High-Risk Genotypes of Human Papillomavirus at Diverse Anogenital Sites among Chinese Women: Infection Features and Potential Correlation with Cervical Intraepithelial Neoplasia

Simple Summary Cervical cancer is one of the most prevalent cancers among women. However, the clinically well-accepted cervical HPV 16/18 test was not sufficient to screen patients with high-grade cervical intraepithelial neoplasia (CIN 2+). The purpose of this study was to investigate the infection features of 15 high-risk (HR) HPVs in cervix, vagina, vulva, and anus, and evaluate their potential association with cervical lesions. In this study, HPV genotyping was performed on samples from the four anogenital sites of 499 Chinese women. Results showed that in addition to the well-recognized cervical-cancer-associated subtypes, e.g., HPV 16, 52, and 58, HPV 51, 53, and 56 had high prevalence and site-related infection consistency among the anogenital sites studied. In addition to cervical HPV 16/18, cervical HPV 33/35/52/53/56/58 were suggested as potential indicators that could improve the accuracy of HR-HPV screening in predicting CIN 2+.Abstract Background: Both cervical cancer and cervical intraepithelial neoplasia (CIN) are associated with human papillomavirus (HPV) infection at different anogenital sites, but the infection features of high-risk (HR) HPVs at these sites and their association with cervical lesions have not been well characterized. Given the limitation of cervical HPV 16/18 test in screening patients with high-grade CIN (CIN 2+), studies on whether non-16/18 HR-HPV subtype(s) have potential as additional indicator(s) to improve CIN 2+ screening are needed. Methods: The infection of 15 HR-HPVs in vulva, anus, vagina, and cervix of 499 Chinese women was analyzed, and CIN lesion-associated HR-HPV subtypes were revealed. Results: In addition to the well-known cervical-cancer-associated HPV 16, 52, and 58, HPV 51, 53, and 56 were also identified as high-frequency detected subtypes prevalently and consistently present at the anogenital sites studied, preferentially in multi-infection patterns. HPV 16, 52, 58, 56, and 53 were the top five prevalent subtypes in patients with CIN 2+. In addition, we found that cervical HPV 33/35/52/53/56/58 co-testing with HPV 16/18 might improve CIN 2+ screening performance. Conclusion: This study provided a new insight into HR-HPV screening strategy based on different subtype combinations, which might be used in risk stratification clinically.