To compare test performance characteristics of conventional Pap tests and liquid-based cervical cytology samples. Eligible studies, published between 1991 and 2007, were retrieved through PubMed/EmBase searching and completed by consultation of other sources. Studies were selected if a conventional and a liquid-based sample were prepared from the same woman or when one or the other type of sample was taken from a separate but similar cohort. The current systematic review and meta-analysis is restricted to studies where all subjects were submitted to gold standard verification, based on colposcopy and histology of colposcopy-targeted biopsies, allowing computation of absolute and relative test validity for cervical intraepithelial neoplasia grade 2 or worse. Randomized trials were selected as well if all test-positive cases were verified with the same gold standard, allowing computation of the relative sensitivity. Impact of study characteristics on accuracy was assessed by subgroup meta-analyses, meta-regression, and summary receiver operating characteristic curve regression. The relative sensitivity, pooled from eight studies, with complete gold standard verification and from one randomized clinical trial, did not differ significantly from unity. Also, the specificity, considering high-grade and low-grade squamous intraepithelial lesions as cutoff, was similar in conventional and liquid cytology. However, a lower pooled specificity was found for liquid-based cytology when presence of atypical squamous cells of undetermined significance was the cutoff (ratio 0.91, 95% confidence interval 0.84-0.98). Differences in study characteristics did not explain interstudy heterogeneity. Liquid-based cervical cytology is neither more sensitive nor more specific for detection of high-grade cervical intraepithelial neoplasia compared with the conventional Pap test.

Two separate pathways leading to vulvar carcinoma have been suggested. First, a human papillomavirus (HPV)-dependent pathway, in which premalignant stages of vulvar cancer are the classic vulvar intraepithelial neoplasia (VIN) lesions. Second, an HPV-independent pathway, associated with differentiated VIN III lesions and/or lichen sclerosus. To obtain insight into the mechanisms underlying these pathways, we determined the relationship between HPV DNA and the expression of p14ARF and p16INK4A in non- and (pre)malignant vulvar lesions. Seventy-three archival samples of non- and (pre)neoplastic vulvar lesions were selected and tested for hr-HPV DNA using a broad-spectrum HPV detection/genotyping assay (SPF10-LiPA) and the expression of p14ARF and p16INK4A. The prevalence of HPV increased with the severity of the classic VIN lesions; in VIN I no hr-HPV was detected, in VIN II 43%, and in VIN III 71% of the samples were hr-HPV-positive. Roughly the same was true for the expression of p14ARF and p16INK4A. The simultaneous expression of p14ARF and p16INK4A was highly associated with the presence of hr-HPV DNA. Hr-HPV was detected in only a single case of the differentiated VIN III lesions, whereas no expression of p14ARF was found and 16INK4A was present in only two cases. All 16 samples of vulvar cancer were hr-HPV DNA- negative, although in respectively 63% and 25%, p14ARF and p16INK4A was expressed. No relation was found between hr-HPV and the expression of p14ARF and p16INK4A in the 20 nonneoplastic vulvar lesions. Our results provide further evidence that vulvar squamous cell carcinoma is a multifactorial disease that develops from two different pathways. First, an HPV-dependent pathway with a remarkable resemblance to CIN lesions and cervical carcinoma and second, an HPV-independent pathway in which differentiated VIN III lesions that are hr-HPV-negative may be precursors.

Background Despite the excellent prognosis of Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) stage I, type I endometrial cancers, a substantial number of patients experience recurrence and die from this disease. We analyzed the value of immunohistochemical L1CAM determination to predict clinical outcome. Methods We conducted a retrospective multicenter cohort study to determine expression of L1CAM by immunohistochemistry in 1021 endometrial cancer specimens. The Kaplan–Meier method and Cox proportional hazard model were applied for survival and multivariable analyses. A machine-learning approach was used to validate variables for predicting recurrence and death. Results Of 1021 included cancers, 17.7% were rated L1CAM-positive. Of these L1CAM-positive cancers, 51.4% recurred during follow-up compared with 2.9% L1CAM-negative cancers. Patients bearing L1CAM-positive cancers had poorer disease-free and overall survival (two-sided Log-rank P < .001). Multivariable analyses revealed an increase in the likelihood of recurrence (hazard ratio [HR] = 16.33; 95% confidence interval [CI] = 10.55 to 25.28) and death (HR = 15.01; 95% CI = 9.28 to 24.26). In the L1CAM-negative cancers FIGO stage I subdivision, grading and risk assessment were irrelevant for predicting disease-free and overall survival. The prognostic relevance of these parameters was related strictly to L1CAM positivity. A classification and regression decision tree (CRT)identified L1CAM as the best variable for predicting recurrence (sensitivity = 0.74; specificity = 0.91) and death (sensitivity = 0.77; specificity = 0.89). Conclusions To our knowledge, L1CAM has been shown to be the best-ever published prognostic factor in FIGO stage I, type I endometrial cancers and shows clear superiority over the standardly used multifactor risk score. L1CAM expression in type I cancers indicates the need for adjuvant treatment. This adhesion molecule might serve as a treatment target for the fully humanized anti-L1CAM antibody currently under development for clinical use.

Research from JAMA — Comparison of Liquid-Based Cytology With Conventional Cytology for Detection of Cervical Cancer Precursors — A Randomized Controlled Trial

OBJECTIVE: To assess the agreement between preoperative endometrial sampling and final diagnosis for tumor grade and subtype in patients with endometrial carcinoma. DATA SOURCES: MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane library were searched from inception to January 1, 2017, for studies that compared tumor grade and histologic subtype in preoperative endometrial samples and hysterectomy specimens. METHODS OF STUDY SELECTION: In eligible studies, the index test included office endometrial biopsy, hysteroscopic biopsy, or dilatation and curettage; the reference standard was hysterectomy. Outcome measures included tumor grade, histologic subtype, or both. TABULATION, INTEGRATION, AND RESULTS: Two independent reviewers assessed the eligibility of the studies. Risk of bias was assessed (Quality Assessment of Diagnostic Accuracy Studies). A total of 45 studies (12,459 patients) met the inclusion criteria. The pooled agreement rate on tumor grade was 0.67 (95% CI 0.60–0.75) and Cohen's κ was 0.45 (95% CI 0.34–0.55). Agreement between hysteroscopic biopsy and final diagnosis was higher (0.89, 95% CI 0.80–0.98) than for dilatation and curettage (0.70, 95% CI 0.60–0.79; P=.02); however, it was not significantly higher than for office endometrial biopsy (0.73, 95% CI 0.60–0.86; P=.08). The lowest agreement rate was found for grade 2 carcinomas (0.61, 95% CI 0.53–0.69). Downgrading was found in 25% and upgrading was found in 21% of the endometrial samples. Agreement on histologic subtypes was 0.95 (95% CI 0.94–0.97) and 0.81 (95% CI 0.69–0.92) for preoperative endometrioid and nonendometrioid carcinomas, respectively. CONCLUSION: Overall there is only moderate agreement on tumor grade between preoperative endometrial sampling and final diagnosis with the lowest agreement for grade 2 carcinomas.