Four conserved amino acids on human papillomavirus E6 predict clinical high‐risk types.

Human papillomavirus (HPV) types included in the genus alpha papillomavirus (alpha‐HPVs) are subdivided into high‐ and low‐risk HPVs associated with tumorigenicity. According to conventional risk classification, over 30 alpha‐HPVs remain unclassified and HPV groups phylogenetically classified using the L1 gene do not exactly correspond to the conventional risk classification groups. Here, we propose a novel cervical lesion progression risk classification strategy. Using four E6 risk distinguishable amino acids (E6‐RDAAs), we successfully expanded the conventional classification to encompass alpha‐HPVs and resolve discrepancies. We validated our classification system using alpha‐HPV‐targeted sequence data of 325 cervical swab specimens from participants in Japan. Clinical outcomes significantly correlated with the E6‐RDAA classification. Four of five HPV types in the data set that were not conventionally classified (HPV30, 34, 67, and 69) were high‐risk according to our classification criteria. This report sheds light on the carcinogenicity of rare genital HPV types using a novel risk classification strategy. [ABSTRACT FROM AUTHOR]