Vaccine effectiveness against HPV infections

Infections with human papilloma viruses (HPV) are the most prevalent sexually transmitted diseases. The vast majority of the sexually active population acquires them during lifetime but almost all HPV infections become resolved within a year. A small fraction of infections persists and can lead to cervical lesions, which may progress to cancer and their appearance is controlled by long-established cervical screening programs. Since licensure of the first HPV vaccines almost 15 years ago, more than one hundred countries introduced HPV vaccination into their national immunization strategies in order to prevent cervical cancer development. Despite permanent evaluation of immunological, virological and clinical endpoints of vaccine effectiveness, the antibody dynamics and protection are not fully understood, which is particularly true after natural infection. We thus studied humoral immune responses after natural infection and vaccination. In addition, we investigated reasons for rare events of cervical lesion development after immunization. In studies of serological responses to HPV infections (papers I and II) we demonstrated that the characteristics of type-specific anti-HPV antibodies to the most common oncogenic types (HPV 16 and 18) apply also to the other high-risk HPVs. Serum antibodies were generally stable over time and were strongly associated with cervical HPV DNA positivity. Seropositivity to multiple anogenital HPV types was also associated with presence of HPV DNA and we observed an association with an abnormal cytology and with the presence of non-genital HPVs. The latter finding suggests that a definite subset of women is more likely to seroconvert to multiple HPV types, which could be true also in induction of antibody responses to HPV vaccines. Our serology assay was validated using HPV DNA from serially collected cervical samples as a standard. This was shown to be a valuable approach for evaluation of assay performance since repeated sampling for tr