CIN III lesions and regression: retrospective analysis of 635 cases.

BACKGROUND: The rate of spontaneous regression in CIN III lesions is controversial. Whereas some studies have reported high regression rates of up to 38% after prolonged biopsy-conus intervals, others have shown rates between 0 and 4% without considering time intervals. Identification of young patients with potentially regressing CIN III could offer the chance to avoid conisation, thus lowering the risk of preterm labour. METHODS: To further clarify the facts, we retrospectively compared 635 biopsies showing CIN III with the diagnosis of the conisation. Either regression (CIN I or less) or non-regression (CIN II and higher) was recorded. Diagnoses were made by light microscopy and p16 immunostaining. RESULTS: Conisation was performed between 2 and 463 days after biopsy (median 8.9 weeks). Six hundred twenty one (98%) were HPV-HR positive. In 345 cases, HPV subtyping was available, showing HPV16 infection in 57%. Routine processing of the conisation tissue showed no corresponding CIN lesion (< CIN II) in 40 cases (6.3%). Additional step sectioning of the tissue revealed small CIN II+ lesions in 80%. Finally, eight cases (1.3%) fulfilled the criteria of regression. No regression was seen in HPV16 positive cases. Twelve invasive carcinomas were detected by routine processing of the conisation tissue. CONCLUSION: These results are in contrast with some prior reports that might have overestimated spontaneous regression of CIN III. Study size and an accurate discrimination between CIN II and CIN III lesions by histopathology seem to be the most likely factors to explain the diverging results published. Complete step sectioning of the whole tissue is also mandatory in questionable cases. Although theories exist that the initial biopsy might stimulate the immune system, thus triggering regression within weeks, our data do not substantially support such a mechanism. Overall, the chance of a CIN III lesion to regress rapidly within weeks or months after diagnosis seems to be small. We found more previously undetected invasive cancer than we observed regression. Therefore, a change in the current policy to treat CIN III lesions is unwarranted.

Screening for cervical cancer precursors with p16/Ki-67 dual-stained cytology: results of the PALMS study.

BACKGROUND: Pap cytology is known to be more specific but less sensitive than testing for human papillomavirus (HPV) for the detection of high-grade cervical intraepithelial neoplasia (CIN2+). We assessed whether p16/Ki-67 dual-stained cytology, a biomarker combination indicative of transforming HPV infections, can provide high sensitivity for CIN2+ in screening while maintaining high specificity. Results were compared with Pap cytology and HPV testing. METHODS: A total of 27,349 women 18 years or older attending routine cervical cancer screening were prospectively enrolled in five European countries. Pap cytology, p16/Ki-67 immunostaining, and HPV testing were performed on all women. Positive test results triggered colposcopy referral, except for women younger than 30 years with only positive HPV test results. Presence of CIN2+ on adjudicated histology was used as the reference standard. Two-sided bias-corrected McNemar P values were determined. RESULTS: The p16/Ki-67 dual-stained cytology positivity rates were comparable with the prevalence of abnormal Pap cytology results and less than 50% of the positivity rates observed for HPV testing. In women of all ages, dual-stained cytology was more sensitive than Pap cytology (86.7% vs 68.5%; P < .001) for detecting CIN2+, with comparable specificity (95.2% vs 95.4%; P = .15). The relative performance of the tests was similar in both groups of women: younger than age 30 and 30 years or older. HPV testing in women 30 years or older was more sensitive than dual-stained cytology (93.3% vs 84.7%; P = .03) but less specific (93.0% vs 96.2%; P < .001). CONCLUSIONS: The p16/Ki-67 dual-stained cytology combines superior sensitivity and noninferior specificity over Pap cytology for detecting CIN2+. It suggests a potential role of dual-stained cytology in screening, especially in younger women where HPV testing has its limitations.