HPV-negative high-grade cervical precancerous lesions or invasive cancer in China: A post hoc analysis of a multicentric clinical study

ObjectiveTo evaluate HPV-negative cervical high-grade precancerous lesions or cancer in China. MethodsHistologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) were searched in a multicentric clinical study. All patients underwent cobas HPV testing, liquid-based cytology, DNA ploidy analysis, and colposcopy-guided biopsy. According to clinical practice, patients underwent p16(ink4a) staining and cone biopsy. Comparisons were made between HPV-negative and -positive patients for clinical characteristics. ResultsThe study found 61 cases of cobas HPV-negative CIN2+ among 797 cases of histologically confirmed CIN2+, including 38 CIN2, 20 CIN3, and 3 invasive cancers. The prevalence of HPV-negative CIN2+ and CIN3+ was 7.7% (95% confidence interval [CI] 5.8-9.5) and 5.7% (95% CI 3.5-8.0), respectively. Among 24 cases with p16 staining, 20 showed p16 positivity. The proportions of normal or minor abnormalities in terms of colposcopy, cytology, and DNA ploidy were higher in HPV-negative cases than in HPV-positive cases. When adding cytology to the screening of symptomatic or previously HPV-positive women, the prevalence of HPV-negative CIN2+ or CIN3 would decrease by approximately 50%. ConclusionLess than one-tenth of CIN2+ are missed by HPV-only screening, and they have smaller lesions than HPV-positive cases. Colposcopy should be considered for symptomatic or previously HPV-positive women with HPV-negative results.