Less than 3 doses of the HPV vaccine – Review of efficacy against virological and disease end points

Abstract

World Health Organization (WHO) recommended 2 doses of the Human Papillomavirus (HPV) vaccine for girls below 15 y on the basis of the immune-bridging studies demonstrating non-inferior immune response of 2 doses in the adolescent girls compared to 3 doses in the young adult women in whom the efficacy against disease is established. The biological nature of the antigens (virus-like particles) constituting the HPV vaccine is responsible for the vigorous antibody response that may make the third dose redundant. The protection offered by 2 doses has been demonstrated in non-randomized clinical trials to be comparable to that offered by 3 doses against incident and persistent infections of vaccine targeted HPV types. However, results emerging from the ecological and nested case-control studies embedded in the population based screening programs of different countries indicate reduced efficacy of 2 doses against virological and disease end points. Some recent studies observed the protective effect of single dose of the vaccine against incident and persistent infections of the vaccine targeted HPV types to be similar to 3 doses in spite of immunological inferiority. The sample size, duration of follow-ups and number of events were limited in these studies. Longer follow ups of the less than 3 doses cohorts in the ongoing studies as well as appropriately designed and ethically justifiable randomized studies are needed to establish the protection offered by the alternative schedules at least beyond 10 y of vaccination.

Can the prophylactic quadrivalent HPV vaccine be used as a therapeutic agent in women with CIN? A randomized trial

“…The efficacy of two and three doses for the treatment of CIN 2 was 50, and 72.2%, respectively. Although the results of some studies suggest that three doses of HPV vaccination is highly more effective than two doses in preventing of occurrence of cervical neoplasia [38], but some studies reported no significant difference between two and three doses [40,41]. In our study, we noted a big difference in efficacy with three doses of HPV vaccine versus two doses of vaccine.…”

“…Since the single dose of the HPV vaccine has not been proven to be effective [37][38][39][40], therefore, in the present study women who received just one dose of the vaccine were excluded. The efficacy of two and three doses of the HPV vaccine in the treatment of residual/recurrent CIN 1 was 38.6 and 63.1%, respectively.…”

Seropositivity to non-vaccine incorporated genotypes induced by the bivalent and quadrivalent HPV vaccines: A systematic review and meta-analysis

“…This review evaluated studies incorporating a three-dose schedule. Reduced dose arms in vaccine trials have demonstrated non-inferior seropositivity to vaccine genotypes and similar vaccine efficacy [33,34], resulting in a recommendation for a two dose schedule to be adopted worldwide [35]. However, reduced seropositivity to HPV31 has been demonstrated for less than three doses [36], which is likely to be a factor in the reduced vaccine efficacy observed against non-vaccine genotypes HPV31 and HPV45 in a post-hoc analysis of Cervarix® trial data [37].…”

Comparison of the long‐term impact and clinical outcomes of fewer doses and standard doses of human papillomavirus vaccine in the United States: A database study

“…Several prophylactic vaccines targeting various high‐risk HPV genotypes have been developed, and they include the bivalent vaccine (HPV‐16/18) approved in 2007, the quadrivalent vaccine (HPV‐16/18/6/11) approved in 2006, and, more recently, the nonavalent vaccine (HPV‐16/18/6/11/31/33/45/52/58) approved in 2014 . On the basis of efficacy and immune‐bridging trials, the quadrivalent human papillomavirus (4vHPV) vaccine was initially approved for girls and women aged 9 to 26 years with the recommendation of 3 doses . In 2014, the Strategic Advisory Group of Experts of the World Health Organization evaluated the available evidence and recommended 2 doses of the HPV vaccine for girls younger than 15 years.…”

“…10 On the basis of efficacy and immune-bridging trials, the quadrivalent human papillomavirus (4vHPV) vaccine was initially approved for girls and women aged 9 to 26 years with the recommendation of 3 doses. 11 In 2014, the Strategic Advisory Group of Experts of the World Health Organization evaluated the available evidence and recommended 2 doses of the HPV vaccine for girls younger than 15 years. In October 2016, the Centers for Disease Control and Prevention updated its guidelines and reduced the recommended dosing schedule for those initiating before the age of 15 years to 2 doses given at least 6 months apart.…”