Application an internet facilitation in a community-based cervical cancer screening project.

OBJECTIVE: To evaluate the feasibility of an internet-facilitated community model for cervical cancer screening using self-collected HPV testing as primary screening. METHOD: A population-based cervical cancer screening program was conducted in the suburb of Shenzhen, China, from September 2014 to July 2017. Women with 25-60 years of age and no pregnancy were eligible for participation. Participants could register for screening by logging in a website by themselves or with the aids of local community workers. A unique barcode was issued to each applicant upon successful registration. After registration, women could get sampling kits from community screening site/study clinic, collect vaginal samples privately or in group, and provide their sample for Hr-HPV tests on Cobas4800 and SeqHPV assays. Testing reports were checkable through personal account for all participant and phone calls were given to all women positive of Hr-HPV. Participants positive of both or either the 2 assays were identified as the positives. The positives could return the study clinic for triage or search medical care in other clinics. Colposcopy directed or ramdom biopsies were performed on all positives who returned to the study clinics. RESULTS: A total of 10,792 community women registered for screening, among whom, 10,010 provided their vaginal samples for tests. 99.5% of the participants were confirmed to have correct personal identifiable information and samples, and 98.9% of them got HPV testing results from both or either assays. No adverse event was reported. CONCLUSION: When self-collected HPV testing is used as the primary testing, the internet-based data platform facilitates the screening in registration, data collection, and data tracking, and increases the screening coverage. Internet-facilitated community model is promising to cervical cancer control and applicable in regions with variety of resources.

Comparison of cycle threshold values of the Cobas HPV test and viral loads of the BMRT HPV test in cervical cancer screening.

Objective: To validate the HPV viral loads that are reflected by the cycle threshold values of Cobas4800 as the viral load indicators by verifying the consistency of the viral loads per unit (10,000 cells) from the BMRT assay. Methods: The analysis is based on data from the Chinese Multi-Center Screening Trial (CHIMUST). The cases included in the analysis are all positive for physician-collected hrHPV on SeqHPV and/or Cobas4800 or negative for hrHPV but abnormal in cytology (≥LSIL), and some cases selected by nested case-control randomization from those negative for physician-collected hrHPV and cytology. With HPV testing results and relevant Ct values from Cobas4800 available, we tested the entire sample set with the BMRT HPV testing assay and analyzed their agreement with Cobas4800, followed by a comparison of the CtV from Cobas4800 and viral loads (lg) from BMRT by lesion grade. Results: We included 4,485 women (mean age: 45.4 years) in the study, and 4,290 had complete data. The consistency of genotypes from Cobas4800 and BMRT for hrHPV, HPV-16, HPV-18, and 12-HPV pools was 94.9% (4070/4290, Kappa = 0.827), 99.1% (4251/4290, Kappa = 0.842), 99.6% (4,273/4,290, Kappa = 0.777), and 95.3% (4,089/4,290, Kappa = 0.821), respectively. Further analysis shows that any inconsistency between the two assays is likely among samples with comparatively lower viral loads. When analyzing per lesions of CIN2+ and CIN3+, the CtV from Cobas4800 and VL (lg) from BMRT are highly correlated inversely and follow the linear regression for HPV16 and 12-HPV pool (Pearson's or Spearman's correlation coefficient (r): In CIN3+, r HPV16 = -0.641, P < 0.001; r 12-HPVpool = -0.343, P = 0.109; In CIN2+, r HPV16 = -0.754, P < 0.001; r 12-HPVpool = -0.429, P < 0.001). Conclusion: The CtV from Cobas4800 and the viral loads (lg) of per unit cells from the BMRT are well correlated for lesion grading when tested on physician-collected samples. Cobas-CtV is worthy of further study for clinical application.

Prevalence of Human Papillomavirus Among Chinese Han and Mongols Minority Women in Inner Mongolia, China: Reflected by Self-Collected Samples in CHIMUST.

Background: The disparities of hr-HPV infection among races/ethnicities have not been fully discussed. This study aimed to investigate the difference of hr-HPV infection between Chinese Han and Mongols minority women in Inner Mongolia. Methods: Genotyping and histopathology data of Chinese Han and Mongols minority women in Inner Mongolia from Chinese Multi-Center Screening Trial were used to analyze the hr-HPV prevalence, and type-specific distribution in abnormal pathology results. Results: The hr-HPV infection rates of Han women was 15.9% while of Mongols was 21.6% (P < 0.001). The most prevalent genotypes in Han women were ranked as HPV-16,-52,-18/-58,-31/-39, and-59 while in Mongols were-16,-31,-58,-18 and-52. When analyzing the age-specific of hr-HPV infection, two peaks were found at age of 40-44 (20.5%) and 55-59 (23.5%) years in Han women while three peaks were observed at age of 30-34 (22.1%), 45-49 (22.9%), and 55-59 (31.8%) years, respectively, in Mongols. HPV-16 accounting for 62.5 and 53.8% of the CINII+ in Han and Mongols, respectively. Conclusion: The prevalence of hr-HPV was significantly different between the Han and Mongols minority women in Inner Mongolia, races/ethnicities background should be taken into consideration for the refinement of cervical cancer screening strategies and vaccine implementation in China.

[Performance of vaginal self-sampling high-risk HPV genotyping as primary and combining cytology or viral load as secondary in cervical cancer screening].

Objective: To evaluate the efficacy of high-risk HPV (HR-HPV) genotyping with vaginal self-sampling in primary screening and combining cytology or viral load for HR-HPV positive as secondary screening strategies. Methods: The data referring to HR-HPV genotyping of self-collected sample with mass array matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS), HR-HPV viral load of physician-collected sample with hybrid capture Ⅱ (HC-Ⅱ), liquid-based cytology and histology of 8 556 women were from Shenzhen cervical cancer screening trial Ⅱ (SHENCCAST-Ⅱ) conducted between April 2009 and April 2010. The data were reanalyzed to determine the sensitivity and specificity to cervical intraepithelial neoplasia (CIN) of grade 2 or worse (CIN Ⅱ+), CIN of grade 3 or worse (CIN Ⅲ+) when HR-HPV genotyping combining with colposcopy as primary screening strategy based on varied HR-HPV subtype (strategy 1, including 5 sub-strategies: 1a: HPV 16/18 positive; 1b: HPV 16/18/58 positive; 1c: HPV 16/18/58/31/33 positive; 1d: HPV 16/18/58/31/33/52 positive; 1e: any HR-HPV positive). The data were also compared to determine the efficacy of cytology (strategy 2, including 5 sub-strategies: 2a, 2b, 2c, 2d, 2e) or HR-HPV viral load (strategy 3, including 4 sub-strategies: 3a, 3b, 3c, 3d) of physician-collected sample as a triage with HR-HPV genotyping for self-sampling HR-HPV positives. Results: (1) The HR-HPV positive rate was 13.77% (1 178/8 556) in the self-collected samples of 8 556 pregnant women. Of them,the prevalences of HPV 16/18, HPV 16/18/58, HPV 16/18/58/31/33 and HPV 16/18/58/31/33/52 were 3.16% (270/8 556), 5.14% (440/8 556), 6.66% (570/8 556) and 9.81% (839/8 556), respectively. The HR-HPV viral load ≥10 relative light units/control (RLU/CO) was 8.87%(759/ 8 556), while cytological results ≥atypical squamous cell of undetermined signification (ASCUS) were 12.05% (1 031/8 556). (2) The strategy 1e had the highest sensitivities for CIN Ⅱ+, CIN Ⅲ+ which were 92.70% and 94.33%,respectively,among 14 sub-strategies,while the lowest specificity and positive predictive value (PPV). Meanwhile,the required colposcopy referral rates were much higher than other 13 sub-strategies (13.77%). The other 4 sub-strategies of strategy 1 (1a, 1b, 1c, 1d), strategy 1a had the highest specificities for CIN Ⅱ+ and CIN Ⅲ+ (97.92%, 97.69%, respectively), while 1d had the highest sensitivities for CIN Ⅱ+ and CIN Ⅲ+ (88.41%, 92.20%, respectively). (3) Both strategies of referring self-sampling HPV 16/18 positives for immediate colposcopy followed by triage physician-collected sample cytology (≥ASCUS) or viral load (≥10 RLU/CO) for non-HPV 16/18 positives had significantly higher sensitivity and specificity for CIN Ⅱ, CIN Ⅲ+, as well as lower referral rates (strategy 2a and 3a). Additionally, based on these two secondary screening strategies, cumulatively using the other four HR-HPV (HPV 58, 31, 33 and 52) positives as triage for immediate colposcopy showed an enhanced sensitivity. Conclusions: Primary HR-HPV cervical cancer screening strategy based on self-sampling with triage of cytology (≥ASCUS) or viral load (≥10 RUL/CO) provides a good balance among sensitivity, specificity for CIN Ⅱ+ and CIN Ⅲ+ and the number of tests required, referral rates. The efficacy of HR-HPV genotyping combining cytology or viral load secondary screening strategies will have a spiral escalation when HPV 58, 31, 33, 52 are included.

Evaluation of an isothermal amplification HPV detection assay for primary cervical cancer screening.

OBJECTIVE: The aim of this research was to evaluate independently the performance of a new isothermal amplification assay for cervical cancer screening compared to two previously validated PCR-based assays and histologic endpoints. METHODS: This is a sub-study from the Chinese multi-center screening trial (CHIMUST). The self-collected and clinician-collected specimens stored in PreservCyt at - 4 °C from 6042 women with complete data were tested with the AmpFire assay. These specimens had been previously tested with Cobas and SeqHPV assays. In the primary study all patients with an abnormal test were referred to colposcopy where all had directed and/or random biopsies plus ECC. No additional patients were called back based on the AmpFire results. RESULTS: 6042/6619 women had complete data (mean age 44.1). There were 57 cases of CIN 2, 35 cases of CIN 3 and 2 cancers. The sensitivity for CIN2+ and CIN3+ were similar among the three assays (both direct and self-collected). For the specificities in all categories (CIN2+/CIN3+ and self and direct collection), isothermal amplification assay was either equal to or more specific than Cobas but consistently less specific than SeqHPV. CONCLUSION: The AmpFire HPV assay showed similar sensitivity to Cobas and SeqHPV for CIN2+ and CIN3+ on both self and clinician-collections (P>0.05), with good specificity. The speed, low cost, and simplicity of this assay will make it particularly suited for low and middle resource settings. Its accuracy with self-collection makes it applicable for mass screening programs.

Colposcopy.

Though in the 1980s, colposcopically-directed biopsy excluded over 90% of CIN 3 and cancer (CIN 3+), recent reviews found sensitivity of colposcopically-directed biopsy for CIN 3+ of 50-65%. Studies from China showed that the sensitivity of colposcopically-directed biopsy for CIN 3+ is higher for large CIN 3+ than for small CIN 3+ and higher for associated high-grade cervical cytology than for low-grade cervical cytology. Colposcopically-directed biopsy excluded over 90% of CIN 3+ in the 1980s because colposcopy clinics in the 1980s evaluated women with high-grade cytology that had large CIN 3+; it no longer excludes CIN 3+ well because current colposcopy clinics evaluate women with low-grade cytology that have small CIN 3+. When colposcopically-directed biopsy is used to exclude CIN 3+ our understanding of the natural history of CIN is skewed, errors occur in defining appropriate screening practice, and inaccurate diagnosis results in incorrect treatment. The impression that CIN is more common on the anterior lip of the cervix is an artifact introduced by the inaccuracy of colposcopy. An unjustified enthusiasm for screening with acetic acid aided visual inspection (VIA) occurred when the sensitivity of VIA for CIN 3+ was inflated by screening studies using colposcopically-directed biopsy as the gold-standard for CIN 3+. To limit the harm of inaccurate diagnosis associated with colposcopically-directed biopsy, at colposcopy we advise random biopsies at the squamocolumnar junction in cervical quadrants without visible lesions and, unless the woman is pregnant, endocervical curettage (ECC). As the diagnosis of CIN 3+ solely by ECC is uncommon in women under age 25, the ECC may be omitted in women under age 25 years. If multiple cervical biopsies are performed, to limit discomfort, a bronchoscopy biopsy instrument which obtains 2-mm biopsies should be used.

Total laparoscopic hysterectomy versus laparoscopic-assisted vaginal hysterectomy in endometrial cancer: surgical and survival outcomes.

STUDY OBJECTIVE: To compare surgical and survival outcomes of patients with early-stage endometrial cancer (EC) who underwent total laparoscopic hysterectomy (TLH) or laparoscopic-assisted vaginal hysterectomy (LAVH) +/- lymphadenectomy. DESIGN: Retrospective, nonrandomized clinical study (Canadian Task Force classification II-2). SETTING: Two tertiary care academic medical centers. PATIENTS: Patients with EC treated by TLH or LAVH from 1998 through 2006. INTERVENTIONS: TLH and LAVH were performed in 80 and 24 patients, respectively. Patient demographics and clinical variables were collected, and surgical and survival outcomes were determined. MEASUREMENTS AND MAIN RESULTS: Median operating time was significantly higher for patients undergoing LAVH than for those undergoing TLH (212.5 and 183.5 minutes, respectively; p = .039). EBL was also greater in patients undergoing LAVH (median 220 mL) compared with those undergoing TLH (median100 mL; p = .001). After a median follow-up time of 51.5 months, there was no difference in recurrence or survival rates between the groups. CONCLUSION: Early-stage EC can be treated effectively with either TLH or LAVH. TLH patients may experience shorter operating times and less blood loss. When performed by experienced laparoscopists, TLH may be more feasible than LAVH in this cohort of patients.

Optical coherence tomography as a diagnostic aid to visual inspection and colposcopy for preinvasive and invasive cancer of the uterine cervix.

The purpose of this study was to determine the sensitivity and specificity of optical coherence tomography (OCT) under two well-defined clinical settings. First, as an aid to cervical cancer screening, using visual inspection with acetic acid (VIA) in low-resource settings, and the second, as an adjunct to the traditional management of abnormal cervical cytology with colposcopy and biopsy. Patients referred for colposcopy with > or = atypical squamous cells of undetermined significance were accrued for the study. Each subject underwent VIA and colposcopy. OCT was performed in all VIA- and colposcopy-positive areas and at the squamocolumnar junction in all four quadrants. The sensitivity of VIA for > or = cervical intraepithelial neoplasia 2 was 76% (95% CI 58-88). When OCT was applied to VIA as a secondary screen, the specificity improved from 34% (95% CI 27-41) to 61% (95% CI 60-74). With liberal diagnostic criteria for the majority of the colposcopy examinations, OCT showed an even greater relative improvement in specificity. OCT proved to be a fair diagnostic modality (receiver operating characteristic curve 0.73) adjunctive to VIA and colposcopy. On the basis of the above findings, we believe that this technology could potentially show greatest utility in the management of cervical dysplasia in low-resource settings where a single episode of care is most desirable.

Diagnostic efficacy of optical coherence tomography in the management of preinvasive and invasive cancer of uterine cervix and vulva.

The purpose of this study was to understand the capabilities and utility of optical coherence tomography (OCT) in characterizing tissue in patients with precancer and cancer of the uterine cervix and vulva. OCT is an optical technique that uses low-coherence interferometer to develop a two-dimensional image of optical scattering from internal tissue microstructure. This study was designed to develop diagnostic criteria. Women undergoing colposcopic evaluation secondary to an abnormal Papanicolaou smear or visualized grossly abnormal vulvar lesion comprised the study population. Under colposcopic visualization, the OCT device was applied to normal regions in all patients and abnormal areas when present, and images were captured. Each subject then underwent multiple directed biopsies. Images were then reviewed and compared with matched histology. A total of 50 women were recruited for the study. Of the 50 patients evaluated, 18 had cervical intraepithelial neoplasia (CIN) II,III, 14 had CIN I, 13 had metaplasia/inflammation, two had invasive squamous cell carcinoma of the cervix, and three had a diagnosis of Paget's disease of the vulva. Analysis of the OCT images showed a repetitive pattern that represented normal squamous epithelium of the cervix in 100% of the normal biopsies. Images of the 18 patients with histologically proven CIN II,III showed an unstructured homogeneous highly backscattering region with fast attenuation of the signal in 16 (89%) of the patients. OCT is a new approach for the early identification of cervix and vulvar malignancies. Using information inherent to the returning photon signals from tissue, early morphological and light-scattering changes can be detected during tumorigenesis. It has the potential to be a true optical biopsy. If diagnostically comparable to a biopsy, then clearly the ability of OCT to provide a point of service diagnosis would serve a significant advantage.

Shanxi Province cervical cancer screening study II: self-sampling for high-risk human papillomavirus compared to direct sampling for human papillomavirus and liquid based cervical cytology.

The objective of this study was to compare the sensitivity and specificity of a new method for self-sampling for high risk human papillomavirus (HPV) with direct sampling and liquid based cervical cytology. In Shanxi Province, China, 8,497 women (ages 27-56) underwent a self-sample for HPV using a conical-shaped brush placed into the upper vagina and rotated. Three to sixteen months later the women were screened with liquid-based cytology and direct HPV tests. Subjects with any abnormal test underwent colposcopy and multiple biopsies. Mean age was 40.9 years. 4.4 percent of subjects had >or=CIN II, 26% a positive self-sample and 24% a positive direct test for HPV. The sensitivity for detection of >or=CIN II was 87.5% for self-sampling, and 96.8% for the direct test (P < 0.001). The specificity was 77.2% for the self-sample and 79.7% for the direct test. With an abnormal Pap defined as ASCUS or greater the sensitivity of the Pap for the detection of >CIN II was 88.3% and the specificity was 81.2%. We conclude that self-sampling for HPV is less sensitive for >CIN II than the direct test, but similar to liquid based cytology.

The effect of radiation therapy on brain metastases from endometrial carcinoma: a retrospective study.

OBJECTIVE: The objective of this study was to investigate the effectiveness of radiation therapy as a treatment for brain metastases from endometrial carcinoma. METHODS: Between July 1985 and November 1999, 10 patients with brain metastases from endometrial carcinoma were treated at the Cleveland Clinic. We reviewed the patient and tumor characteristics at the time of the primary diagnosis and the brain metastases diagnosis. For the 8 patients who received radiation therapy with or without surgery, we analyzed the treatment results with regard to survival and local control of the metastases. RESULTS: Brain metastases from endometrial carcinoma were commonly accompanied by uncontrolled local-regional disease and systemic metastases. Multiple brain lesions developed in 7 of 10 patients. Two patients were treated with surgery alone and had a median survival of 2.75 months (4 and 1.5 months) after the brain metastases diagnosis. Three patients were treated with surgery and radiation therapy and lived for a median survival of 15 months (range 11.5 to 15.5 months). The 5 patients who were treated with radiation therapy without surgery had a median survival of 2.4 months (range 0.25 to 6 months). Patients with multiple brain metastases had a shorter survival than patients with a single metastasis. CONCLUSION: Overall survival after brain metastases development in patients with endometrial carcinoma was poor. Although the number of patients was small, radiation therapy alone resulted in poor survival. Combination treatment with surgery and radiation therapy may improve survival for selected patients.

The colposcopic impression. Is it influenced by the colposcopist's knowledge of the findings on the referral Papanicolaou smear?

OBJECTIVE: To determine whether the colposcopic impression is influenced by the colposcopist's knowledge of the referral Papanicolaou smear. STUDY DESIGN: Using a community hospital database, the accuracy of the colposcopic impression (accuracy = proportion of women with histology greater than cervical intraepithelial neoplasia [CIN] 2 that have colposcopic impressions of greater than CIN 2) when referral smears were atypical squamous cells of uncertain significance (ASCUS), atypical glandular cells of uncertain significance (AGUS) or low grade squamous intraepithelial lesion (LSIL) was compared to that when smears showed high grade squamous intraepithelial lesion (HSIL) or cancer. The analysis was repeated with a screening study database in which colposcopic impression was assigned without knowledge of the Papanicolaou smear. Univariate and logistic regression analysis of the second database determined the relative importance of size and grade of lesion and Papanicolaou result to the accuracy of the colposcopic impression. RESULTS: In the community database, colposcopic accuracy was 60/510 (12%) when smears were ASCUS, AGUS or LSIL and 77/132 (58%) when smears were HSIL or cancer (P < .001); in the second database, it was 2/19 (11%) when smears subsequently were reported as negative, ASCUS, AGUS or LSIL and 33/65 (54%) when smears were HSIL or cancer (P < .005). An accurate colposcopic impression was seen in 5/39 (13%) women with one-quadrant lesions, 8/18 (44%) with two-quadrant lesions and 23/27 (85%) with three- or four-quadrant lesions (P < .005). None of 19 women with smears reported as negative, ASCUS, AGUS or LSIL had lesions involving three or four quadrants of the cervix, while 27/65 (42%) women with smears reported as HSIL or cancer had such lesions (P < .005). With logistic regression, the more quadrants of the cervix involved, the more accurate the colposcopic impression. Once controlled for lesion size, there was no improvement when worst histologic grade or Papanicolaou smear result was considered. CONCLUSION: Through lesions greater than CIN 2 were more often overlooked when referral smears were negative, ASCUS, AGUS or LSIL than when they were HSIL or cancer, the real reason that the lesions were not detected by colposcopy was that they were small.

Cervical cancer screening by simple visual inspection after acetic acid.

OBJECTIVE: To estimate the sensitivity and specificity of visual inspection using acetic acid as a primary screen for cervical intraepithelial neoplasia (CIN). METHODS: Visual inspection was done on 1997 women aged 35-45 years in a screening trial in rural China. Each women had colposcopy and at least five cervical biopsies (directed biopsy of lesions, one biopsy at 2, 4, 8, or 10 o'clock at the squamocolumnar junction in each normal quadrant, and an endocervical curettage). RESULTS: Forty-three women had biopsy-proven CIN II, 31 had CIN III, and 12 had invasive cancer. In two women only the endocervix was positive (one with CIN II and one with CIN III). Visual inspection yielded normal results in 1445 women (72%), low-grade intraepithelial neoplasia in 525 (26%), high-grade in 21 (1%), and cancer in six (0.3%). With abnormal visual inspection defined as low-grade intraepithelial neoplasia or worse, the sensitivity for detecting biopsy proven CIN II or worse was 71% (61 of 86, 95% confidence interval [CI] 60%, 80%); the specificity was 74% (1420 of 1911, 95% CI 72%, 76%); the sensitivity was 65% for smaller lesions (37 of 57, 95% CI 51%, 77%), and 89% for larger lesions (24 of 27, 95% CI 71%, 98%) (P =.03). CONCLUSION: The sensitivity of visual inspection equaled or exceeded reported rates for conventional cervical cytology. Visual inspection and colposcopy have similar specificity profiles for CIN II and greater. The benefit of an inexpensive point-of-care diagnosis and treatment algorithm will be a powerful incentive to pursue visual inspection for cervical cancer screening in developing countries.

Carboplatin skin testing: a skin-testing protocol for predicting hypersensitivity to carboplatin chemotherapy.

PURPOSE: A high incidence of moderate to severe hypersensitivity reactions (HRs) is noted in patients who have been treated with multiple courses of carboplatin. Presently, there is no reliable way to predict which patients may be at risk for this potentially severe adverse reaction. We developed a skin-test protocol to identify patients at high risk for HR to carboplatin chemotherapy. PATIENTS AND METHODS: Patients undergoing more than seven courses of carboplatin received a 0.02-mL intradermal injection of an undiluted aliquot of their planned carboplatin infusion 1 hour before each course of the agent. A positive skin test was prospectively defined as that resulting in a wheel of at least 5 mm with a surrounding flare. We recently reported a 27% incidence of HRs in patients receiving more than seven courses of carboplatin. These patients served as historical controls for the current study. RESULTS: Forty-seven patients with recurrent ovarian or primary peritoneal carcinoma receiving carboplatin were skin tested. Thirteen of 47 patients (28%) manifested a positive skin test at a median of nine total courses of carboplatin (range, eight to 17 courses). This rate of skin-test positivity was not significantly different from the incidence of documented HR reported in a historical control group (P =.89), suggesting comparable populations. A negative skin test accurately predicted the absence of HR in 166 of 168 courses of chemotherapy. Only two of 47 patients (4%) experienced a HR after a negative skin test. Thus, administering carboplatin only to patients with a negative skin test may result in a significant reduction in HRs relative to historical controls (P =.002). CONCLUSION: An easily performed skin test appears to predict patients in whom carboplatin may be safely administered. Treatment modifications based on the results of skin testing may reduce the incidence of HRs in patients receiving repeated courses of carboplatin.

Treatment of gynecologic cancers in pregnancy.

Gynecologic cancers are among the most common malignancies in reproductive-age women. Approximately 3% of women diagnosed with a malignancy of the reproductive tract will have a coexisting pregnancy. A pregnant woman with a gynecologic malignancy presents a significant challenge for the clinician for many reasons. Considerable diagnostic delay is common due to confusion of symptomatology with the physiologic changes associated with the pregnant state. The diagnostic options available for a patient suspected of having an invasive gynecologic malignancy may also be compromised by the pregnancy. In addition, difficult medical, ethical, and religious issues arise when the treatment of these malignancies is incompatible with continuation of the pregnancy. Unfortunately, a relatively limited experience with reproductive tract cancers in pregnancy has prevented the development of universally accepted management algorithms for many of the complex issues regarding their treatment. A literature review of diagnostic and treatment strategies for cervical, ovarian, endometrial, and vulvar carcinoma complicated by pregnancy is presented.

Treatment of relapsed carcinoma of the ovary with single-agent paclitaxel following exposure to paclitaxel and platinum employed as initial therapy.

OBJECTIVES: The aim of this study was to evaluate the ability of paclitaxel to achieve a second clinical response in patients with recurrent epithelial ovarian carcinoma who responded to standard therapy with platinum and paclitaxel in the initial setting. METHODS: Thirty-four patients with epithelial ovarian who demonstrated a complete response to paclitaxel and platinum in the initial treatment setting were retreated with paclitaxel as a single agent for relapse of their disease. Paclitaxel was given at a dose of 135-175 mg/m(2) over 3 h at 21-day intervals. Fifteen patients had platinum-resistant disease and 19 had potentially platinum-sensitive disease. Response was documented by physical examination, serial serum CA125 measurement, or radiologic evaluation. RESULTS: An objective response to paclitaxel retreatment was demonstrated in 15 patients (44%), with a median progression-free interval (PFI) of 8.6 months (range 4-17 months). An additional 14 patients (41%) demonstrated disease stabilization, with a median PFI of 7.4 months (range 3-13 months). Overall, retreatment with paclitaxel was well tolerated, with minimal cumulative toxicities, despite repetitive dosing. CONCLUSION: These results demonstrate that patients with ovarian cancer who relapse after initial treatment with paclitaxel often have disease that is still responsive to the agent. Given its relative lack of cumulative toxicity, retreatment with paclitaxel as a single agent is a reasonable therapeutic option for patients with recurrent ovarian cancer.

Safety and efficacy of adjuvant single-agent ifosfamide in uterine sarcoma.

PURPOSE: The role of adjuvant therapy for completely resected uterine sarcoma continues to be debated. Previous chemotherapy trials have shown little, if any, advantage over surgery alone, with significant added toxicity. To our knowledge, the current study is the first to evaluate adjuvant ifosfamide in completely resected uterine sarcomas. METHODS: Between 1992 and 1999, 13 consecutive patients with completely resected moderate- to high-grade uterine sarcoma received three cycles of adjuvant ifosfamide (1.5 g/m(2)/day x 3 days, repeated every 28 days). Mesna was given 30 min prior to infusion. Postinfusion mesna was administered to 10 of the patients in the outpatient setting utilizing a subcutaneous infusion pump. The remaining 3 patients received traditional intravenous mesna at 4 and 8 h after infusion. RESULTS: The median follow-up of the patient population was 26 months. For early-stage patients (n = 10), the 2-year progression-free survival was 60%, with a median of 26 months. The 2-year overall survival was 100%, dropping to 67% at 3 years. Early-stage patients showed an advantage in both progression-free and overall survival. Early-stage patients with mixed müllerian tumor (MMT) had a significantly longer time to progression that those with leiomyosarcoma (LMS) (2-year progression-free survival of 100% versus 33%; P = 0.019). Three patients required dose reduction secondary to grade 2-3 toxicities (neutropenia x2, nausea and vomiting x1). All significant toxicity was eliminated with dose reduction. CONCLUSIONS: Adjuvant ifosfamide appears to be safe and well tolerated in patients with completely resected uterine sarcoma. It can easily be given in the outpatient setting if mesna is administered via a subcutaneous pump. Our data, consistent with previous studies in advanced sarcoma, suggest a potentially greater role for ifosfamide in MMT than in LMS.

The use of paclitaxel and platinum-based chemotherapy in uterine papillary serous carcinoma.

OBJECTIVE: Uterine papillary serous carcinoma (UPSC) is an aggressive malignancy with a histologic appearance and pattern of spread that resembles that of papillary serous adenocarcinoma of the ovary. The current standard therapy for advanced ovarian cancer, cisplatin or carboplatin plus paclitaxel, results in high objective response rates for that tumor. This regimen has thus far not been evaluated in UPSC. METHODS: Twenty-four patients with UPSC treated with platinum-based chemotherapy and paclitaxel were retrospectively evaluated. Eighteen patients received these agents in the adjuvant setting (n = 9) or for disease persistent after initial surgical management (n = 9). Eleven patients received one or more courses of this drug combination for recurrent disease, 5 of whom had prior exposure in the initial setting. RESULTS: Mean follow-up was 35 months (range 6-72+). A median progression-free interval (PFI) of 30 months (range 8-61+) was seen in patients treated in the adjuvant setting. Objective response, indicated by normalization of an elevated prechemotherapy CA125 level, was seen in 8 of 9 patients treated for residual disease after initial surgery (median PFI of 13 months, range 5-38+). Objective response of both measurable and/or evaluable disease was seen in 7 of 11 patients treated for recurrent disease (median PFI of 9 months, range 4-18). Six patients had retreatment with one or both agents and 4 responded a second time. Overall, the regimen was well tolerated. CONCLUSION: Paclitaxel and platinum-based chemotherapy has demonstrated activity in UPSC with acceptable toxicity. These results merit further investigation of the possible role of these agents in patients with this aggressive histologic subtype.

Risk factors for endometrial hyperplasia and cancer among women with abnormal bleeding.

OBJECTIVE: To identify independent risk factors for endometrial neoplasia in women with abnormal perimenopausal or postmenopausal bleeding and to use those factors to develop and test a predictive model. METHODS: We conducted a case-control study of women with abnormal perimenopausal or postmenopausal bleeding who had endometrial samplings; cases had endometrial cancer or complex hyperplasia and controls had benign endometrial histologies. Multivariate logistic regression models identified factors associated with risks of endometrial neoplasia. The predictive abilities of our models and a published model were assessed using the area under receiver operating characteristic (ROC) curves, for which an area of 1.0 indicated perfect positive predictive ability and an area of 0.5 was expected by chance. RESULTS: There were 57 cases of endometrial hyperplasia or cancer and 137 controls. Parity was related inversely (odds ratio [OR] 0.70; 95% confidence interval [CI] 0.56, 0.88; P = .002) and weight directly (OR 1.02 per kg; 95% CI 1.01, 1.04; P = .018) to the risk of endometrial neoplasia. Age (OR 1.04 per year; 95% CI 1.00, 1.08; P = .06) and diabetes (OR 3.50; 95% CI 0.99, 12.33; P = .052) were significant marginally. The area under the ROC curve for our model was 0.75, indicating moderate predictive ability; the area under the ROC curve for the published model was lower at 0.66. CONCLUSION: Current clinical predictive models based on case-control studies do not have sufficient predictive ability to determine if women with abnormal perimenopausal or postmenopausal bleeding should have diagnostic testing.