Long-term efficacy and safety of human papillomavirus vaccination

Abstract

In this paper, we review the published evidence about the long-term efficacy of the available human papillomavirus (HPV) vaccines and their safety profile. Two prophylactic HPV vaccines – bivalent (bHPV) and quadrivalent (qHPV) – are now available, and vaccination programs are being widely implemented, primarily targeting adolescent girls. Efficacy has been widely demonstrated for both vaccines. Since the risk of HPV exposure potentially persists throughout a woman’s sexual life, vaccine duration of protection is critical to overall effectiveness. Interpreting the results of long-term efficacy studies for the two HPV vaccines can be puzzling, due to the heterogeneity of studies, different methods used in the assessment of immunogenicity, histopathological and virological end points, and statistical power issues. Moreover, an immunologic correlate of protection has not yet been established, and it is unknown whether higher antibody levels will really result in a longer duration of protection. Disease prevention remains the most important measure of long-term duration of vaccine efficacy. To date, the longest follow-up of an HPV vaccine has been 9.4 years for the bHPV vaccine. Long-term follow-up for qHPV vaccine goes up to 8 years. The vaccine continues to be immunogenic and well tolerated up to 9 years following vaccination. All randomized controlled clinical trials of the bHPV and the qHPV vaccines provide evidence of an excellent safety profile. The most common complaint reported is pain in the injection site, which is self-limiting and spontaneously resolved. The incidence of systemic adverse events (AEs), serious AEs, and discontinuations due to a serious AE reported in clinical studies are similar between the two vaccines and their control groups. In particular, no increased risk of autoimmune disease has been shown among HPV-vaccinated subjects in long-term observation studies. As these are crucial topics in HPV vaccination, it is important to establish systems for continued monitoring of vaccine immunogenicity, efficacy, and safety over time.

Immunological effects of adjuvants, their mechanisms, and relevance to vaccine safety

“…Adjuvants are generally considered principally responsible for the usual mild to moderate vaccine reactions (redness and swelling at the injection site, low-grade fever, fatigue, myalgia, headache), since these reactions are mostly caused by the activation of innate immunity, with brief release of inflammatory mediators. More serious adverse reactions to adjuvants have been repeatedly found to be rare (30,31,41,42). However, some adjuvants have tentatively been linked to pathological conditions.…”

Eficácia das Vacinas Contra o Vírus do Papiloma Humano nas Mulheres com mais de 24 Anos na Prevenção do Cancro do Colo do Útero

“…4 Entre os anos 2000 e 2013 morreram mais de 200 mulheres por ano devido ao CCU (cerca de três em cada 100 000 mulheres), 5 no entanto, este valor poderá representar uma subestimativa, uma vez que alguns casos de CCU são classificados como "tumor maligno do útero, porção não especificada" e não são contabilizados nesta estatística. 5 A infeção pelo HPV é condição necessária na quase totalidade dos casos de CCU, [5][6][7][8][9][10] existindo mais de 100 genótipos do HPV estudados; 90% dos casos de CCU são provocados pelos genótipos de alto risco (oncogénicos) 16,18,45,31,33,52, 58 e 35. 5,[10][11][12][13][14] A infeção pelos genótipos 16 e 18 está na origem da grande maioria dos casos de CCU Revista Científica da Ordem dos Médicos www.actamedicaportuguesa.com Ribeiro JP, et al Eficácia das vacinas contra o HPV nas mulheres com mais de 24 anos na prevenção do CCU, Acta Med Port 2016 Jun;29 (6): [401][402][403][404][405][406][407][408] -mais de 70% dos casos, 5,6,10,[14][15][16][17] enquanto aproximadamente 10% são consequência da infeção pelos genótipos 45 e 31, 15 e os restantes são causados por outros genóti-pos oncogénicos.…”

“…18,19 A maioria das infeções por HPV é transitória, 6,15 ocorrendo resolução espontânea em 90% dos casos após dois anos, 15 que, no entanto, não confere imunidade contra a infeção pelo vírus. 6,9,12,13,15,16 A eficácia das vacinas contra o HPV nas mulheres até aos 25 anos de idade está bem comprovada, 10,11,16,17,19 porém, a eficácia em idades superiores ainda não está totalmente estabelecida e existem dúvidas quanto à sua utilização.…”

“…6,14,15 A segurança e tolerabilidade das vacinas foi avaliada em vários estudos, apresentando perfis semelhantes nos grupos vacinados e controlo, e foram consideradas vacinas com alto perfil de segurança, 6,9,12,15,16,20,23 é ainda necessário comprovar este facto para a vacina nonavalente, devido à sua recente aprovação e à existência de poucos estudos.…”

Long-term modeling on HPV vaccination: do we really need any more?

“…Both protect against initial infection with HPV types 16 and 18, the most frequently associated with CC; the quadrivalent vaccine against types 6 and 11 too, which cause 90% of genital warts [2]. Although the longest follow-up is only approximately 10 years so far [3], the two vaccines have proved effective. The manufacturers launched the two vaccines at three-dose schedules and very high prices worldwide.…”