bowel receiving a dose >27.7, >18.7, and >21.1 Gy, respectively, but increased
dose below these thresholds compared with the AP-PA plans. BMS-IMRT reduced the
volume of lumbosacral spine bone marrow, rectum, small bowel, and bladder at all
dose levels in all 7 patients. CONCLUSION: BMS-IMRT reduced irradiation of PBM
compared with the four-field box technique. Compared with the AP-PA technique,
BMS-IMRT reduced lumbosacral spine bone marrow irradiation and reduced the
volume of PBM irradiated to high doses. Therefore BMS-IMRT might reduce acute
hematologic toxicity compared with conventional techniques.
------
Cancer Res. 2008 Jul 15;68(14):5699-705.
An in vitro multistep carcinogenesis model for human cervical
cancer.
Narisawa-Saito M, Yoshimatsu Y, Ohno S, Yugawa T, Egawa N, Fujita M, Hirohashi
S, Kiyono T.
Virology Division, National Cancer Center Research Institute, Chuo-ku, Tokyo,
Japan.
Human papillomaviruses (HPV) are believed to be the primary causal agents for
development of cervical cancer, and deregulated expression of two viral
oncogenes E6 and E7 in basal cells, mostly by integration, is considered to be a
critical event for disease progression. However, lines of evidence suggest that,
besides expression of E6 and E7 genes, additional host genetic alterations are
required for cancer development. To directly test this hypothesis, we first
transduced HPV16 E6 and E7 with or without hTERT into several lines of normal
human cervical keratinocytes (HCK) from independent donors and then searched for
additional alterations required for carcinogenesis. Oncogenic Hras(G12V) (Hras)
provided marked tumor forming ability in nude mice and ErbB2 or c-Myc (Myc)
endowed weaker but significant tumor forming ability. Combined transduction of
Myc and Hras to HCKs expressing E6 and E7 resulted in the creation of highly
potent tumor-initiating cells. These results show that only one or two genetic
changes occurring after deregulated expression of high-risk HPV oncogenes might
be sufficient for development of cervical cancer.
------
Anticancer Res. 2008 Jul-Aug;28(4C):2385-8.
Feasibility study of docetaxel and nedaplatin for recurrent
squamous cell carcinoma of the uterine cervix.
Watanabe Y, Nakai H, Etoh T, Kanemura K, Tsuji I, Ishizu A, Hoshiai H.
Department of Obstetrics and Gynecology, Kinki University School of Medicine,
377-2 Ohno-Higashi Osakasayama Osaka 589-8511, Japan. watanabe@med.kindai.ac.jp
BACKGROUND: To determine a new taxane plus platinum treatment regimen for
squamous cell carcinoma of the uterine cervix (CSCC), a phase I feasibility
study of docetaxel (DTX) plus nedaplatin (CDGP) combination therapy was
conducted. PATIENTS AND METHODS: Twenty consecutive patients were enrolled into
the study. The starting dose of DTX/CDGP was 60 mg/m2 / 80 mg/m2, every 4 weeks
for at least three courses and the dose was escalated to 70 mg/m2 / 100 mg/m2.
DTX 60 mg/m2 / CDGP 100 mg/m2 was also evaluated as an extra dose level.
RESULTS: Dose-limiting toxicity was granulocytopenia and the maximum tolerated
dose was determined as 70 mg/m2 / 100 mg/m2. All 20 patients had measurable
disease and a partial response was achieved in 8 (40.0%) patients. CONCLUSION:
DTX/CDGP therapy appears to be a tolerable regimen for cervical squamous cell
carcinoma, even in patients previously treated by cisplatin concurrent
chemoradiotherapy. The recommended doses of DTX and CDGP were determined to be
60 mg/m2 and 100 mg/m2, respectively.
------
J Low Genit Tract Dis. 2008 Jul;12(3):181-4.
Human papillomavirus vaccination: the policy debate over the
prevention of cervical cancer—a commentary.
Hoops KE, Twiggs LB.
Department of Obstetrics and Gynecology, University of Miami Miller School of
Medicine, Miami, FL 33101, USA.
The human papillomavirus (HPV) family causes a variety of benign, premalignant,
and malignant lesions in men and women. HPV types 16 and 18 are responsible for
causing 70% of all cases of cervical cancer each year. Recently, a vaccine that
can prevent cervical cancer by protecting women from infection with the most
common types of HPV has been made available. Following Food and Drug
Administration approval and endorsement by the Centers for Disease Control and
Prevention, it is the right and the duty of the state legislatures to implement
vaccination programs. This vaccine, a vaccine for a sexually transmitted
disease, has stirred a fierce debate. Religion and sexuality have dominated the
discussion, and political calculations are inherent to the process; nonetheless,
epidemiological analyses are also essential to the decision to mandate the HPV
vaccine. HPV vaccine program implementation processes are at many stages in many
states, and programs vary widely. Some provide information to families, whereas
others allot a range of funding for voluntary vaccination. Virginia is, thus
far, the only state to have enacted a mandate. This article discusses the
various programs in place, the proposed legislation, and the debate surrounding
the political process.
------
Mol Cancer Ther. 2008 Jul;7(7):2090-5.
Cyclooxygenase inhibitors block uterine tumorigenesis in HMGA1a
transgenic mice and human xenografts.
Di Cello F, Hillion J, Kowalski J, Ronnett BM, Aderinto A, Huso DL, Resar LM.
Hematology Division, The Johns Hopkins University School of Medicine, Baltimore,
MD 21205, USA.
Uterine cancer is a common cause for cancer death in women and there is no
effective therapy for metastatic disease. Thus, research is urgently needed to
identify new therapeutic agents. We showed previously that all female HMGA1a
transgenic mice develop malignant uterine tumors, indicating that HMGA1a causes
uterine cancer in vivo. We also demonstrated that HMGA1a up-regulates
cyclooxygenase-2 (COX-2) during tumorigenesis in this model. Similarly, we found
that HMGA1a and COX-2 are overexpressed in human leiomyosarcomas, a highly
malignant uterine cancer. Although epidemiologic studies indicate that
individuals who take COX inhibitors have a lower incidence of some tumors, these
inhibitors have not been evaluated in uterine cancer. Here, we show that HMGA1a
mice on sulindac (a COX-1/COX-2 inhibitor) have significantly smaller uterine
tumors than controls. To determine if COX inhibitors are active in human uterine
cancers that overexpress HMGA1a, we treated cultured cells with sulindac sulfide
or celecoxib (a specific COX-2 inhibitor). Both drugs block
anchorage-independent growth in high-grade human uterine cancer cells that
overexpress HMGA1a (MES-SA cells). In contrast, neither inhibitor blocked
transformation in cells that do not overexpress HMGA1a. Moreover, xenograft
tumors from MES-SA cells were significantly inhibited in mice on sulindac. More
strikingly, no tumors formed in mice on celecoxib. These preclinical studies
suggest that COX inhibitors could play a role in preventing tumor onset or
progression in uterine cancers with dysregulation of the HMGA1a-COX-2 pathway.
Importantly, these drugs have lower toxicity than chemotherapeutic agents used
to treat advanced-stage uterine cancers.
------
Ther Umsch. 2008 Jun;65(6):341-6.
[Follow-up after malignant tumours of the uterus (cancer of the
uterine corpus / cervical cancer)]
[Article in German]
Johann S, Mueller MD.
Klinik und Polikliniken für Frauenheilkunde, Inselspital, Universitätskliniken
Bern und Universität Bern.
Malignant uterine tumours can affect the corpus or the cervix. The endometrial
carcinoma with its different histological subtypes counts for most of the
malignomas of the uterine body. But the rare category of uterine sarcomas (carcinosarcomas,
leiomyosarcomas as well as endometrial stromal sarcomas) also belongs to this
group. Cervical cancer presents an own entitity, regarding both histology and
therapeutic options. Endometrial cancer is the most common genital malignoma in
Northern Europe and North America. Histologically, the endometrial cancer can be
subdivided in two groups: type I is hormonal sensitive and well differentiated,
type II represents an undifferenciated aggressive tumour with poor prognosis. In
general, the patient is elderly. Due to the main symptom - abnormal vaginal
bleeding - endometrial cancer is detected in an early stage in about 75% of all
patients. First choice in therapy is stage related surgery. Follow-up schemes
have not proved yet to improve survival, therefore clear guidelines are missing.
National and international groups recommend regular follow-up visits to detect
the early vaginal vault relapse which is curable. Cervical cancer is mainly a
squamous cell carcinoma and oncogenic Human Papilloma Virus (HPV) associated.
Surgery is only indicated up to stage IIA, advanced stages should be treated by
radio-chemotherapy. Several studies have shown that follow-up visits can improve
survival rates. Intention is the detection of the curable local relapse.
------
Anal Quant Cytol Histol. 2008 Apr;30(2):63-70.
Expression of p53, bcl-2 and Ki-67 in cervical intraepithelial
neoplasia and invasive squamous cell carcinoma of the uterine cervix.
Looi ML, Dali AZ, Ali SA, Ngah WZ, Yusof YA.
Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia,
Kuala Lumpur, Malaysia.
OBJECTIVE: To assess the expression of p53, bcl-2 and Ki-67 in the progression
of cervical neoplasia. STUDY DESIGN: A total of 131 cervical specimens,
consisting of normal cervical epithelium (n = 43), cervical intraepithelial
neoplasia (CIN) lesions (n =40) and cervical squamous cell carcinomas (SCCs) (n
= 48) were examined immunohistochemically in paraffin sections for expression of
p53, bcl-2 and Ki-67. RESULTS: Immunoreactivity of p53 was found in 27% of SCC
cases, but it had no significant relationship with SCC staging (p = 0.791).
Immunoreactivity of bcl-2 was observed in 33% of CIN 3 cases. We found a
significant relationship (chi2 test: p = 0.009) between the expression of bcl-2
and CIN grading. Ki-67 index was higher in high grade CIN (HGCIN: CIN 2 and 3)
and SCC lesions compared to normal cervices. Ki-67 index showed a correlation
with bcl-2 protein expression (p = 0.030), but not with p53 protein expression
(p = 0.239). CONCLUSION: HGCIN is an early stage to demonstrate the alteration
of bcl-2 and Ki-67 expressions. Progression of neoplasia in the uterine cervix
is accompanied by an increase of antiapoptotic protein, bcl-2 as well as
cellular proliferation.
------
Akush Ginekol (Sofiia). 2007;46(8):31-5.
[Vaccines for precancer and cancer of the uterine cervix. II.
Therapeutic HPV vaccines]
[Article in Bulgarian]
Kostova P, Zlatkov V.
Gynecology Clinic, National Hospital of Oncology-Sofia.
Vaccines are one of the most powerful immunomodulators and represent perspective
direction in the modern strategy of treatment of cancer. Among the gynecological
malignancies cervical cancer is the most perspective localization for the
implementation of specific therapeutic vaccine, by reason of clear viral
ethiopathogenesis and important medical and social effect of the disease.
Nowadays, the therapeutic HPV vaccines under research, for precancer and cancer
of uterine cervix aimed to eliminate the persistent viral infection. In the
review, the results of several clinical trials concerning the effect of HPV
vaccines, created on the basis of viral peptides, viral like particles, DNA and
viral vectors have been discussed.
------
Gynecol Oncol. 2008 Apr;109(1):86-91. Epub 2008 Feb 14.
Robotic radical hysterectomy: comparison with laparoscopy and
laparotomy.
Magrina JF, Kho RM, Weaver AL, Montero RP, Magtibay PM.
Division of Obstetrics and Gynecology, Mayo Clinic Arizona, 5777 East Mayo
Boulevard, Phoenix, Arizona 85054, USA. jmagrina@mayo.edu
OBJECTIVE: Comparison of perioperative results of patients undergoing radical
hysterectomy by robotics, laparoscopy, and laparotomy. STUDY DESIGN: Prospective
analysis of 27 patients undergoing robotic radical hysterectomy between April
2003 and September 2006. Comparison was made with patients operated by
laparoscopy and laparotomy matched by age, BMI, site and type of malignancy,
FIGO staging, and type of radical hysterectomy. RESULTS: The mean operating
times for patients undergoing robotic, laparoscopy and laparotomy radical
hysterectomy were 189.6, 220.4, and 166.8 min, respectively; the mean blood loss
was 133.1, 208.4, and 443.6 ml, respectively; the mean rate of blood loss was
0.7, 0.9, and 2.6 ml/min, respectively; the mean number of removed lymph nodes
was 25.9, 25.9, and 27.7, respectively; and the mean length of hospital stay was
1.7, 2.4, and 3.6 days, respectively. There were no significant differences in
intra- or postoperative complications among the three groups, no fistula
formation in any patient and no conversions in the robotic or laparoscopic
groups. At a mean follow up of 31.1 months, none of the patients with cervical
cancer has experienced recurrence. CONCLUSION: Laparoscopy and robotics are
preferable to laparotomy for patients requiring radical hysterectomy. Operating
times for robotics and laparotomy were similar, and significantly shorter as
compared to laparoscopy. Blood loss, rate of blood loss and length of hospital
stay were similar for laparoscopy and robotics and significantly reduced as
compared to laparotomy.
-----
Gynecol Oncol. 2008 Apr;109(1):53-8. Epub 2008 Feb 5.
An evaluation of cervical cancer in women age sixty and over.
Fox KV, Shah CA, Swisher EM, Garcia RL, Mandel LS, Gray HJ, Swensen RE, Goff BA.
Department of Obstetrics and Gynecology, University of Washington School of
Medicine, Seattle, Washington 98195, USA. kvfox@u.washington.edu
OBJECTIVE: To assess prior cervical cancer screening, stage at time of diagnosis
and outcome in women sixty years of age and over with cervical cancer. METHODS:
A retrospective review of cervical cancer patients evaluated at the University
of Washington identified a cohort of women age sixty and older with cervical
cancer diagnosed between January 1, 1993 and December 31, 2003. Electronic
medical records and the University of Washington Tumor Registry were reviewed
for age, ethnicity, cervical cancer risk factors, pathology, treatment, and
outcome. RESULTS: Six hundred forty-five women with cervical cancer were
identified. One hundred (15.5%) women were age 60 or older with a median age of
64 years. At time of diagnosis, 41 were early stage (1A1-1B1) and 59 were
advanced stage (1B2-4B). Length of time from last Pap smear significantly
correlated with stage. Radical hysterectomy was performed on 29 patients, and 15
received adjuvant treatment. Forty-nine women received primary
chemo-radiation, and 22 were treated with primary radiation. Lymph node
metastases were identified in 65% of women with locally advanced cervical
cancer. At conclusion of the study period, 80% were alive. Stage and time since
last Pap smear correlated with overall outcome. CONCLUSIONS: Women 60 and older
make up a significant proportion of cervical cancer patients, often fail to
receive screening, present with locally advanced disease, and tolerate standard
treatment protocols. Careful consideration of these findings should be made when
establishing Pap smear screening guidelines for this population of women.
-----
Gynecol Oncol. 2008 Apr;109(1):43-8. Epub 2008 Jan 29.
Survival for stage IB cervical cancer with positive lymph node
involvement: a comparison of completed vs. abandoned radical hysterectomy.
Richard SD, Krivak TC, Castleberry A, Beriwal S, Kelley JL 3rd, Edwards RP,
Sukumvanich P.
Division of Gynecologic Oncology, Magee-Womens Hospital, 300 Halket Street,
Pittsburgh, PA 15213, USA.
PURPOSE: Management for stage IB cervical cancer with intraoperative positive
pelvic lymph nodes (LNs) is controversial. We compare 5-year survival rates for
women with completed vs. abandoned radical hysterectomy (RH) who were treated
with postoperative radiation therapy (RT). PATIENTS AND METHODS: We identified
all women diagnosed with stage IB cervical carcinoma from the Surveillance,
Epidemiology, and End Results database from 1988-1998. Women with positive LN
involvement who had undergone a complete pelvic and para-aortic lymphadenectomy
were compared for 5-year survival based on whether a RH was completed or
abandoned at the time of surgery. All women then received postoperative RT.
Survival rates were calculated using the Kaplan-Meier method, and the Chi square
test was used for all univariate analysis. RESULTS: From a cohort of 3116 women
diagnosed with stage IB cervical cancer, 265 (8.7%) had positive pelvic LNs and
a complete pelvic and para-aortic lymphadenectomy. Of these women, 163 had
completion of their RH while RH was abandoned in 55. Positive pelvic LNs
averaged 2.58+/-2.37 in the completed RH group and 2.42+/-1.63 in the abandoned
RH group. Median follow-up was 6.42 years in the completed RH group and 5.75
years in the abandoned RH group. Five-year survival for the completed RH group
was 69% compared with 71% in patients with abandoned RH (p=0.46). CONCLUSIONS:
Treatment for patients with positive pelvic LNs at the time of RH should be
determined by overall morbidity of therapy since equivalent 5-year survival was
found between the completed and abandoned RH groups.
-----
Histopathology. 2008 Feb;52(3):381-6.
Natural history and clearance of HPV after treatment of
precancerous cervical lesions.
Aerssens A, Claeys P, Garcia A, Sturtewagen Y, Velasquez R, Vanden Broeck D,
Vansteelandt S, Temmerman M, Cuvelier CA.
International Centre for Reproductive Health, Ghent University, Ghent, Belgium.
AIM: To assess the clearance rate of human papillomavirus (HPV) after
out-patient treatment of cervical intraepithelial neoplasia (CIN). METHODS AND
RESULTS: A total of 122 Nicaraguan women with HPV DNA-positive and
histologically confirmed CIN lesions were included in the study. Fifty-five
patients with CIN1 and 67 with CIN2-3 were treated by cryotherapy and loop
electrosurgical excision procedure (LEEP), respectively. Follow-up visits were
scheduled at 6 weeks, 6 months, 1 year and 2 years. Investigations included
cytology, HPV DNA testing and colposcopy/biopsy if needed. The clearance rate of
HPV was calculated by multivariate logistic regression. Immediately after
treatment, a pronounced decrease in presence of HPV was observed in both groups,
with a significantly higher clearance in the LEEP group than in the cryotherapy
group (P = 0.019). Subsequently, clearance continued over time and was similar
between the cryotherapy group and the LEEP group (P = 0.73). Approximately the
same detection rates were obtained for persistence of all HPV types and for
high-risk types separately: 43.9, 37.6, 29.9 and 17.7% in the cryotherapy group
and 24.9, 20.3, 15.3 and 8.4% in the LEEP group at 6 weeks, 6 months, 1 year and
2 years, respectively. CONCLUSIONS: Out-patient treatment of precancerous
lesions of the cervix usually results in clearance of HPV. Both LEEP and
cryotherapy are highly effective methods of eradicating HPV. HPV DNA testing may
have added value in the follow-up of patients.
-----
Mo Med. 2008 Jan-Feb;105(1):8-11.
HPV vaccine mandates: just say 'no' to the "great big public
health experiment".
Onder RF.
Washington University School of Medicine, St. Louis, USA. Bob.Onder@house.mo.gov
While many states are seriously considering requiring vaccination of pre-teen
girls as a condition of middle school admission, the case for mandatory human
papillomavirus (HPV) vaccine is very weak. Such a requirement lacks the
traditional justification for vaccine mandates and therefore represents an
unjustified usurpation of parental authority. Moreover, serious questions remain
as to whether the vaccine is effective in preventing cervical cancer. The
vaccine is the most expensive pediatric vaccine in history. Given the
uncertainties surrounding the vaccine, Missouri lawmakers and taxpayers should
reject this expensive and intrusive "public health experiment".
-----
J Natl Compr Canc Netw. 2008 Jan;6(1):101-6.
Conservative management of adolescents with abnormal cytology and
histology.
Moscicki AB.
Division of Adolescent Medicine, University of California San Francisco, 3333
California Street, Suite 245, San Francisco, CA 94118, USA. moscickia@peds.ucsf.edu
Adolescents remain vulnerable to human papilloma virus (HPV) infection because
of certain physiologic characteristics inherent in this age group and common
sexual behaviors, including lack of condom use. The commonness of HPV in this
age group also results in frequent abnormal cytology. Fortunately, most of the
infections are transient, with frequent clearance of HPV and the lesion. Current
strategies for adolescents with abnormal cytology include conservative
management, avoiding invasive procedures. For cytologic atypical squamous cells
of undetermined significance or squamous intraepithelial lesions (SIL),
management can be obtaining cytology only at 1-year intervals for up to 2 years
before referral for colposcopy is necessary. For biopsy-proven cervical
intraepithelial neoplasia (CIN) I, management is similar with yearly cytology
indefinitely or until high-grade-SIL or CIN II/III develops. CIN II in adherent
adolescents can be managed with 6-month cytology and colposcopy.
-----
J Natl Compr Canc Netw. 2008 Jan;6(1):53-7.
Chemotherapy for advanced, recurrent, and metastatic cervical
cancer.
Moore DH.
Gynecologic Oncology of Indiana, 5255 East Stop 11 Road, Suite 310,
Indianapolis, IN 46237, USA. David.Moore@ssfhs.org
When cervical cancer is beyond curative treatment with surgery or radiation
therapy, the prognosis is poor and palliation is the primary objective. Early
prospective studies identified cisplatin as an active drug for advanced,
metastatic, or recurrent cervical cancer, and results with other platinum
analogs seemed inferior to cisplatin. Several phase III trials have established
the combination of cisplatin plus paclitaxel as standard therapy for comparison.
Using pooled data from 3 Gynecologic Oncology Group (GOG) phase III studies, a
predictive model was developed to better identify patients who are unlikely to
respond to cisplatin-containing chemotherapy. The GOG is currently developing a
phase III trial to investigate the impact of bevacizumab and a regimen
containing topotecan instead of cisplatin in combination with paclitaxel
chemotherapy and also to externally validate the predictive model. This study
has the potential to radically change standard care for cervical cancer
chemotherapy. Furthermore, if the predictive model is upheld, then patients with
high risk factors for treatment failure may be directed to chemotherapy regimens
that do not include cisplatin or to investigational trials.
-----
J Natl Compr Canc Netw. 2008 Jan;6(1):47-52.
Primary management of early stage cervical cancer (IA1-IB) and
appropriate selection of adjuvant therapy.
Gray HJ.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Box
356460, University of Washington School of Medicine, Seattle, WA 98195, USA.
hgray@u.washington.edu
Cervical cancer is the third most common gynecologic malignancy in the United
States but the leading gynecologic cancer worldwide. Most patients will present
with clinical early-stage disease (International Federation of Gynecology and
Obstetrics [FIGO] stage IA1-IB). These patients are a clinically heterogeneous
group, and primary treatment can be either surgery or radiotherapy. Standard
surgery is either radical hysterectomy with lymphadenectomy (stage IA2-IB2) or
simple hysterectomy for microinvasive disease (stage IA1). Interest has been
increasing in using conservative fertility-sparing surgery through radical
trachelectomy as an option for select patients with early-stage disease who want
future fertility. Primary radiotherapy is delivered as a combination of
external-beam teletherapy and brachytherapy. It is given with concurrent
cisplatin-based chemotherapy, based on 5 large randomized controlled trials that
showed significant improvement in overall survival with the addition of
chemotherapy. Using either radical surgery or radiation therapy in stage IB
disease yields 5-year survival rates of 87% to 92%. The addition of
postoperative adjuvant radiation with concurrent chemotherapy is recommended in
patients with high- or intermediate-risk disease after radical hysterectomy to
reduce risk for recurrence and improve progression-free survival. In select
patients with stage IB2 disease with bulky tumors undergoing primary
chemoradiation, adjuvant hysterectomy may provide benefit after treatment.
-----
Am J Obstet Gynecol. 2007 Dec;197(6):566-71.
Reducing the burden of glandular carcinomas of the uterine cervix.
Herzog TJ, Monk BJ.
Columbia University, Irving Comprehensive Cancer Center, New York Presbyterian
Hospital, New York, NY, USA.
Widespread use of the Papanicolaou test for the screening of cervical cancers
has lead to a significant decline in overall incidence and mortality rates over
the past 3 decades. When different histologic types of cervical cancers are
considered and trends are reexamined, it becomes apparent that observed declines
are reflective of squamous cell carcinomas predominantly; the rates for
adenocarcinomas continue to rise. This rise in incidence may be due to the
greater difficulty in screening for glandular precursor lesions that often arise
high within the endocervical canal. Reducing the incidence and mortality rates
that are associated with adenocarcinomas can be accomplished by using improved
screening techniques and large-scale implementation of cervical cancer vaccines
that target the predominant oncogenic human papillomavirus types that are
associated with adenocarcinoma.
-----
Obstet Gynecol. 2007 Dec;110(6):1237-43.
Adjuvant radiotherapy in incompletely staged IC and II endometrioid uterine
cancer.
Parthasarathy A, Kapp DS, Cheung MK, Shin JY, Osann K, Chan JK.
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of
California, San Francisco, California 94143-1702, USA.
OBJECTIVES: To estimate if adjuvant radiotherapy improves the disease-specific
survival of patients with clinical stage IC and II endometrioid corpus cancer
who did not undergo lymphadenectomy. METHODS: Information was obtained on
patients with endometrioid corpus cancer from the National Cancer Institute
database between 1988 and 2001. Data were analyzed using Kaplan-Meier and Cox
proportional hazards regression methods. RESULTS: A total of 3,664 patients
(median age 70 years) with clinical stage IC to II endometrioid carcinoma did
not undergo lymphadenectomy, of which 2,170 had stage IC and 1,494 stage II
disease. Of these, 1,175 had grade 1, 1,637 had grade 2, 693 had grade 3, and in
159, grade was unknown. The 5-year disease-specific survival rates of clinical
stage IC compared with stage II patients were 91.3% and 86.7% (P<.001). Of the
1,964 who received adjuvant radiotherapy, the 5-year disease-specific survival
rate was 89.9% compared with 87.8% in those who did not undergo further
treatment (P=.04). Adjuvant radiation improved the disease-specific survival
rate of those with stage II disease, (86.5% compared with 81.9%; P=.02), but not
in those with stage IC disease (91.7% compared with 92.6%; P=.68). The benefit
of radiotherapy was significant in patients with grade 3 disease and patients 70
years or older (88.2% compared with 83.3%; P<.001). On multivariable analysis,
age, stage, and grade were significant independent prognostic factors for
disease-specific survival. CONCLUSION: Adjuvant radiotherapy marginally improved
the survival of clinically staged IC-II endometrioid uterine cancer patients
without lymphadenectomy. After excluding those without hysterectomy,
radiotherapy did not significantly affect disease-specific survival. LEVEL OF
EVIDENCE: II.
-----
J Minim Invasive Gynecol. 2007 Nov-Dec;14(6):698-705.
Robot-assisted laparoscopic myomectomy versus abdominal myomectomy: a comparison
of short-term surgical outcomes and immediate costs.
Advincula AP, Xu X, Goudeau S 4th, Ransom SB.
Department of Obstetrics and Gynecology, University of Michigan Medical Center,
Women's Hospital, Ann Arbor, MI 48109, USA. aadvincu@umich.edu
STUDY OBJECTIVE: To compare surgical outcomes of myomectomy by robot-assisted
laparoscopy with those performed by traditional laparotomy and to analyze the
financial impact of these 2 approaches. DESIGN: Retrospective case-matched
analysis (Canadian Task Force classification III). SETTING: University teaching
hospital. PATIENTS: A total of 58 patients with symptomatic leiomyomata.
INTERVENTION: Myomectomy by robot-assisted laparoscopy or traditional laparotomy
was administered. MEASUREMENTS AND MAIN RESULTS: An equal number of case-matched
patients based on age, body mass index, and myoma weight were analyzed in each
group. Among these 3 variables, there were no statistically significant
differences between the robotic and laparotomy groups. Mean age was 36.59 +/-
4.93 years (95% CI 34.71-38.46 years) versus 34.86 +/- 4.41 years (95% CI
33.18-36.54 years), mean body mass index was 25.22 +/- 3.85 kg/m(2) (90% central
range [CR] 20.30-31.20 kg/m2) versus 28.3 +/- 6.95 kg/m2 (90% CR 21.50-42.80
kg/m2), and mean myoma weight was 227.86 +/- 247.54 g (90% CR 11.60-680.00 g)
versus 223.76 +/- 228.28 g (90% CR 11.50-660.00 g), respectively. Patients with
robot-assisted laparoscopic myomectomy had decreased estimated blood loss (mean
195.69 +/- 228.55 mL [90% CR 50.00-700.00 mL] vs mean 364.66 +/- 473.28 mL [90%
CR 75.00-1550.00 mL]) and length of stay (mean 1.48 +/- 0.95 days [90% CR
1.00-3.00 days] vs mean 3.62 +/- 1.50 days [90% CR 3.00-8.00 days]) when
compared with the laparotomy group. Both of these differences were statistically
significant at p <.05. Operative times were significantly longer in the robotic
group: mean 231.38 +/- 85.10 minutes (95% CI 199.01-263.75 minutes) versus mean
154.41 +/- 43.14 minutes (95% CI 138.00-170.82 minutes, p <.05) in the
laparotomy group. Complication rates were higher in the laparotomy group.
Professional charges (mean $5946.48 +/- $1447.17 [90% CR $4034.46-$8937.00] vs
mean $4664.48 +/- $642.11 [90% CR $3944.36-$6010.90, p <.0002]) and hospital
charges (mean $30084.20 +/- $6689.29 [90% CR $22939.81-$45588.22] vs mean
$13400.62 +/- $7747.26 [90% CR $8703.20-$26771.22, p <.0001]) were statistically
higher for the robotic group. Although professional reimbursement was not
significantly different between groups (mean $2263.02 +/- $1354.97 [90% CR
$0.00- $4831.08] versus mean $1841.99 +/- $827.51 [90% CR $0.00-$3376.97, p =
.2831]), mean hospital reimbursement rates for the robotic group were
significantly higher: $13181.39 +/- $10752.00 (90% CR $1081.76-$37396.03) versus
$7015.24 +/- $3467.97 (90% CR $2492.48-$10394.83, p = .0372). CONCLUSION: As a
new technology, it is not unexpected that a robotic approach to myomectomy costs
more than a traditional laparotomy. On the other hand, decreased estimated blood
loss, complication rates, and length of stay with the robotic approach in the
end may prove to have a significant societal benefit that will outweigh upfront
financial impact.
-----
Gynecol Oncol. 2007 Nov;107(2 Suppl):S27-30.
Long-term efficacy of human papillomavirus vaccination.
Ault KA.
Division of Gynecologic Oncology, Department of Gynecology and Obstetrics, Emory
University School of Medicine, 69 Jesse Hill Drive, Atlanta, GA 30064, USA.
kevin.ault@emory.edu
Achieving long-term protection following vaccination is crucial to ensuring that
high levels of immunity are maintained within a population while eliminating the
need to introduce booster vaccinations. Based on an analysis of the hepatitis B
virus vaccine, several factors have been shown to contribute to long-term
protection, namely: specific lymphoproliferation, the in vivo humoral response,
and immune memory. To ensure protection against persistent human papillomavirus
(HPV) infection and the subsequent development of cervical lesions, an effective
HPV vaccine must be able to induce strong humoral immune responses. Mathematical
modeling analyses based on a three-dose regimen of HPV type 16 prophylactic
vaccine indicated that 99% of 16- to 23-year-old women would have almost
life-long detectable anti-HPV-16 levels. Available data on the quadrivalent HPV
vaccine demonstrated that long-term immune memory was induced, with anti-HPV
geometric mean titers after 5 years remaining at or above those observed with
natural infection. Vaccination also resulted in a substantial reduction in the
combined incidence of HPV-6/11/16/18 related persistent infection or disease,
and there were no cases of precancerous cervical dysplasia compared with six
cases in women receiving placebo. Similarly the bivalent HPV vaccine has been
shown to induce long-term immunity with >98% seropositivity maintained after 4.5
years of follow-up and geometric mean titres at this time point remaining
substantially higher than those noted with naturally acquired infection.
Countrywide registration regarding population and health events in a stable
population of approximately 25 million makes the Nordic countries an ideal
setting for the evaluation of long-term cervical cancer control.
Population-based long-term efficacy trials conducted in these countries aim to
investigate the long-term efficacy of HPV vaccination with regard to invasive
cervical cancer, and the results of these trials are awaited with interest.
-----
Gynecol Oncol. 2007 Nov;107(2 Suppl):S19-23.
Prevention strategies against the human papillomavirus: the effectiveness of
vaccination.
Stanley M.
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge
CB2 1QP, UK. mas@mole.bio.cam.ac.uk
It has been clearly established that sexually transmitted human papillomavirus (HPV)
infections are the major cause of genital warts and cervical cancer and are a
contributing factor in the development of other types of anogenital cancers.
There is a higher risk of HPV infection with an increasing number of sexual
partners. Health education measures aimed at improving the use of condoms,
reducing the number of sexual partners and promoting safer sex strategies have
been employed with the goal of decreasing the transmission of HPV. Of these
intervention strategies, promotion of condom use has been shown to be the most
effective. More recently, prophylactic HPV vaccines have been developed with the
aim of reducing the burden of HPV-related diseases such as cervical cancer. Two
vaccines have been developed: Gardasil, a quadrivalent vaccine targeting HPV-6,
-11, -16 and -18) and Cervarix, a bivalent vaccine which targets HPV-16 and -18.
HPV-16 and -18 are most commonly associated with cervical cancer. In clinical
trials, HPV vaccination has been shown to be safe, immunogenic and highly
effective against type-specific HPV infection. Predictive data also indicate
that the implementation of HPV vaccination within a national screening program
is likely to be cost-effective relative to current clinical practice.
-----
Am J Obstet Gynecol. 2007 Nov;197(5):503.e1-6.
Comment in:
Am J Obstet Gynecol. 2007 Nov;197(5):443-4.
Radiation therapy with or without weekly cisplatin for bulky stage 1B cervical
carcinoma: follow-up of a Gynecologic Oncology Group trial.
Stehman FB, Ali S, Keys HM, Muderspach LI, Chafe WE, Gallup DG, Walker JL,
Gersell D.
Department of Obstetrics and Gynecology, Indiana University School of Medicine,
Indianapolis, IN 46202, USA. fstehman@iupui.edu
OBJECTIVE: The objective of the study was to confirm that concurrent cisplatin
(CT) with radiation therapy (RT) is associated with improved long-term
progression-free survival (PFS) and overall survival (OS), compared with RT
alone in stage IB bulky carcinoma of the cervix, when both groups' therapy is
followed by hysterectomy. STUDY DESIGN: Three hundred seventy-four patients
entered this trial. There were 369 evaluable patients; 186 were randomly
allocated to receive RT alone and 183 to receive CT plus RT. Radiation dosage
was 45 Gray (Gy) in 20 fractions followed by low dose-rate intracavitary
application(s) of 30 Gy to point A. Chemotherapy consisted of intravenous
cisplatin 40 mg/m2 every week for up to 6 weekly cycles. Total extrafascial
hysterectomy followed the completion of RT by 6-8 weeks. RESULTS: Preliminary
results have been published, at which time there were 292 censored observations,
and median duration of follow-up was only 36 months. Patient and tumor
characteristics were well balanced between the regimens. The median patient age
was 41.5 years; 81% had squamous tumors; 59% were white. Median follow-up is now
101 months. The relative risk for progression was 0.61 favoring CT plus RT (95%
confidence interval [CI] 0.43 to 0.85, P < .004). At 72 months, 71% of patients
receiving CT plus RT were predicted to be alive and disease free when adjusting
for age and tumor size, compared with 60% of those receiving RT alone. The
adjusted death hazard ratio was 0.63 (95% CI 0.43 to 0.91, P < .015) favoring CT
plus RT. At 72 months, 78% of CT plus RT patients were predicted to be alive,
compared with 64% of RT patients. An increased rate of early hematologic and
gastrointestinal toxicity was seen with CT plus RT. There was no detectable
difference in the frequency of late adverse events. CONCLUSION: Concurrent
weekly cisplatin with RT significantly improves long-term PFS and OS when
compared with RT alone. Serious late effects were not increased. The inclusion
of hysterectomy has been discontinued on the basis of another trial. Pending
further trials, weekly cisplatin with radiation is the standard against which
other regimens should be compared.
-----
BMJ. 2007 Nov 24;335(7629):1077. Epub 2007 Oct 24.
Comment in:
BMJ. 2007 Nov 24;335(7629):1053-4.
Long term risk of invasive cancer after treatment for cervical intraepithelial
neoplasia grade 3: population based cohort study.
Strander B, Andersson-Ellström A, Milsom I, Sparén P.
Department of Obstetrics and Gynecology, Sahlgren's Academy, University of
Gothenburg, SU/Ostra sjukhuset, SE-416 85, Sweden. bjorn.strander@oc.gu.se
OBJECTIVE: To study the long term risk of invasive cancer of the cervix or
vagina after treatment for cervical intraepithelial neoplasia grade 3. DESIGN:
Prospective cohort study. SETTING: Swedish cancer registry. PARTICIPANTS: All
women in Sweden with severe dysplasia or cervical carcinoma in situ (equivalent
to cervical intraepithelial neoplasia grade 3) treated during 1958-2002
(n=132,493) contributing 2,315,724 woman years. MAIN OUTCOME MEASURES:
Standardised incidence ratios with risk of cancer in the Swedish general female
population as reference, and relative risks in multivariable log-linear
regression model, with internal references. RESULTS: Women with previous
cervical intraepithelial neoplasia grade 3 had an increased risk of invasive
cervical cancer compared with the general female population (standardised
incidence ratio 2.34, 95% confidence interval 2.18 to 2.50). The increased risk
showed a decreasing trend with time since diagnosis for women treated later than
1970 but the risk was still increased after 25 years. An effect of age was
found, with an accentuated increase in risk for women aged more than 50. The
excess risk for cervical cancer associated with previous cervical
intraepithelial neoplasia grade 3 has steadily increased since 1958. For vaginal
cancer the standardised incidence ratio was 6.82 (5.61 to 8.21) but this
decreased to 2.65 after 25 years. Adjustments in the multivariable log-linear
regression model did not substantially alter these results. CONCLUSIONS: Women
previously treated for cervical intraepithelial neoplasia grade 3 are at an
increased risk of developing invasive cervical cancer and vaginal cancer. This
risk has increased since the 1960s and is accentuated in women aged more than
50. The risk is still increased 25 years after treatment.
-----
Anticancer Res. 2007 Sep-Oct;27(5B):3525-8.
Bevacizumab therapy in patients with recurrent uterine neoplasms.
Wright JD, Powell MA, Rader JS, Mutch DG, Gibb RK.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology,
Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
jw2459@columbia.edu
BACKGROUND: Angiogenesis plays an important role in endometrial carcinogenesis.
We reviewed our experience with the anti-VEGF monoclonal antibody bevacizumab
for the treatment of recurrent uterine neoplasms. PATIENTS AND METHODS: A
retrospective analysis of women with recurrent uterine neoplasms treated with
bevacizumab was performed. RESULTS: A total of 11 patients were identified, 9
with epithelial endometrial carcinomas and 2 with leiomyosarcomas. All patients
had multi-site disease and were heavily pretreated with a median of 3 prior
chemotherapy regimens. All received bevacizumab combination therapy which was
well-tolerated. Two patients had partial responses, 3 had stable disease, while
5 patients progressed. One subject was not assessable for response. The median
progression-free interval was 5.4 months for the entire cohort and 8.7 months
for those who achieved clinical benefit (PR or SD). CONCLUSION: Bevacizumab was
well-tolerated and displayed promising anti-neoplastic activity in patients with
endometrial cancer and uterine leiomyosarcoma.
-----
Bull World Health Organ. 2007 Sep;85(9):719-26.
Human papillomavirus and HPV vaccines: a review.
Cutts FT, Franceschi S, Goldie S, Castellsague X, de Sanjose S, Garnett G,
Edmunds WJ, Claeys P, Goldenthal KL, Harper DM, Markowitz L.
Initiative for Vaccine Research, WHO, Geneva, Switzerland.
felicity.cutts@lshtm.ac.uk
Cervical cancer, the most common cancer affecting women in developing countries,
is caused by persistent infection with "high-risk" genotypes of human
papillomaviruses (HPV). The most common oncogenic HPV genotypes are 16 and 18,
causing approximately 70% of all cervical cancers. Types 6 and 11 do not
contribute to the incidence of high-grade dysplasias (precancerous lesions) or
cervical cancer, but do cause laryngeal papillomas and most genital warts. HPV
is highly transmissible, with peak incidence soon after the onset of sexual
activity. A quadrivalent (types 6, 11, 16 and 18) HPV vaccine has recently been
licensed in several countries following the determination that it has an
acceptable benefit/risk profile. In large phase III trials, the vaccine
prevented 100% of moderate and severe precancerous cervical lesions associated
with types 16 or 18 among women with no previous infection with these types. A
bivalent (types 16 and 18) vaccine has also undergone extensive evaluation and
been licensed in at least one country. Both vaccines are prepared from
non-infectious, DNA-free virus-like particles produced by recombinant technology
and combined with an adjuvant. With three doses administered, they induce high
levels of serum antibodies in virtually all vaccinated individuals. In women who
have no evidence of past or current infection with the HPV genotypes in the
vaccine, both vaccines show > 90% protection against persistent HPV infection
for up to 5 years after vaccination, which is the longest reported follow-up so
far. Vaccinating at an age before females are exposed to HPV would have the
greatest impact. Since HPV vaccines do not eliminate the risk of cervical
cancer, cervical screening will still be required to minimize cancer incidence.
Tiered pricing for HPV vaccines, innovative financing mechanisms and
multidisciplinary partnerships will be essential in order for the vaccines to
reach populations in greatest need.
-----
Lancet Oncol. 2007 Sep;8(9):831-41.
Role of complete lymphadenectomy in endometrioid uterine cancer.
Chan JK, Kapp DS.
Division of Gynecologic Oncology, University of California, San Francisco
Comprehensive Cancer Center, Department of Obstetrics, Gynecology, and
Reproductive Sciences, University of California, San Francisco School of
Medicine, San Francisco, CA, USA.
Although surgical pathological staging is the standard of care for uterine
carcinoma, the benefits of a complete lymphadenectomy remain controversial.
Evidence suggests that this procedure provides prognostic information and
directs the use of appropriate adjuvant treatment in patients who are
node-positive. Furthermore, it eliminates the need for adjuvant treatment in
low-risk patients with negative nodes and no extrauterine spread of disease.
Although the complications associated with this procedure raise the question as
to whether all low-risk patients need a complete lymphadenectomy, the
limitations of preoperative and intraoperative pathological analyses mean that
lymphadenectomy in low-risk patients might still have merit. Future advances are
warranted to enhance preoperative radiological and intraoperative pathological
assessment to establish the risk of nodal disease. In this review, we assess the
evidence on the prognostic and therapeutic benefits of a complete versus
selective lymphadenectomy. Moreover, we discuss the complications associated
with lymphadenectomy and identify subsets of low-risk patients who might not
need to undergo this procedure.
-----
Clin Infect Dis. 2007 Sep 1;45(5):609-7. Epub 2007 Jul 25.
Quadrivalent human papillomavirus vaccine.
Barr E, Tamms G.
Merck Research Laboratories, West Point, PA, USA. eliav_barr@merck.com
The lifetime risk of human papillomavirus (HPV) infection exceeds 50%. HPV
infection causes >550,000 cases of cervical and anogenital cancer worldwide
annually. Infection also causes precancerous lesions and genital warts. HPV
types 16 and 18 cause approximately 70% of HPV-related cancers, and HPV types 6
and 11 cause approximately 90% of cases of genital warts. A quadrivalent vaccine
for HPV types 6, 11, 16, and 18 (HPV 6/11/16/18) has been developed for
prevention of cervical cancer, genital warts, and vulvar and vaginal
precancerous lesions. Prophylactic vaccination of young women was 96%-100%
effective in preventing HPV 6/11/16/18-related cervical and anogenital
precancers and genital warts. Efficacy remained high for at least 5 years
following vaccination. Postvaccination anti-HPV levels in adolescents were
superior to those observed in women (the population in which efficacy was
shown). Vaccination was generally well tolerated. The vaccine is licensed in >80
countries. It has been added to national vaccination programs, including that of
the United States. Widespread use of HPV 6/11/16/18 vaccine is expected to
greatly reduce the incidence of HPV-related cancers, precancers, and genital
warts.
-----
Am J Obstet Gynecol. 2007 Aug;197(2):205.e1-5; discussion 205.e5-7.
Concurrent carboplatin and paclitaxel with pelvic radiation
therapy in the primary treatment of cervical cancer.
Higgins R, Bussey M, Naumann W, Hall J, Tait D, Haake M.
Department of Obstetrics and Gynecology, Carolinas Medical Center, Charlotte,
NC, USA.
OBJECTIVE: The objective of the study was to determine the feasibility of weekly
carboplatin/paclitaxel with radiation therapy (RT) in the primary treatment of
cervical cancer. STUDY DESIGN: Women diagnosed with stage IB-1 to stage IVA
untreated primary cervical cancer were eligible. Carboplatin (area under the
curve = 2.0) and paclitaxel 40 mg/m2 were administered weekly for 6 weeks with
pelvic RT. Brachytherapy was completed after pelvic RT. Acute toxicities and
response to treatment were assessed. RESULTS: Twenty-two evaluable patients were
enrolled. The median duration of follow-up was 23 months. Carboplatin (mean dose
245 mg) and paclitaxel (mean dose 70 mg) were successfully administered in 97%
and 90% of planned treatments, respectively. Median time to complete external
radiation therapy was 36.6 days (25-57 days). Grade 3/4 hematologic or
gastrointestinal toxicity was unusual. The complete response rate 3 months after
completion of therapy was 91%. The estimated 3-yea
r progression-free survival is 70% and overall survival is 65%. CONCLUSION:
Weekly carboplatin/paclitaxel and RT is a reasonable treatment regimen for
cervical cancer.
-----
Gynecol Oncol. 2007 Aug;106(2):282-8.
The outcomes of 27,063 women with unstaged endometrioid uterine
cancer.
Chan JK, Wu H, Cheung MK, Shin JY, Osann K, Kapp DS.
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of
California, San Francisco School of Medicine, University of California, San
Francisco Comprehensive Cancer Center, San Francisco, CA 94143, USA. chanjohn@obgyn.ucsf.edu
BACKGROUND: Over two-thirds of patients with endometrioid uterine cancer in the
Surveillance, Epidemiology and End Results program from 1988 to 2001 did not
undergo a lymphadenectomy. These patients were compared to those who had a
lymphadenectomy. METHODS: Kaplan-Meier methods and Cox proportional hazards
regression analyses were employed. RESULTS: Of 39,396 women (median age: 65
years) with endometrioid uterine cancers, 12,333 (31.3%) underwent surgical
staging procedures including lymphadenectomy. The remainder did not receive a
lymphadenectomy. The 5-year disease-specific survival (DSS) of stages I-IV women
who underwent lymphadenectomy were 95.5%, 90.4%, 73.8%, and 53.3% compared to
96.6%, 82.2%, 63.1%, and 26.9% in those without lymphadenectomy (p>0.05 for
stage I; p<0.001 for stages II-IV). In stage I patients, those who did not
receive lymphadenectomy had a higher proportion of tumors with grade 1 histology
and/or disease limited to the endometrium compared to those who underwent
lymphadenectomy (54.8 % vs. 34.7%; p<0.001, grade 1 disease; 26.6% vs. 15.9%;
p<0.001, no myometrial invasion). In patients with stage I grade 3 disease,
those who underwent lymphadenectomy had a better 5-year DSS than those without
lymphadenectomy (90% vs. 85%; p=0.0001); however, no benefit for lymphadenectomy
was seen for patients with stage I grade 1 (p=0.26) and grade 2 (p=0.14)
disease. On multivariable analysis, younger age, Caucasian race, early-stage
disease, low grade histology, and lymphadenectomy were independent prognostic
factors for improved disease-specific survival. CONCLUSIONS: Our data suggest
that lymphadenectomy is associated with an improved survival in stage I grade 3
and more advanced endometrioid uterine cancers.
-----
J Minim Invasive Gynecol. 2007 Jul-Aug;14(4):453-62.
Italian multicenter study on complications of laparoscopic
myomectomy.
Sizzi O, Rossetti A, Malzoni M, Minelli L, La Grotta F, Soranna L, Panunzi S,
Spagnolo R, Imperato F, Landi S, Fiaccamento A, Stola E.
Villa Valeria Hospital, Rome, Italy. ornella.sizzi@alfamedica.it
STUDY OBJECTIVE: To study intraoperative and postoperative complications of
laparoscopic myomectomy and patients' characteristics influencing this risk.
DESIGN: Prospective study, with a review of the patient records by the first
author (Canadian Task Force classification II-2). SETTING: Four Italian referral
centers. PATIENTS: The incidence and type of complications occurring in 2050
laparoscopic myomectomies undertaken from January 1998 through December 2004
were recorded. INTERVENTIONS: The surgical technique, as well as the expertise
of the operators, was the same for the 4 centers. Injection of vasoconstrictive
agents was used in 37%. The serosa was always incised in a vertical fashion;
mechanical enucleation of the myoma was completed whenever possible; suture was
performed in 1 or 2 layers with deep and large stitches swaged to 1 or 0
polyglactin sutures that were tied intracorporeally or extracorporeally.
MEASUREMENTS AND MAIN RESULTS: Single or multiple myomectomies (n = 2050) for
symptomatic myomas measuring at least 4 cm in diameter were performed. Most
patients (48%) had more than 1 myoma, with a maximum of 15 per patient (myomas
removed for patients: 2.26 +/- 1.8, mean +/- SD). Myoma size ranged from 1 to 20
cm (mean 6.40 +/- 2.6 SD). Myomas smaller than 4 cm were removed during
myomectomy for larger ones. Total complication rate was 11.1% (225/2050 cases).
Minor complications accounted for 9.1% (187/2050 cases) and major complications
for 2.02% (38/2050 cases). The most serious events were hemorrhages (14 cases,
0.68%) requiring blood transfusions in 3 cases (0.14%); 10 postoperative
hematomas (0.48%, one in the broad ligament and 9 in the myomectomy scar); 1
bowel injury (0.04%); 1 postoperative acute kidney failure (0.04%); and 2
unexpected sarcomas (0.09%). Failure to complete planned surgery occurred in 7
cases (0.34%). Two patients were readmitted for surgery (0.09%): 1 had a
laparoscopic hysterectomy because of a severe blood loss, and the other had
drainage of a hematoma in the broad ligament. After a follow-up period of 41.70
+/- 23.03 months (mean +/- SD), 386 (22.9%) patients conceived, with a pregnancy
rate in patients wishing pregnancy of 69.8%; among them, 1 (0.26%) recorded
spontaneous uterine rupture at 33 weeks gestation. Odds ratio computed to
estimate the risk of complications in relation to the patient characteristics
showed that the probability of complications significantly rises with an
increase in the number (more than 3 myomas OR: 4.46, p <.001) and with the
intramural (OR: 1.48, p <.05) or the intraligamentous location of myomas (OR:
2.36, p <.01) whereas the myoma size seems to influence particularly the risk of
major complications (OR: 6.88, p <.001). CONCLUSIONS: This is one of the largest
series reported of laparoscopic myomectomy and the first focused on
complications. The complication rate appears to be better than acceptable in
comparison with complication rates reported after laparotomic myomectomies.
Laparoscopic myomectomy, when performed by an experienced surgeon, can be
considered a safe technique with an extremely low failure rate and good results
in terms of pregnancy outcome.
-----
J Minim Invasive Gynecol. 2007 Jul-Aug;14(4):449-52.
Total laparoscopic hysterectomy with and without lymph node
dissection for uterine neoplasia.
O'Hanlan KA, Pinto RA, O'Holleran M.
Gynecologic Oncology Associates and Sequoia Hospital, Portola Valley, California
94028, USA. ohanlan@aol.com
STUDY OBJECTIVE: To compare surgical outcomes of patients with uterine neoplasia
undergoing total laparoscopic hysterectomy only (TLH) with those having TLH and
lymph node dissection (TLHND) from September 5, 1996 through January 13, 2007.
DESIGN: Retrospective chart analysis (Canadian Task Force classification II-2).
SETTING: Three tertiary surgical centers in California. PATIENTS: 112 patients
with uterine neoplasia operated on from 1996 through 2006. INTERVENTIONS: All
patients underwent total laparoscopic hysterectomy and bilateral
salpingoophorectomy; however, 30 patients with FIGO stage IC or higher, lymph
channel involvement, or grade 3 disease also underwent pelvic and aortic node
dissection. MEASUREMENTS AND MAIN RESULTS: Of 807 patients having TLH, 112 had a
uterine neoplasia: twenty-one hyperplasia, 86 carcinoma, 2 ovarian and
endometrial carcinoma, and 3 low-grade endometrial stromal sarcoma; 82 had TLH
and adnexectomy; and 30 had TLHND. For both groups, the mean age was 60 (NS),
Quatlet index was 31.2 (NS), parity was 1.6 (NS), and the mean blood loss was
148 mL (NS). The node dissection added 56 minutes to TLH (132 vs 188 minutes, p
<.001) and yielded a mean of 25 nodes. Patients in both groups spent a median of
1 day in the hospital (NS). There were 7 complications (6.3%) in the series:
among the patients in the TLH group, 1 conversion to laparotomy for bleeding
from an ovarian artery, 1 vaginal rupture during coitus at 6 weeks, and 1
nonsurgical episode of diverticulitis. There were 4 patients in the TLHLND group
with complications: 1 ureteral injury, 1 trocar-site hernia, 1 vaginal
laceration, and 1 pelvic abscess. CONCLUSIONS: Node dissection added 56 minutes
and entailed no additional blood loss, transfusion, or length of hospital stay,
as well as minimal risk of complication. Total laparoscopic hysterectomy with
indicated lymph node dissections for endometrial disease is reasonably well
tolerated and warrants prospective randomized study to document its role in the
therapy of endometrial carcinoma.
-----
J Clin Oncol. 2007 Jul 10;25(20):2975-82.
Impact of the human papilloma vaccine on cervical cancer.
Chan JK, Berek JS.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology,
Stanford University School of Medicine, Stanford Cancer Center, Stanford, CA
94305, USA.
During the last decade, research progress on cervical cancer has elucidated the
role of human papilloma virus (HPV) in the pathogenesis of cervical cancer.
Clinical trials on the viral-like particle HPV vaccines have good safety
profiles and promising efficacy in preventing genital warts, cervical neoplasia,
and cervical cancer. The implementation of the HPV vaccine is a tremendous
milestone in our effort toward preventing cervical cancers. However, screening
programs will continue to serve as a critical component in prevention due to the
limitations of the current vaccines. The greatest impact in cervical cancer
incidence worldwide requires improved health care access to underserved areas.
Advances are needed to develop single-dose, heat-stable, needle-free, and
affordable formulations of the HPV vaccine to overcome the socioeconomic
barriers associated with this disease.
-----
J Clin Oncol. 2007 Jul 10;25(20):2966-74.
Management of metastatic cervical cancer: review of the
literature.
Long HJ 3rd.
Department of Oncology, Mayo Clinic College of Medicine, Rochester, MN, USA.
long.harry@mayo.edu
This article reviews the English-language literature concerning chemotherapy for
advanced, recurrent, or metastatic cervix carcinoma. Specifically, it reviews
the available literature for active single agents, doublets, triplets, and
multiple drug combination chemotherapy. Until recently, single-agent cisplatin
was the drug of choice in metastatic cervix cancer. Various doublets, triplets,
and quartlets have been reported to have higher objective response rates than
single-agent cisplatin when compared in phase III clinical trials. Some have
demonstrated improvements in progression-free survival, but only topotecan plus
cisplatin has demonstrated an improvement in overall survival. This benefit is
most apparent in patients who have a long disease-free interval from primary
therapy and who have not received prior cisplatin as a radiosensitizer.
-----
J Clin Oncol. 2007 Jul 10;25(20):2952-65.
Multimodality therapy for locally advanced cervical carcinoma:
state of the art and future directions.
Monk BJ, Tewari KS, Koh WJ.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Chao
Family Comprehensive Cancer Center, University of California-Irvine Medical
Center, Orange, CA 92868, USA. bjmonk@uci.edu
Globally, cervical cancer is the second most common cause of cancer-related
mortality among women causing approximately 234,000 deaths annually among
developing countries and killing 40,000 in developed nations. Most of these
deaths occur in women with bulky or locally advanced cervical cancer,
International Federation of Gynecology and Obstetrics (FIGO) stages IIB through
IVA, when lesions are not amenable to high cure rates with surgery or radiation
(RT). The standard prescription for RT used to treat locally advanced cervical
cancer has been dictated by common practice and patterns of care studies. In
contrast, the addition of concomitant chemotherapy to RT has been studied in a
number of randomized prospective trials, which are discussed in detail. When
added to RT, cisplatin reduces the relative risk of death from cervical
carcinoma by approximately 50% by decreasing local/pelvic failure and distant
metastases. In 1999, weekly intravenous cisplatin at 40 mg/m2 for 6 week
s in combination with RT was established as a new standard for the treatment of
locally advanced cervical carcinoma. More recently, this recommendation has been
expanded to include women with FIGO stage IB2 lesions as well as those with
bulky stage IIA cancers. This monograph reviews the state of the art in treating
locally advanced cervical cancer with combined chemotherapy and RT and discusses
clinical and pathologic prognostic factors that impact cure. Quality of life
during and after multimodality therapy is considered as well as ongoing clinical
trials and future directions.
-----
Expert Opin Pharmacother. 2007 Apr;8(6):809-16.
Uterine papillary serous carcinoma: a review.
Gehrig PA.
University of North Carolina at Chapel Hill, Department of Obstetrics and
Gynecology, CB 7570 MacNider Building, Chapel Hill, NC 27599-7570, USA. pam68@med.unc.edu
The purpose of this article is to review the available literature for uterine
papillary serous carcinoma (UPSC). A literature search was conducted to identify
publications on UPSC. The literature on UPSC is composed mainly of
retrospective, single-institution reports. Despite these limitations, several
recommendations can be made. When UPSC is confirmed on preoperative biopsy,
complete surgical staging should be performed. Although whole abdominal
radiotherapy has a limited role in early-stage UPSC, there may be a role for
postoperative chemotherapy in early-stage UPSC. In the setting of optimally
debulked advanced-stage disease, a combination of radiation and chemotherapy may
be indicated. In the setting of recurrent or suboptimally debulked advanced
disease, a platinum-based regimen is recommended. Although comprising a minority
of the women with endometrial cancer, women with UPSC do account for a
disproportionate percentage of the recurrences. There is a need for clinical
trials to determine the optimal therapy for this cohort of patients.
-----
J Low Genit Tract Dis. 2007 Apr;11(2):90-7.
Outcomes after treatment of cervical intraepithelial neoplasia
among women with HIV.
Massad LS, Fazzari MJ, Anastos K, Klein RS, Minkoff H, Jamieson DJ, Duerr A,
Celentano D, Gange S, Cu-Uvin S, Young M, Watts DH, Levine AM, Schuman P, Harris
TG, Strickler HD.
Department of Obstetrics and Gynecology, Southern Illinois University School of
Medicine, Springfield, IL 62794-9640, USA. lsmassad@ameritech.net
OBJECTIVE: To describe outcomes after treatment of cervical intraepithelial
neoplasia (CIN) in women with HIV. MATERIALS AND METHODS: Women in two
prospective cohort studies, the Women's Interagency HIV Study (WIHS) and the HIV
Epidemiology Research Study (HERS), were followed every 6 months after treatment
of CIN using human papillomavirus (HPV) testing and cytology with colposcopy as
indicated. Identification of CIN or a squamous intraepithelial lesion (SIL)
within 6 months was defined as treatment failure and later disease as
recurrence. RESULTS: Follow-up was available for 170 HIV-seropositive and 15
HIV-seronegative women. Treatment failed in 84 (45%) women (79 HIV seropositive
and 5 HIV seronegative). Failure was more likely in women with lower CD4 counts
(CD4 < 200 cells/microL: odds ratio [OR] = 2.96; 95% CI = 1.4-6.2) and
detectable HPV DNA (OR 8.20; 95% CI = 1.8-37.4; p = .01). After successful
treatment, recurrence-free probabilities at 1,2, 3, and 5 years were .79, .64,
.49, and .34, respectively. HIV-seronegative women were less likely to recur
than HIV-seropositive women (p = .03). In multivariable analysis of HIV-positive
women, recurrence was more likely among women treated for CIN 2,3 (hazard ratio
[HR] = 2.4; 95% CI = 1.4-4.8), those with CD4 count of less than 200 cells/microL
(HR = 2.9; 95% CI = 1.3-6.5) and those with HPV after treatment (HR 2.9; 95% CI
= 1.4-6.1); oncogenic HPV was more strongly associated with recurrence than
nononcogenic HPV (p(trend) = .009). Most failures and recurrences were low
grade, but one adenocarcinoma was diagnosed 4.2 years after therapy for CIN 1.
CONCLUSION: Treatment failure and recurrence are common in women with HIV but
are usually low grade.
-----
Nat Clin Pract Oncol. 2007 Apr;4(4):224-35.
Advances in primary and secondary interventions for cervical
cancer: human papillomavirus prophylactic vaccines and testing.
Wheeler CM.
Department of Molecular Genetics and Microbiology, University of New Mexico
Health Sciences Center, House of Prevention Epidemiology, Building 191, 1816
Sigma Chi Road, Albuquerque, NM 87131, USA. cwheeler@salud.unm.edu
Cytologic screening has greatly reduced the incidence of invasive cervical
cancer in many industrialized nations. State-of-the-art cervical cancer
prevention is costly, however, and includes cytologic screening at repeat
intervals, confirmation of abnormalities by colposcopic biopsy, and treatment of
precancerous lesions. In resource-limited settings, accessibility to prevention
programs for cervical cancer is often poor, or such programs are simply
unavailable or inadequately supported. This disease, therefore, remains a
leading form of cancer among women living in low-resource regions, and over
250,000 women worldwide die from cervical cancer each year. Persistent cervical
infection with one of approximately 15 carcinogenic human papillomavirus (HPV)
types causes virtually all invasive cervical cancer and its precursor
abnormalities, which can be detected by cytologic screening. Genital HPV
infections are primarily transmitted via sexual intercourse. One promising
prophylactic HPV vaccine is available and others continue in development as
primary cervical cancer prevention strategies in younger women. As secondary
interventions, HPV tests are simultaneously evolving for use in cervical cancer
screening programs, including routine screening of older women. HPV testing is
more sensitive and reproducible than cytology with colposcopy for the detection
of cervical precancer and cancer. This article presents current advances and
perspectives on HPV vaccines and HPV testing.
-----
Isr Med Assoc J. 2007 Mar;9(3):156-8.
Human papillomavirus vaccine: the beginning of the end for
cervical cancer.
Bornstein J.
Department of Obstetrics and Gynecology, Western Galilee Hospital, Nahariya,
Israel mdjacob@gmail.com
The human papillomavirus family of viruses causes a variety of benign,
premalignant and malignant lesions in men and women. All cervical cancers are
caused by HPV. It is the leading cause of death from cancer in women in
developing countries; every year some 493,000 women develop cervical cancer and
230,000 die every year from this disease. The vaccine against HPV includes
virus-like particles, composed of the major viral capsid protein of HPV without
the carcinogenic genetic core. Large-scale studies have shown that the vaccine
is tolerated well, leads to high antibody levels in both men and women, and
prevents chronic HPV infection and its associated diseases. To achieve effective
coverage the vaccine should be given prior to sexual debut. Introduction of the
vaccine into specific countries, particularly Israel, should take into account
the local incidence of cervical cancer as well as the increasing incidence of
precancerous cervical lesions and genital warts, which reduce quality of life
and are associated with considerable costs.
-----
Int J Gynecol Cancer. 2007 Mar 13; [Epub ahead of print]
Current treatment options in uterine endometrial stromal sarcoma:
report of a case and review of the literature.
Ihnen M, Mahner S, Janicke F, Schwarz J.
Klinik und Poliklinik fur Gynakologie, Universitatsklinikums Hamburg-Eppendorf,
Hamburg, Germany.
Uterine sarcomas are a rare form of uterine cancer. They occur in women from 40
to 60 years and are generally characterized by poor prognosis, a high rate of
local recurrence, and distant metastases. Endometrial stromal sarcoma (ESS)
accounts for 0.2% of all gynecological malignancies. Forms of possible treatment
include surgery, radiotherapy, chemotherapy, and endocrine treatment. Randomized
trials analyzing these treatment options are limited due to the rarity of this
disease; therefore, a standard therapy could not be established thus far. To
present an overview of the current treatment options of ESS, a search of
Medline, Embase, and the Cochrane Library was performed and the results
concluded. We report the case of a 32-year-old woman who presented with FIGO
stage II ESS. Initial treatment with tamoxifen and local perfusion with
cisplatin resulted in disease progression and were discontinued. A novel,
therapeutic approach using two cycles of combination chemotherapy with
doxorubicin and ifosfamide followed by surgery was applied. Five years after
surgery, the patient is still in complete remission. Thus, we conclude that
although there is no data from randomized trials available, chemotherapy in
advanced or metastatic ESS can provide an opportunity for surgical treatment and
can lead to long-term remission.
-----
Obstet Gynecol. 2007 Mar;109(3):655-62.
Prognostic factors for uterine cancer in reproductive-aged women.
Lee NK, Cheung MK, Shin JY, Husain A, Teng NN, Berek JS, Kapp DS, Osann K, Chan
JK.
Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and
Reproductive Sciences, University of California, San Francisco, California
94143, USA.
OBJECTIVE: To determine the prognostic factors that influence the survival of
younger women diagnosed with uterine cancer. METHODS: Demographic and clinico-pathologic
data were collected from the National Cancer Institute database between 1988 and
2001. Data were analyzed with Kaplan-Meier methods and Cox proportional hazards
regression. RESULTS: Of the 51,471 women diagnosed with uterine cancer in the
study period, 2,076 (4.0%) patients were aged 40 years or younger, and 49,395
(96.0%) were older than 40. The mean age in the younger group was 35.6 years,
compared with 65.2 years of the older group. The overall distribution by stage
was stage I 75.4%, II 8.1%, III 6.7%, and IV 9.8%. Younger patients were more
likely to be nonwhite (42.4% versus 18.3%, P<.001) and have stage I disease
(79.2% versus 75.3%, P<.001), grade 1 lesions (47.6% versus 35.6%, P<.001), and
sarcomas (15.9% versus 8.2%, P<.001) compared with their older counterparts. The
overall 5-year disease-specific survival for younger patients was significantly
better than that of older women (93.2% versus 86.4%, P<.001). On multivariable
analysis, younger age, earlier stage, lower grade, nonblack race, endometrioid
histology, and surgical treatment remained as significant independent prognostic
factors for improved survival. CONCLUSION: This large population-based study
demonstrates that patients 40 years and younger have an overall survival
advantage compared with women older than 40 years, independent of other clinico-pathologic
prognosticators. LEVEL OF EVIDENCE: III.
-----
Int J Gynecol Cancer. 2007 Jan-Feb;17(1):215-9.
Early-stage carcinosarcoma of the uterus: the significance of
lymph node count.
Temkin SM, Hellmann M, Lee YC, Abulafia O.
Division of Gynecologic Oncology, SUNY, State University of New York-Downstate,
450 Clarkson Avenue, Brooklyn, NY 11203, USA. sarah.temkin@gmail.com
Carcinosarcoma is a rare tumor of the uterus with a poor prognosis, even when
identified and treated at an early stage. The purpose of this study was to
identify and analyze prognostic pathologic features and treatment outcomes in
patient with stages I and II carcinosarcoma of the uterus. Patients with
carcinosarcoma of the uterus who received primary surgical treatment between
1984 and 2004 were identified through an institutional tumor registry. Inclusion
criteria were clinical stage I/II disease following hysterectomy and selective
pelvic and para-aortic lymph node sampling. Regression analysis was used to
determine risk factors for recurrence and survival. Disease-free and overall
survival were then determined using Kaplan-Meier analysis. Forty-seven patients
with stages I and II carcinosarcoma of the uterus were identified. Age,
heterologous or homologous histology, and type of adjuvant treatment were not
associated with recurrence or survival. Depth of myometrial invasion was found
to correlate to disease-free survival but not overall survival. The number of
lymph nodes collected correlated to risk of recurrence and survival.
Disease-free and overall survival were greater in patients with higher lymph
node count. We conclude that the number of lymph nodes collected was the only
risk factor that was found to be correlated to recurrence and survival in
patients with early-stage carcinosarcoma. These results support mounting
evidence that lymphadenectomy is crucial in patients with carcinomas of the
uterus in order to discover occult metastatic disease and potentially provide
patients with a therapeutic benefit.
-----
Int J Gynecol Cancer. 2007 Jan-Feb;17(1):137-40.
Resection of recurrent cervical cancer after total pelvic
exenteration.
Mourton SM, Sonoda Y, Abu-Rustum NR, Bochner BH, Barakat RR, Chi DS.
Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer
Center, 1275 York Avenue, New York, NY 10021, USA.
The objective of this study was to describe the management of patients with
recurrent cervical cancer after total pelvic exenteration (TPE). We reviewed the
records of patients who underwent TPE for recurrent cervical cancer between June
1992 and December 2003 and subsequently developed recurrent disease.
Thirty-seven patients underwent TPE during the study period, and 25 (68%)
subsequently developed recurrence proven by radiographic and/or biopsy studies.
Recurrence sites included pelvic (12), inguinal (5), retroperitoneal (5),
hepatic (4), vulva (2), perineum (1), transposed ovary (1), and lung (1). The
median time to recurrence was 7 months (range 2-73 months), with 92% (23/25)
occurring within 2 years of TPE. Management of recurrence was known in 21 of 25
patients, which included chemotherapy (10), surgical resection (7), and no
further treatment (4). Surgically resected recurrences were isolated to the
groin (2), vulva (2), perineum (1), transposed ovary (1), and psoas muscle (1).
The four patients who underwent ovarian, perineal, and vulvar resections
succumbed to their disease in a median time of 13 months (range 2-21 months). Of
the two patients with surgically resected groin recurrences, one is alive with
disease 21 months after initial recurrence and the other is alive without
evidence of disease 85 months later. One patient had an isolated 4-cm recurrence
involving the psoas muscle and the femoral nerve and is without the evidence of
disease 9 months later. Resection of isolated recurrences after TPE is a
reasonable option in selected patients, particularly in those with solitary
inguinal metastases.
-----
Cancer Res. 2006 Nov 1;66(21):10229-32.
Prospects for cervical cancer prevention by human papillomavirus
vaccination.
Schiller JT, Lowy DR.
Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer
Institute, Bethesda, Maryland 20892, USA. schillej@dc37a.nci.nih.gov
Recent clinical trials in young women have shown that subunit vaccines based on
human papillomavirus (HPV) 16 and HPV18 L1 virus-like particles are
approximately 100% effective in short-term prevention of persistent cervical
infection and of cervical dysplasia by these major oncogenic types. These
remarkable efficacy results, together with an excellent safety profile in
thousands of vaccinated women, have led to the HPV prophylactic vaccine from one
manufacturer having now been licensed for commercial use and the expectation
that the vaccine from a second manufacturer will be approved in the near future.
These vaccines seem to have great potential for reducing cervical cancer deaths
and treatments to remove premalignant cervical lesions. However, before their
public health effect can be fully estimated, several issues must be addressed.
These include duration of protection, degree of cross-protection against
nonvaccine types, efficacy in men, and vaccine availability to economically
disadvantaged women.
-----
Expert Opin Biol Ther. 2006 Nov;6(11):1223-7.
HPV vaccination with Gardasil: a breakthrough in women's health.
Hanna E, Bachmann G.
Women's Health Institute, UMDNJ-Robert Wood Johnson Medical School, 125 Paterson
Street, Cab 2104, New Brunswick, New Jersey 08901, USA.
Human papillomavirus (HPV) represents one of the most common sexually
transmitted infections. Although infection is often self-limited, a percentage
of women with HPV infection will go on to develop cervical precancerous or
cancerous lesions. It is estimated that HPV16 is responsible for approximately
half of all cervical cancers worldwide. Several studies have tested vaccines
directed against specific HPV types, namely types 6, 11, 16 and 18. This paper
reviews these studies, particularly focusing on a quadrivalent (type 6, 11, 16
and 18) HPV L1 virus-like particle vaccine under investigation in Phase III
trials at present. Data indicate that this vaccine, referred to as Gardasil, can
prevent precancerous cervical lesions and early in situ cervical cancers with
few adverse effects, and the vaccine has been approved by the FDA for this
indication. Another vaccine, HPV16 L1, directed solely against HPV16, has also
been demonstrated to be effective (at present, follow-up has been for up to 48
months) in providing protection against persistent infection with this viral
strain and preventing HPV16-related cervical intraepithelial neoplasia 2/3,
while producing minimal adverse effects in recipients. Given the lack of a
pharmacological intervention that can eradicate HPV in infected individuals and
the prevalence of cervical cancer secondary to HPV infection across the world,
the HPV vaccine represents a significant breakthrough in women's health.
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Oncology (Williston Park). 2006 Oct;20(11):1401-4, 1410; discussion 1410-11,
1415-6.
Topotecan in combination with cisplatin for the treatment of
stage IVB, recurrent, or persistent cervical cancer.
Brave M, Dagher R, Farrell A, Abraham S, Ramchandani R, Gobburu J, Booth B,
Jiang X, Sridhara R, Justice R, Pazdur R.
Office of Oncology Drug Products, Center for Drug Evaluation and Research, US
Food and Drug Administration, Silver Spring, Maryland 20993, USA. michael.brave@fda.hhs.gov
PURPOSE: Topotecan, a camptothecin analog previously approved for the treatment
of ovarian cancer and small-cell lung cancer, was granted regular approval by
the US Food and Drug Administration (FDA) on June 14, 2006, for use in
combination with cisplatin to treat women with stage IVB, recurrent, or
persistent carcinoma of the cervix not amenable to curative treatment with
surgery and/or radiation therapy. The purpose of this summary is to review the
database supporting this approval. EXPERIMENTAL DESIGN: In a randomized
multicenter study enrolling 293 eligible patients, topotecan plus cisplatin (TC)
was compared with cisplatin monotherapy. The TC regimen consisted of cisplatin
50 mg/m2 IV over 1 hour on day 1 and topotecan 0.75 mg/m2 IV over 30 minutes on
days 1, 2, and 3 every 21 days. RESULTS: There was a clinically relevant and
statistically significant improvement in overall survival in the TC treatment
arm. Median overall survival was 9.4 months (95% confidence interval
[CI]:7.9-11.9) in the TC arm, compared to 6.5 months (95% CI:5.8-8.8) with
cisplatin alone. The unadjusted hazard ratio for overall survival between
treatment arms was 0.76 (95% CI: 0.59-0.98, P = .033) favoring the combination
arm. The most common toxicities with TC included myelosuppression, nausea and
vomiting, mucositis, rash, and hepatotoxicity. CONCLUSIONS: This report
describes the FDA's review supporting this first approval of a chemotherapeutic
drug for advanced cervical cancer based on demonstration of a survival benefit.
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Cleve Clin J Med. 2006 Oct;73(10):929-35.
Using the new HPV vaccines in clinical practice.
Widdice LE, Kahn JA.
Division of Adolescent Medicine, Cincinnati Children's Hospital Medical Center,
University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
lea.widdice@cchmc.org
Gardasil, a vaccine against human papillomavirus (HPV), recently became
available in the United States for use in girls and women 9 to 26 years of age.
A second HPV vaccine, Cervarix, is under development. These vaccines constitute
the most significant development in cervical cancer prevention in the last 60
years, having the potential to reduce the incidence of cervical cancer by up to
70%
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Int J Gynecol Cancer. 2006 Sep-Oct;16(5):1927-32.
Laparoscopically assisted radical vaginal hysterectomy (Coelio-Schauta):
A comparison with open Wertheim/Meigs hysterectomy.
Sharma R, Bailey J, Anderson R, Murdoch J.
Department of Gynaecology, St. Michaels Hospital, United Bristol Healthcare
Trust, Bristol, England.
The objective of this study was to compare the safety, efficacy, and short-term
benefits of the Coelio-Schauta procedure with open Wertheim/Meigs radical
abdominal hysterectomy. We retrospectively analyzed records of our first 35
consecutive patients undergoing laparoscopically assisted radical vaginal
hysterectomy (LARVH) for early cervical cancer and 32 consecutive patients of
open radical hysterectomy (ORH) performed between 1999 and 2005 in our
institution. We analyzed patient age, bodyweight, previous abdominal surgery,
operating time, blood loss, perioperative complications, postoperative bladder
dysfunction, other postoperative complications, and histologic type. The FIGO
stage, excision margins, node count and node status, follow-up, and recurrence
rates were also taken into account. We excluded stage IA and stage II disease
patients to reduce the impact of tumor size on the outcome of the surgery. This
left 27 patients with stage IIB disease who had LARVH and 28 patients with stage
IB disease who had ORH. These patients formed the study group. The cohorts were
similar in age, bodyweight, previous abdominal surgery, histologic subtype, FIGO
stage, resection margins, node count and node status, length of follow-up, and
recurrence. There were statistically significant differences between LARVH and
ORH for duration of surgery (mean 160 vs 132 min), intraoperative blood loss
(479 vs 715 mL), hospital stay (mean 5 vs 9.3 days), postoperative complications
(6 vs 20 patients), and duration of bladder catheterization (mean 4.4 vs 8.8
days). Four LARVH patients and no ORH patients had urinary tract injury that was
repaired. None had long-term sequelae. Our data confirm that LARVH is a suitable
alternative to ORH hysterectomy for small-volume stage IB1 cervical cancer with
similar clinical efficacy and a superior postoperative recovery and
postoperative morbidity profile. Urinary tract trauma is a clear risk in the
early stages of the learning curve.
-----
Int J Gynecol Cancer. 2006 Sep-Oct;16(5):1855-61.
Erythropoietin administration during primary treatment for
locally advanced cervical carcinoma is associated with poor response to
radiation.
Temkin SM, Hellmann M, Serur E, Lee YC, Abulafia O.
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, SUNY
Downstate Medical Center, Brooklyn, New York 11203, USA. sarah.temkin@gmail.com
The purpose of this study was to determine whether the use of recombinant
erythropoietin (r-EPO) during treatment for locally invasive carcinoma of the
cervix affects recurrence rates, disease-free survival, and overall survival.
Retrospective analysis of outcomes of patients with locally advanced cervical
cancer treated with radiation and concurrent chemotherapy between January 1997
and July 2004 was performed. Recurrence rates, disease-free survival, and
overall survival were calculated using SPSS statistical software. Throughout P <
0.05 was considered significant. Of 68 patients included in this study, 18
patients received erythropoietin during treatment and 50 did not. Patient age,
stage, hemoglobin at presentation, and average weekly hemoglobin (AWH) were
similar in both groups of patients. The recurrence rate among patients who
received r-EPO was 61% compared with 30% among patients who did not receive r-EPO
(P = 0.014). Eight of 18 patients (44%) who received r-EPO were alive at last
known follow-up compared to 36 of 50 (72%) who did not receive the medication (P
= 0.045). Disease-free survival and overall survival were significantly shorter
in patients who received r-EPO during treatment (P = 0.028, 0.032). The
administration of r-EPO during primary treatment of patients with locally
advanced cervical cancer is associated with increased recurrence rate, increased
risk of death due to disease, and decreased disease-free and overall survivals.
-----
Int J Gynecol Cancer. 2006 Sep-Oct;16(5):1839-45.
Pattern of failure and long-term morbidity in patients undergoing
postoperative radiotherapy for cervical cancer.
Jain P, Hunter RD, Livsey JE, Coyle C, Kitchener HC, Swindell R, Davidson SE.
Department of Clinical Oncology, Christie Hospital, Manchester, United Kingdom.
pooja.jain@christie-tr.nwest.nhs.uk
The objective of this study was to assess treatment outcomes in a large case
series of cervical cancer patients undergoing postoperative radiotherapy in a
single center. Case notes of women referred to the Christie Hospital during
1985-1997 for postoperative adjuvant radiotherapy for cervical cancer were
reviewed. Of 478 women eligible for analysis, 282 (58.9%) underwent radical
hysterectomy and 196 (41.1%) had nonradical hysterectomy. The disease-specific
5-year survival for the study population is 70.1%, with a 5-year risk of
developing any recurrence of 30.5% and a 5-year grade 3 morbidity rate of 3.9%.
Survival was significantly higher, ie, 80.9% vs 62.7% (P = 0.0001) and
recurrence was significantly lower, ie, 18.6% vs 38.8% (P < 0.00005) in the
group of women who had adjuvant radiotherapy following a nonradical hysterectomy
compared with radical surgery. Thirty percent of women having "radical" surgery
had positive resection margins and required postoperative adjuvant pelvic
radiotherapy. Women with node-positive disease, who received adjuvant
radiotherapy, had a high rate of distant metastases. These women would receive
chemoradiotherapy now as primary treatment because of the risk of developing
distant metastases. If, despite staging investigations, surgery reveals
node-positive disease, then these women should receive adjuvant
chemoradiotherapy. Survival was better in women who had nonradical surgery due
to smaller volume disease when cancers were unsuspected and hence will have been
cured by surgery alone. Multidisciplinary team working, as recommended by
national guidelines from 1999, should allow better patient selection for
treatment.
Previous Uterine Cancer
Research: 2002-2006
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