Performance of p16/Ki67 Immunostaining for Triage of Elderly Women with Atypical Squamous Cells of Undetermined Significance.

BACKGROUND: The p16/Ki67 technique has been poorly studied in postmenopausal women with ASC-US cytology. The objective of this study was to compare the accuracy of p16/Ki67 staining, HPV testing and HPV 16 genotyping for the identification of CIN2 + lesions in postmenopausal women with ASC-US cytology. METHOD: A total of 324 postmenopausal women with positive ASC-US were included. The women underwent HPV test, colposcopy, and biopsy. The slides were discolored and then stained with the CINtec Plus Kit for p16/Ki67. The HPV test results were classified as HPV16 +, hrHPV+ (other hrHPV genotypes), or HPV negative. RESULTS: The p16/Ki67 sensitivity for CIN2+ was 94.5%, the specificity 86.6%, PPV of 59% and NPV of 95.9%. The HPV test showed a sensitivity of 96.4% for CIN2+, a specificity of 62.8%, a PPV of 35% and a NPV of 98.8%. In postmenopausal women, the prevalence of genotype 16 decreases in favor of the other high-risk genotypes. CONCLUSION: Given the low sensitivity of cytology and the low percentage of HPV16-positive cancers among elderly women, triage via cytology and genotyping is not the best strategy; double staining cytology shows high profiles of sensibility and specificity for CIN2+ in ASCUS postmenopausal women.

Spontaneous regression of cervical intraepithelial neoplasia 3 in women with a biopsy-cone interval of greater than 11 weeks.

BACKGROUND: Although there is broad consensus that only a subset of CIN3 will progress to cancer, there is currently no surefire way to predict which CIN3 will regress. Understanding the natural history of CIN3 is important, and finding markers for progression or regression could improve treatment strategies. According to the guidelines of the American Society for Colposcopy and Cervical Pathology of 2006, positive CIN3 p16 in women should be managed with excisional treatment (LEEP). For ethical reasons we cannot fail to treat women with CIN3 in order to study their regression capacity so we conducted a retrospective study to evaluate the regression rate of CIN3 diagnosed with a biopsy by studying the histological result of the cone removed by LEEP. We also investigated age, HPV genotypes and biopsy-cone interval distance as possible regression factors. METHODS: We selected 171 women with a histological diagnosis of positive CIN3 p16 as an entry criterion. All patients underwent LEEP / biopsy. A histological diagnosis of the cone of CIN3 or higher was considered as persistence or progression, the diagnosis of CIN1 or lower was considered as regression of the lesion. We used out a logistic model to study the probability of spontaneous regression of CIN3 as a function of the patient's age, the time elapsed between the biopsy and the cone (in weeks) and the HPV genotype. RESULTS: We found that the spontaneous regression rate of CIN3 was 15,8%, which was strongly associated with the biopsy-cone interval > 11 weeks. Genotype 16, the most represented, was present both in cases of regression (77.8%) and in persistence (83.3%). Regarding age, the estimated odds ratio of the probability of observing a regression in women over 25 years of age was 0.0045 times that of women under 25 years of age (CI: 0.00020, 0.036). Neither age nor viral genotype are significant as predictors of regression. CONCLUSION: To wait at least 11 weeks from the biopsy before subjecting the woman to LEEP could prevent unnecessary LEEP procedures, considering also that from CIN3 to carcinoma it takes years before the neoplastic transformation takes place.

Possible role of negative human papillomavirus E6/E7 mRNA as a predictor of regression of cervical intraepithelial neoplasia 2 lesions in hr-HPV positive women.

BACKGROUND: The aim of this study was to evaluate the regression rate of CIN2 p16 positive lesions in women over 25 years of age and identify possible predictors of regression. METHODS: A total of 128 CIN2 p16 positive patients over 25 years old were considered. The women met the following inclusion criteria: HPV genotype 16, 18, 31, 33, 45 positive, HPV E6 / E7 mRNA test positive, without immune system pathologies, not pregnant and had completed at least two years of follow-up. At each follow-up examination patients were examined by colposcopy, HPV test, E6/E7mRNA, targeted biopsy and p16 protein detection. The final state after the two years of follow-up was classified as progression if the histology showed a CIN3, persistence if the lesion was a CIN2, regression if negative or LSIL. The predicted regression factors evaluated were: HPV E6/E7mRNA, protein p16. RESULTS: Overall, we had 35.1% (45 cases) of progression to CIN3, 41.4% (53 cases) of persistence and 23.4% (30 cases) of regression. The regression rate was higher in women with negative mRNA 92.8% (26/28), OR 312 (34.12-1798.76) p = 0.0001, while women with p16 negative had a regression of 22.6% (7/31), OR 0.94 (95% CI 0.36-2.46), p was not significant. We found no significant difference in regression between p16 positive (23.7%) and p16 negative (22.6%) CIN2 p16 lesions. p16 had a VPN of 22.6 (CI 95% 0.159-0.310), indicating that a p16 negative lesion does not exclude a CIN2 + . CONCLUSIONS: We had a regression rate of 23.4%, which was low if we consider that in the literature the regression rates vary from 55 to 63%. The discrepancy in the results may indeed be explained by the fact that all lesions in our study were hr-HPV positive and belonged to "older women" reflecting a more "high-risk" population. As regression factors we studied p16 and HPV E6/E7 mRNA. The results of our study show that HPV mRNA, if negative, appears to be able to identify CIN2 lesions with a higher probability of regression and underlines how a p16 negative is not an indicator of regression.