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Background  Persistent infection with human papillomaviruses (HPVs) has been associated with cervical intraepithelial neoplasia (CIN) and cervical cancer. However, why only a fraction of HPV cases progress to cancer is still unclear.    Methods  We focused on the heterogeneity, classification, evolution and dispersal of variants for 14 common HPV types in 262 HPV-positive patients with cervical lesions. The  E6  and  E7  genes of HPV were sequenced and compared with the HPV reference for sequence analysis. Phylogenetic trees were constructed using the neighbour-joining tree method with MEGA 7.0.    Results  In this study, 233  E6  and 212  E7  sequences were successfully amplified by PCR, and these sequences were divided into 5 species groups: alpha-9 (HPV16, 31, 33, 52, 58), alpha-5 (HPV51), alpha-6 (HPV53, 66), alpha-7 (HPV18, 39, 59, 68) and alpha-10 (HPV6, 44). The incidence of high-grade squamous intraepithelial lesion (HSIL) in patients infected with alpha-9 HPV was significantly increased compared with other groups ( P  < 0.0001), especially HPV16 ( P  < 0.0001). Strikingly,  E7  had significantly fewer nonsynonymous variants in the HSIL compared to <HSIL groups ( P  = 3.17× 10 − 4 ). The A388C (K93 N) variation in HPV58  E6  can significantly reduce the risk of HSIL ( P  = 0.015). However, T7220G (D32E) variation in HPV16  E6  and A7689G (N29S) in HPV16  E7  increased the incidence of HSIL compared to the <HSIL group ( P  = 0.036 and 0.022).    Conclusions  Strict conservation of E7 is important for HPV carcinogenicity, especially N29 of HPV16. The findings in this work provide preventative/therapeutic interventions for HPV infections and CIN.

infectious agents and cancer

Phylogeny and polymorphism in the E6 and E7 of human papillomavirus: alpha-9 (HPV16, 31, 33, 52, 58), alpha-5 (HPV51), alpha-6 (HPV53, 66), alpha-7 (HPV18, 39, 59, 68) and alpha-10 (HPV6, 44) in women from Shanghai