The human papillomavirus (HPV) infection is the most common sexually transmitted disease in the world. Most sexually active individuals of both sexes will acquire an HPV infection at some point in their lives. Although most HPV infections clear within two years, approximately 10% persist, possibly resulting in the development of precancerous lesions and cancer.
The most common high-risk (hr) HPV types 16 and 18 cause up to 70% of cervical cancers, and all hrHPVs are responsible for 5% and 10% of all cancers worldwide in males and females, respectively. HrHPVs cause up to 100% of cancers in the cervix, 90% in the anus, 35-50% in the oropharynx, 50% in the vulva, 64-91% in the vagina and 40-45% in the penis. Decreasing the transmission of prevalent undetected, asymptomatic, and long-term HPV infections by vaccination is therefore of utmost interest. The licensed vaccines - the bivalent vaccine comprising HPV types 16 and 18 and the quadrivalent vaccine comprising HPV types 6, 11, 16 and 18 are safe and 90-100% efficacious against persistent infections and precancerous cervical lesions associated with HPV types 16 and 18. Both vaccines have also shown 97-100% efficacy against cervical intraepithelial neoplasia (CIN) 2+, CIN3, and adenocarcinoma in situ (AIS) associated with the vaccine types. Both vaccines protect against anogenital infections with the non-vaccine HPV type 31, and the bivalent vaccine additionally against the non-vaccine types 33, 45 and 51. Some vaccine efficacy against oropharyngeal infection has been shown for the bivalent vaccine and against anal HPV infection for both vaccines.
The purpose of this thesis is to evaluate the antibody responses following HPV 16/18-vaccination in adolescent girls and boys and young women and men. The antibody responses up to four years following the HPV 16/18 vaccination were evaluated in adolescent girls and young women. Also, antibody levels of HPV 16/18 in serum samples and cervical secretions were compared in young women. The prevalence of HPV deoxyribonucleic acid (DNA) was compared in HPV 16/18-vaccinated and non-vaccinated young men. The University of Tampere, School of Health Sciences, conducted these prospective clinical studies in collaboration with GlaxoSmithKline at several study sites in Finland and abroad during 2004-2013. The immune responses in adolescent girls and boys aged 10-14, and young women and men aged 15 to 25, were excellent, with approximately 100- and 40-fold (HPV 16 and 18) higher antibody titers as compared to those resulting from natural HPV infections. The antibody titers were higher in younger age groups of both genders than in young women. Sustainability of the high antibody levels following vaccination with the HPV 16/18 vaccine was demonstrated in adolescent girls and young women up to four years. The level of mucosal antibodies correlated with the serum antibody levels in young women four years post vaccination. HPV 16/18 antibodies, transudated through the epithelium to mucosal surfaces, provide protection at sites where infection occurs. Vaccination also reduced the prevalence of vaccine HPV types HPV 16 and 18 in males, ensuring reduced transmissibility. High antibody levels will most likely persist for a long time. As HPV infections are usually acquired within three years of sexual debut, the HPV vaccination should be administered prior to this to both girls and boys, to achieve the desired herd immunity with a reduction in the global HPV burden.