9-valent HPV vaccine offers sustained immunogenicity, effectiveness and tolerability for over a decade in adolescent populations

27 Sep 2023

The noninferior immunogenic responses of the 9-valent human papillomavirus (9vHPV) vaccine among adolescents boys compared with adolescent girls observed in Study V503-002 hinted at the vaccine’s potential efficacy in preventing HPV infections and related diseases for young man as well.1 An extension of this study reported remarkable long-term efficacy and safety profile of the 9vHPV vaccine through 10 years of after vaccine administration.2 These findings further implied a desirable risk-benefit profile of the 9vHPV vaccine.2

Compared to the quadrivalent HPV (qHPV) vaccine, which only protects against 4 serotypes of HPV-6, 11, 16 and 18, the 9vHPV vaccine covers 5 added serotypes including HPV-31, 33, 45, 52, and 58, granting additional HPV prevention.3 A pivotal study, V503-001, revealed that among women aged 16-26 years, a 3-dose regimen of the 9vHPV vaccine could reduce the incidence of high-grade cervical disease and cervical sur gery related to the 9 targeted HPV types by 98.2% (95% CI: 93.6-99.7%) and 97.8% (95% CI: 93.4-99.4%) respectively  for up to 4 years.3 Similarly, the 3-dose regimen of 9vHPV vaccine in Study V503-002 had exhibited noninferiority in antibody response  among adolescents of both genders aged between 9 to 15 compared to young women only. It has achieved an overall seropositive rate of >99% for each vaccine-targeted HPV serotype within 7 months of administrating the first dose.1 An extension of this study was conducted to monitor the longevity of the 9vHPV vaccine’s effectiveness and safety among the adolescent population 10 years after vaccination.2

This extension study was conducted from 2009 to 2021, enrolling a total of 1,272 adolescent participants (76.3% female) who received 3 doses of the 9vHPV vaccine between the ages of 9 and 15.2 Throughout the study period, 350 participants discontinued due to voluntary withdrawal or being lost to follow-up, resulting in a 72.5% completion rate in the initial population.2

The primary endpoints consisted of changes in the participants’ geometric mean titer (GMT) of antibodies against the 9 HPV serotypes throughout the study period, quantified by the 9-valent competitive Luminex immunoassay (cLIA) and the HPV-9 Immunoglobulin  G Luminex immunoassay (IgG-LIA).2 The secondary endpoint of the study was the composite incidence of persistent infection (≥6 months in duration ± 1 month of visit window) and diseases related to the  9 vaccine-targeted HPV subtypes.2 Incidence of cervical intraepithelial neoplasia (CIN), adenocarcinoma in situ (AIS), vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), genital warts (i.e., condyloma acuminatum), cervical, vaginal, and vulvar cancer were evaluated for female participants.2 For male participants, the incidence of penile intraepithelial neoplasia (PIN), genital warts, penile, perineal and perianal cancers were recorded.2 Additionally, the incidence of vaccine-related serious adverse events (SAEs) was evaluated as the safety endpoint for this study.2

The 9vHPV vaccine exhibited sustained immunogenic benefits for adolescents in this follow-up study.2 Overall, results obtained with the cLIA indicated a seropositive rate of 81.3% to 97.7% during month 126, while the more sensitive IgG-LIA concluded a seropositive rate of 94.9 to 100% at month 126.2 Across the antibodies against each HPV serotype, cLIA-assessed and  IgG-LIA-assessed GMTs peaked at 7-months post-vaccination.2 The GMTs for all serotypes dwindled at an accelerated rate  between months 7 to 12, then resumed a gradual decrease through month 126.2 The GMTs of anti-HPV were analogous between the male and female cohorts in each timepoint throughout the study.2 It was noted that a numerically higher anti-HPV GMTs were associated with participants who received the 9vHPV vaccine at a younger age of 9 to 12 when compared to those who received the 9vHPV vaccine at ages 13 to 15.2

The findings of this study also indicated the retention of 9vHPV vaccine’s effectiveness after a decade.2 Among the female participants, the composite incidence of 6-month persistent infection and diseases related to vaccine-targeted HPV subtypes were 52.4 per 10,000 person-years and 2.2 per 10,000 person-years respectively.2 No cases of high-grade CIN and VIN or VaIN related to  vaccine-targeted HPV subtypes were recorded.2 For male participants, the composite incidence of 6-month persistent infection and diseases related to vaccine-targeted HPV subtypes were 54.6 per 10,000  person-years and 0 per 10,000 person-years respectively.2 No cases of disease were associated with vaccine-targeted HPV subtypes.2 All in all, the incidence rates of persistent infection and disease in this extension study were comparable to that of vaccinated cohorts in previous epidemiologic studies of the 9vHPV and qHPV vaccines.2 In terms of safety, no vaccine-related SAEs or deaths were recorded throughout the study period, reaffirming the long-term tolerability of the 9vHPV vaccine.2

In summary, this extension study revealed that the immunogenicity, effectiveness, and tolerability of the 9vHPV vaccination among adolescents aged 9 to 15 years could be sustained over a decade.2 The reported safety in this study was also consistent with prior HPV vaccination studies.2

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