Next-generation sequencing for typing human papillomaviruses and predicting multi-infections and their clinical symptoms.

Human papillomavirus (HPV) has more than 100 different types, some of which are associated with cancer. The most common example is that of cervical cancer, which is associated with HPV16 and HPV18. Here, we performed next-generation sequencing (NGS) to type 2436 samples obtained from Korean women to elucidate the correlation between multiple infections, virus types, and cytology. NGS revealed that types 58, 56, and 16 were the most common in high-risk (HR) types, whereas types 90, 54, and 81 were the most common in low-risk (LR) types. The incidence of atypical squamous cells of undetermined significance (ASCUS) or high-grade squamous intraepithelial lesion (HSIL) was 11.45% in single-type cases and 27.17% in multiple infections by the two types of HPV. ASCUS or HSIL was 29.79% in only the HR type multiple infections and 29.81% in mixed high- and low-risk types of multiple infections, whereas it was 18.79% in LR type multiple infections (P ≤ 0.0001). Co-infection by LR-HPV and HR-HPV is therefore more likely to cause cell lesions. Collectively, these results show that the higher the incidence of multiple infections, the greater the frequency of cell lesions. Thus, to predict the clinical symptoms, it would be beneficial to confirm the HPV type and multiple infections using NGS, although this could be relatively expensive.