• Partha Basu, Sylla G Malvi, Smita Joshi, Neerja Bhatla, Richard Muwonge, Eric Lucas, Yogesh Verma, Pulikkottil O Esmy, PoliUsha Rani ReddyURRPublic Health Foundation of India, IIPH-Hyderabad, Hyderabad, India., Anand Shah, Eric Zomawia, Sharmila Pimple, Kasturi Jayant, Sanjay Hingmire, Aruna Chiwate, Uma Divate, Shachi Vashist, Gauravi Mishra, Radhika Jadhav, Maqsood Siddiqi, Subha Sankaran, Priya Ramesh Prabhu, KannanThiraviam Pillai Rameshwari AmmalTPRARajiv Gandhi Centre for Biotechnology, Poojappura, Thiruvananthapuram, Kerala, India., Rintu Varghese, Surendra S Shastri, Devasena Anantharaman, Tarik Gheit, Massimo Tommasino, Catherine Sauvaget, PillaiM RadhakrishnaMRRajiv Gandhi Centre for Biotechnology, Poojappura, Thiruvananthapuram, Kerala, India., and Rengaswamy Sankaranarayanan.
• Early Detection, Prevention and Infections Branch, International Agency for Research on Cancer, Lyon, France. Electronic address: basup@iarc.fr.
• Lancet Oncol. 2021 Nov 1; 22 (11): 151815291518-1529.

BackgroundA 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.FindingsVaccinated 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).InterpretationA 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.FundingBill & Melinda Gates Foundation.© 2021 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.

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