Human papillomavirus vaccines and the potential for cross-protection between related HPV types

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Abstract

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.

Section snippets

Human papillomavirus phylogenetic tree

The human papillomavirus (HPV) belongs to the papillomavirus family, within which there are different genera [1], [2]. These different genera are phylogenetically related but may be biologically diverse. The genus alpha papillomavirus is most common in humans, however, the genus beta papillomavirus can be found in a small proportion of individuals, such as those who are immunocompromised [1], [2], [3]. Closely related HPV strains have been categorized into species. At present, approximately 200

Cross-protection following natural infection with HPV

After an initial infection with HPV, subsequent infections are common [7]. However, with subsequent HPV infections, there may be a reduced risk of contracting the same strain of HPV. A US-based cohort of female students (n = 608; mean age 20 years) was monitored at 6-month intervals for a period of 3 years [7]. A total of 141 women were HPV-positive at baseline; the 24-month cumulative incidence of subsequent HPV infection was 71.6%. During follow-up, initial HPV infection was detected in a

Trial data on cross-protection with HPV vaccination

Recent studies conducted with HPV vaccines have demonstrated promising data on cross-protection against related HPV strains [9], [10], [11]. Vaccination against one HPV strain may in turn confer protection against heterologous HPV infections.

Summary

It is unclear whether natural HPV infection confers a reduced risk of subsequent infection with related HPV strains. However, there are preliminary data to indicate that vaccination against one HPV strain may, in turn, confer protection against heterologous HPV infections. Available in vitro data suggest that the quadrivalent vaccine (HPV-6/8/16/18) induces cross-neutralization antibodies against HPV-45. Clinical data have demonstrated that the bivalent HPV vaccine (HPV-16/18) induces

What type of cross-protection has been demonstrated by HPV vaccines?

Both the bivalent and quadrivalent vaccines have demonstrated cross-protection. While the bivalent vaccine offers cross-protection against HPV types 33 to 45, preliminary data from a recent pre-planned subgroup analysis of the FUTURE I and II trials, presented during the 47th Interscience Conference on Antimicrobial Agents and Chemotheraphy (ICAAC), demonstrate that the quadrivalent vaccine provides cross-protection against 10 HPV types (i.e., 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59) with a

Conflict of interest statement

KA has received grant/research support and is a consultant for Genzyme, GlaxoSmithKline, Merck, Gen Probe and Advaxis.

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