HPV16 genetic variation and the development of cervical cancer worldwide

Background: Factors that favour a small proportion of HPV16 infections to progress to cancer are still poorly understood, but several studies have implicated a role of HPV16 genetic variation. Methods: To evaluate the association between HPV16 genetic variants and cervical cancer risk, we designed a multicentre case-control study based on HPV16-positive cervical samples (1121 cervical cancer cases and 400 controls) from the International Agency for Research on Cancer biobank. By sequencing the E6 gene, HPV16 isolates were classified into variant lineages and the European (EUR)-lineage isolates were subclassified by the common polymorphism T350G. Results: Incidence of variant lineages differed between cases and controls in Europe/Central Asia (P = 0.006, driven by an underrepresentation of African lineages in cases), and South/Central America (P = 0.056, driven by an overrepresentation of Asian American/North American lineages in cases). EUR-350G isolates were significantly underrepresented in cervical cancer in East Asia (odds ratio (OR) = 0.02 vs EUR-350T; 95% confidence interval (CI) = 0.00-0.37) and Europe/Central Asia (OR = 0.42; 95% CI = 0.27-0.64), whereas the opposite was true in South/Central America (OR = 4.69; 95% CI = 2.07-10.66). Conclusion: We observed that the distribution of HPV16 variants worldwide, and their relative risks for cervical cancer appear to be population-dependent.