Vaccine efficacy against persistent human papillomavirus (HPV) 16/18 infection at 10 years after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre, prospective, cohort study

Abstract

Background A randomised trial designed to compare three and two doses of quadrivalent human papillomavirus (HPV) vaccine in adolescent girls in India was converted to a cohort study after suspension of HPV vaccination in trials by the Indian Government. In this Article, the revised aim of the cohort study was to compare vaccine efficacy of single dose to that of three and two doses in protecting against persistent HPV 16 and 18 infection at 10 years post vaccination. MethodsIn the randomised trial, unmarried girls aged 10-18 years were recruited from nine centres across India and randomly assigned to either two doses or three doses of the quadrivalent HPV vaccine (Gardasil [Merck Sharp & Dohme, Whitehouse Station, NJ, USA]; 0•5 mL administered intramuscularly). After suspension of recruitment and vaccination, the study became a longitudinal, prospective cohort study by default, and participants were allocated to four cohorts on the basis of the number vaccine doses received per protocol: the two-dose cohort (received vaccine on days 1 and 180 or later), three-dose cohort (days 1, 60, and 180 or later), two-dose default cohort (days 1 and 60 or later), and the single-dose default cohort. Participants were followed up yearly. Cervical specimens were collected from participants 18 months after marriage or 6 months after first childbirth, whichever was earlier, to assess incident and persistent HPV infections. Married participants were screened for cervical cancer as they reached 25 years of age. Unvaccinated women age-matched to the married vaccinated participants were recruited to serve as controls. Vaccine efficacy against persistent HPV 16 and 18 infections (the primary endpoint) was analysed for single-dose recipients and compared with that in two-dose and three-dose recipients after adjusting for imbalance in the distribution of potential confounders between the unvaccinated and vaccinated cohorts. This trial is registered with ISRCTN, ISRCTN98283094, and ClinicalTrials.gov, NCT00923702. Findings Vaccinated participants were recruited between Sept 1, 2009, and April 8, 2010 (date of vaccination suspension), and followed up over a median duration of 9•0 years (IQR 8•2-9•6). 4348 participants had three doses, 4980 had two doses (0 and 6 months), and 4949 had a single dose. Vaccine efficacy against persistent HPV 16 and 18 infection among participants evaluable for the endpoint was 95•4% (95% CI 85•0-99•9) in the single-dose default cohort (2135 women assessed), 93•1% (77•3-99•8) in the two-dose cohort (1452 women assessed), and 93•3% (77•5-99•7) in three-dose recipients (1460 women assessed).Interpretation A single dose of HPV vaccine provides similar protection against persistent infection from HPV 16 and 18, the genotypes responsible for nearly 70% of cervical cancers, to that provided by two or three doses.Funding Bill & Melinda Gates Foundation.

Human Papillomavirus Vaccine Efficacy and Effectiveness against Cancer

“…The most recent published study conducted in India showed that the vaccine efficacy against HPV 016 and 18 persistent infection was 95.4% (95% CI = 85.0% to 99.9%) in a single-dose cohort (Table 5) [5].…”

“…The 5-year survival rate for all people with cervical cancer is 66.3% [4]. Vaccines against HPV were introduced on the recommendation of the World Health Organization (WHO) and have been available since 2009, 2014, 2017, and 2019 [5]. The recommendations include that the primary target population for HPV vaccination should continue to be girls aged 9-14 years, prior to their becoming sexually active, to be administered two doses, and girls ≥ 15 years of age, including those younger than 15 years known to be immunocompromised and/or HIV-infected (regardless of whether they are receiving antiretroviral therapy), to be administered three doses.…”

Impact of one and two human papillomavirus (HPV) vaccine doses on community-level HPV prevalence in South African adolescent girls: study protocol and rationale for a pragmatic before–after design

“…11 For many LMICs, even a two-dose schedule remains beyond reach, a problem compounded by a global shortage of HPV vaccine 20 and, more recently, the COVID-19 pandemic. 21 There is growing evidence from retrospective analyses of incompletely dosed subgroups in randomised controlled trials [22][23][24] and programmes, 25 26 suggesting that a single dose is likely to generate satisfactory immune responses and, hence, protection against new HPV infections, and ultimately cervical cancer. These observations foreshadow potentially huge implementation advantages for cost-savings and coverage, particularly for LMIC settings, 27 and have informed recent suggestions by WHO for countries (in the context of supply and implementation constraints) to consider flexibility in the timing of the second dose for up to 3-5 years after the first dose.…”

Is the elimination of cervical cancer now 3 times easier? One-dose vaccine efficacy has far-reaching implications

“…In this context, recent research results look very promising, i.e. a single dose of vaccination against HPV has a similar efficacy to two and three doses [4]. These results may have far-reaching implications -primarily in a public health context, as it may enable a much faster eradication of HPV regionally and worldwide, moreover, those reluctant to get the HPV vaccine will be more likely to take just one dose, rather than three.…”