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The detection of circulating tumor cells (CTCs) is an emerging strategy for the early detection, prognostication, and identification of recurrent cancer. The clinical utility of CTC detection has been established, but few studies have employed this strategy for the detection of gynecologic cancers. Here, we present a novel, biochip-based microfluidic device for the detection of CTCs in gynecologic cancers. The study cohort included three patients with cervical cancer, eight with endometrial cancer, two with ovarian cancer, two with breast cancer, and one with vaginal small cell carcinoma. Four cancer type-specific molecular markers (PanCK, GATA3, HER2, and HE4), as well as CD13, were used for prognostication and recurrence detection, along with downstream genomic analysis. GATA3 and HER2 were markedly expressed in the patients with cervical cancer, and this expression was strongly correlated with the early detection of recurrent disease. All four molecular markers were expressed preoperatively in the patients with endometrial cancer, and the re-expression of different markers was observed at follow-up before recurrence was confirmed. CD13 was identified as an alternative prognostic marker for both cervical and endometrial cancer. Our pilot study indicated that the novel CTC detection system can be used for prognostication and early detection of disease recurrence, which needed further investigation.

Background: During follow-up for patients with cervical carcinoma, elevation of serum squamous cell carcinoma antigen (SCC-Ag) levels in the absence of detectable recurrent lesions presents a diagnostic and therapeutic challenge. In the current prospective study, the authors evaluated the use of fluorine-18-labeled fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) to detect disease recurrence in this setting., Methods: Women with cervical carcinoma who experienced complete responses to primary treatment or salvage therapy and who had no evidence of recurrent disease as detected by conventional methods but had serum SCC-Ag levels > or = 2.0 ng/mL on 2 consecutive occasions were eligible for the study. PET was performed within 2 weeks after the completion of conventional studies for the assessment of recurrence., Results: Twenty-seven consecutive patients were registered for the current study. PET findings were positive for 19 patients: 14 who had a distant lesion or lesions, 2 who had a local lesion or lesions, and 3 who had both local and distant lesions. Of these 19 patients, 17 were confirmed to have recurrent disease; the remaining two were found to be free of disease but had severe anthracosis in the PET-positive mediastinal lymph nodes. Seven of the eight patients with negative PET findings were not found to have recurrent disease on follow-up. Overall, PET detected FDG-avid lesions in 17 (94%; P < 0.001) of the 18 patients with recurrent disease. Seven of these 18 patients received therapy with curative intent; complete control was achieved in 6, four of whom currently are alive and free of disease. The addition of PET in the current setting curbed the use of futile curative therapy and significantly increased overall survival for patients in the current cohort compared with a historical group of 30 consecutive patients who had elevated SCC-Ag levels as a first sign of recurrence., Conclusions: PET expedited the detection of recurrent cervical carcinoma in patients with unexplained elevation of SCC-Ag levels. Such expedited detection may have positive effects on patient survival., (Copyright 2004 American Cancer Society.)

Objective: To evaluate the histologic nature of low grade intraepithelial lesion (LSIL) in a region with a high prevalence of invasive cervical carcinoma and to propose a management protocol., Study Design: Comparing the follow-up of 877 women with LSIL during a 43-month period, taking into consideration the histologic nature determined by colposcopic biopsy, endocervical curettage, conization or hysterectomy as the final pathologic diagnosis., Results: During the study period, from July 1994 to February 1998, a total of 128,925 Pap smears were performed at our institute, with 877 (0.68%) diagnosed as LSIL. Among these, 722 women with CIN1-SIL and 32 with human papillomavirus-related changes (HPV-SIL) were enrolled in the study. Of the 543 women with CIN 1/squamous intraepithelial lesion, 145 (27%) cases of high grade squamous intraepithelial lesion were disclosed histologically, as were 16 (3%) cases of microinvasion. Among those followed at an interval of three months with a Pap smear alone, the persistence rate was 46.8%, while the regression rate was 40%. Thirty-two women with HPV/SIL underwent histologic evaluation, revealing 18% CIN 2/3 with no microinvasion., Conclusion: A high percentage of CIN 2/3 as well as microinvasive lesions will go unnoticed in the absence of colposcopic evaluation.

Objective: To determine whether high-risk human papillomavirus (HPV) DNA testing could improve the detection of cervical intraepithelial neoplasia (CIN) and cancer in older women (> or = 50 years old) with mildly abnormal results on conventional cytology., Study Design: The study was based on 119 patients aged over 50 (median, 62; range, 50-78) referred for colposcopy with Pap smears reported as atypical squamous cells of undetermined significance (ASCUS) or low grade squamous intraepithelial lesion (LSIL) from February 1997 to September 1998. The presence of high-risk HPV DNA (including HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68) was determined with the Hybrid Capture II (Digene, Inc., Silver Spring, Maryland) microplate method. Cytologic examination by Pap smear was based on the Bethesda System and, cervical biopsy was done via colposcopy., Results: High-risk HPV DNA was demonstrated in 75.6% (34/45) of patients with LSIL and 52.7% (39/74) with ASCUS. Those who were HPV positive were significantly more likely to have CIN or cancer (odds ratio, 33.40; 95% confidence interval, 11.89-93.97; P < .0001). The sensitivity of HPV assay for detection of lesions more severe than CIN 2 was 100%, specificity 64.8%, positive predictive value 66.7% and negative predictive value 100%., Conclusion: The addition of a high-risk HPV DNA assay to cytologic examination appears to provide excellent sensitivity and negative predictive value for early detection of high grade CIN or cancer in older women with minimally abnormal Pap smears.