Treatment, Follow-up, and Prevention of Papillomavirus Infection and Cervical Cancer

Abstract

Human Papillomavirus (HPV) infection is the main factor associated with the development of cervical cancer. The majority of 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-6/11/16/18) show neutralization of HPV-45 pseudovirions. Cross-protection following vaccination of women with three doses of bivalent HPV vaccine (HPV-16/18) demonstrated that long-term vaccine efficacy was observed for HPV-16 and HPV-18, and vaccine efficacy was also observed against incident infection with HPV-31 and HPV-45. These findings are supported by the results of a large study in women aged 15–25 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, HPV-31, and HPV-52, and at 12 months, modest protection was demonstrated against persistent infections with 12 combined oncogenic HPV types (Ault KA (2007a) Human papillomavirus vaccines and the potential for cross-protection between related HPV types. Gynecol Oncol 107:S31–S33). Anyway, the currently available HPV vaccines can prevent infection by certain HPV types, but not all. At present, research efforts are being devoted to developing more broad-spectrum preventative vaccines, as well as therapeutic vaccines. In the future, the use of mosaic virus-like particles (VLP), comprising at least one late (L1) protein of each HPV type, may be able to prevent infection by all HPV types while patented codon-optimization techniques and the use of edible or deoxy-ribonucleic (DNA)-based vaccines may be good places to start for reducing costs. Future vaccines should ideally have both preventive and therapeutic efficacies. Enhanced immunogenicity could be achieved by the use of more effective adjuvants, such as nanoparticle-based delivery systems, or new classes of adjuvants (Cho HJ, Oh YK, Kim YB (2011) Advances in human papilloma virus vaccines: a patent review. Expert Opin Ther Pat 21:295–309).