The majority of human papillomavirus (HPV) belong to the genus alpha-papillomavirus, which can be further subdivided into species and then strains. Approximately 200 strains of HPV have been identified, and the whole genomes of approximately 100 strains have been (discovered) and completely sequenced. Between 13 and 18 HPV strains have been characterized as conferring a high oncogenic risk, with 12 of these strains belonging to the HPV species 7 (HPV-18, -39, -45, -59, -68) and species 9 (HPV-16, -31, -33, -35, -52, -58, -67). While strains belonging to the same species are phylogenetically related, they may differ biologically. The available data on whether natural HPV infection infers cross protection against other related strains from the same species are equivocal. There are data to indicate that following HPV infection, there appears to be a reduced risk of contracting the same strain of HPV. However, there is also evidence to indicate that natural infection with HPV does not confer group-specific immune protection or general protection from reinfection with genital HPV mucosal types. Recent studies conducted with HPV vaccines show data on cross-protection against related HPV strains. In vitro experiments with serum from recipients of the quadrivalent HPV vaccine (HPV-6/8/16/18) show neutralization of HPV 45 pseudovirions. Cross-protection following vaccination of women (n=776) with three doses of bivalent HPV vaccine (HPV-16/18) demonstrated that, over a period of up to 4.5 years, long-term vaccine efficacy was observed for HPV-16 and -18, and vaccine efficacy was also observed against incident infection with HPV-31 and -45. These findings are supported by the results of a large study (n=18,644) in women aged 15 to 25 years vaccinated with the adjuvant bivalent HPV vaccine (HPV-16/18). Over a period of 6 months, cross-protection was observed against persistent infections with HPV-45, -31 and -52, and at 12 months, modest protection was demonstrated against persistent infections with 12 combined oncogenic HPV types.