Genotype profile of HPV in ASC‐H cytology and histologic follow‐up—prevalence, distribution, and risk: A retrospective study of 1414 cases

Abstract Background A cytologic diagnosis of atypical squamous cells, cannot exclude high‐grade squamous lesion (ASC‐H) poses a disproportionately high risk of cervical cancer development. The objective of this study was to analyze type‐specific risks by mapping human papillomavirus (HPV) genotypes in ASC‐H cytology. Methods In total, 1,048,581 Papanicolaou tests that had ASC‐H cytology were retrieved. Concurrent HPV genotyping using proprietary multiplex real‐time (MRT) and polymerase chain reaction (PCR) HPV tests and histologic follow‐up findings were analyzed. Results Among 1678 patients who had ASC‐H findings (0.16%), 1414 (84.3%) underwent concurrent HPV genotyping (MRT, 857; HPV PCR test, 557). The overall high‐risk HPV (hrHPV)‐positive rate was 84.4%. Of the 857 MRT cases, 63.9% were infected with a single hrHPV, and 24.4% had multiple genotypes. The most prevalent HPV types were HPV16/52/58/33/31. Lesions that were identified as cervical intraepithelial neoplasia 2 or worse (CIN2+) were detected in 498 of 906 cases (55.0%), including 81 cervical carcinomas (8.9%). The risk of CIN2+ for the composite group of HPV16/52/58/33/31‐positive cases was 62.7%, representing 90.7% (264 of 291) of total CIN2+ lesions in ASC‐H/hrHPV–positive cases by MRT. CIN2+ lesions were detected in 108 of 142 (76.1%) HPV16‐positive and/or HPV18‐positive women by the PCR the HPV test. Among 128 hrHPV‐negative ASC‐H cases by both methods, CIN2+ lesions were identified in 21 of 128 (16.4%), including five cervical carcinomas (3.9%). The sensitivity, specificity, positive predictive value, and negative predictive value for patients in the composite group with HPV16/52/58/33/31 were 88.0%, 40.8%, 62.7%, and 75.0%, respectively. Conclusions Papanicolaou tests classified as ASC‐H are associated with a high CIN2+ rate and warrant colposcopy, regardless of HPV status. The extent to which the risk‐stratification provided by comprehensive HPV genotyping can inform the management of ASC‐H cytology remains to be explored.