Single dose HPV vaccine in achieving global cervical cancer elimination
Authors: Victoire Fokom-Defo, Issimouha Dille, Joel Fokom-Domgue
Journal: The Lancet Global Health (2024)

Globally, cervical cancer remains a public health issue of increasing concern that could be addressed through the implementation of effective preventive measures such as human papillomavirus (HPV) vaccination, especially in low-income and middle-income countries (LMICs) in which fragile health systems have restrained the introduction and scaling-up of organised screening and treatment programmes. While most new cases and deaths from cervical cancer occur in LMICs, the worldwide HPV vaccine completion rate for girls aged 9–14 years (the primary target population for HPV vaccination) was only 17% in 2022.1WHOHuman Papillomavirus (HPV) vaccination coverage.https://immunizationdata.who.int/pages/coverage/hpv.html?CODE=Global&ANTIGEN=15HPV1_F&YEAR=Date: 2022Date accessed: January 6, 2024Google Scholar Since 2006, HPV vaccines have been licensed for cervical cancer prevention, initially as a three-dose regimen, and then as a two-dose regimen for individuals aged younger than 15 years. Based on emerging evidence suggesting that one dose of HPV vaccine is as effective in preventing HPV infection and cervical precancerous lesions as a multidose regimen, in 2022, WHO endorsed a single-dose HPV vaccination schedule in females aged 9–20 years.2WHOHuman papillomavirus vaccines: WHO position paper, December 2022.Wkly Epidemiol Rec. 2022; 97: 645-672Google Scholar By reducing costs and untangling logistics around vaccine delivery, a single-dose schedule could rapidly increase HPV vaccination rollout and access, particularly in LMICs for which the health and socioeconomic consequences of cervical cancer are alarmingly high. While the WHO recommendation of a single-dose regimen is supported by non-randomised observational data from two vaccine trials, one conducted in Latin America (the Costa Rica HPV Vaccine trial [CVT]) and one in Asia (the International Agency for Research on Cancer [IARC] India HPV trial),3Kreimer AR Sampson JN Porras C et al.Evaluation of durability of a single dose of the bivalent HPV vaccine: the CVT trial.J Natl Cancer Inst. 2020; 112: 1038-1046Crossref PubMed Scopus (77) Google Scholar, 4Basu P Malvi SG Joshi S et al.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.Lancet Oncol. 2021; 22: 1518-1529Summary Full Text Full Text PDF PubMed Scopus (80) Google Scholar the strongest and most compelling evidence comes from two ongoing vaccine trials in Africa (the Kenya single-dose HPV-vaccine efficacy [KEN SHE] trial focused on HPV infection prevention in sexually-active young women aged 15–20 years in Kenya and the Dose Reduction Immunobridging and Safety Study [DoRIS] trial focused on vaccine-mediated immune responses [seroconversion and antibody titres] in girls aged 9–14 years in Tanzania).5Barnabas RV Brown ER Onono MA et al.Efficacy of single-dose HPV vaccination among young African women.NEJM Evid. 2022; 1EVIDoa2100056 Crossref PubMed Google Scholar, 6Watson-Jones D Changalucha J Whitworth H et al.Immunogenicity and safety of one-dose human papillomavirus vaccine compared with two or three doses in Tanzanian girls (DoRIS): an open-label, randomised, non-inferiority trial.Lancet Glob Health. 2022; 10: e1473-e1484Summary Full Text Full Text PDF PubMed Scopus (18) Google Scholar In the Lancet Global Health, Kathy Baisley and colleagues compared HPV 16 and HPV 18 antibody responses after one dose of HPV vaccine (Cervarix or Gardasil-9) in the DoRIS trial with those in the KEN SHE trial.7Baisley K Kemp TJ Mugo NR et al.Comparing one dose of HPV vaccine in girls aged 9–14 years in Tanzania (DoRIS) with one dose in young women aged 15–20 years in Kenya (KEN SHE): an immunobridging analysis of randomised controlled trials.Lancet Glob Health. 2024; 12: e491-e499Google Scholar In this immunobridging analysis, the immune responses 24 months after receiving a single dose of Cervarix or Gardasil-9 in girls aged 9–14 years was found to be non-inferior to those in young women aged 15–20 years from the KEN SHE trial who were randomised to a single dose of the same vaccines and in whom efficacy had been shown up to 36 months following vaccine administration. This study complements and strengthens findings from a previous DoRIS trial report, which showed that antibody levels among girls receiving one dose of Gardasil-9 or Cervarix were at least as high as those in women from two historical cohorts (from the CVT or IARC India HPV trials).8Baisley K Kemp TJ Kreimer AR et al.Comparing one dose of HPV vaccine in girls aged 9–14 years in Tanzania (DoRIS) with one dose of HPV vaccine in historical cohorts: an immunobridging analysis of a randomised controlled trial.Lancet Glob Health. 2022; 10: e1485-e1493Summary Full Text Full Text PDF PubMed Scopus (20) Google Scholar While data from these two historical cohorts have shown that protection against HPV infection and cervical precancerous lesions from a one-dose vaccine regimen is durable and can last for at least a decade,3Kreimer AR Sampson JN Porras C et al.Evaluation of durability of a single dose of the bivalent HPV vaccine: the CVT trial.J Natl Cancer Inst. 2020; 112: 1038-1046Crossref PubMed Scopus (77) Google Scholar, 4Basu P Malvi SG Joshi S et al.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.Lancet Oncol. 2021; 22: 1518-1529Summary Full Text Full Text PDF PubMed Scopus (80) Google Scholar this long-lasting protection is yet to be confirmed in the ongoing cohorts from the KEN SHE and DoRIS trials. The recent findings from Baisley and colleagues, suggest that the efficacy of a single dose of HPV vaccine could apply to malaria endemic areas and settings in which other conditions interfering with immunity, such as lymphatic filariasis and intestinal parasitosis, are highly prevalent. Although the 9-valent vaccine—that provides wider protection against cervical cancer than the 2-valent vaccine—was used in the two trials (KEN SHE and DoRIS) considered in this study, the authors limited their immunobridging analysis to HPV types 16 and 18, and did not examine immune responses to the other five oncogenic HPV types (31, 33, 45, 52, and 58) targeted by the 9-valent vaccine, or to the oncogenic HPV types not genetically related to those targeted by 2-valent and 9-valent vaccines. Considering more HPV types might have given better insights into the dynamics of HPV infection and the possible shifts in the epidemiology and natural history of HPV among vaccinated girls and women in high-burden settings. Assessment of cross-protection (ie, a decrease in the prevalence of HPV types genetically related to vaccine-types due to the polyclonal immune response to vaccination) and type replacement (ie, an increase in the prevalence of HPV non-vaccine-types to occupy the ecological niche vacated by the decrease in the prevalence of HPV vaccine-types) after HPV vaccine introduction are crucial to inform vaccination recommendations and guide health policies. Performing these additional analysis not only would have helped examine the cross-protective efficacy of Gardasil-9 against non-vaccine types, but also, would have helped confirm that cross-protection of Cervarix against other oncogenic types than 16 and 18 that has been observed in previous clinical trials,9Wheeler CM Castellsagué X Garland SM et al.Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic HPV types: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial.Lancet Oncol. 2012; 13: 100-110Summary Full Text Full Text PDF PubMed Scopus (416) Google Scholar is also seen in African populations. Such data might have provided further evidence to policy makers and funding agencies, and contributed to advocating for the introduction of the 9-valent HPV vaccine in LMICs, in which the 2-valent (Cervarix) and the 4-valent (Gardasil) vaccines are the only vaccines available through national immunisation programmes. This is particularly important for African, Caribbean, and Pacific countries, because certain oncogenic HPV types not targeted by the 2-valent and 4-valent vaccines were found to be highly linked with cervical carcinogenesis in Black women.10Pinheiro M Gage JC Clifford GM et al.Association of HPV35 with cervical carcinogenesis among women of African ancestry: evidence of viral-host interaction with implications for disease intervention.Int J Cancer. 2020; 147: 2677-2686Crossref PubMed Scopus (39) Google Scholar Future studies focusing on younger age groups (ie, children younger than 9 years) and on settings with different HPV epidemiological profiles including areas with high HIV prevalence will help generate stronger evidence on the effectiveness of a one-dose HPV vaccination regimen in sociodemographically, geoclimatically, and epigenetically diverse populations. Despite the need for clinical trial data to support the long-term immune response of a single-dose HPV vaccination regimen (which are expected to arise from the continued monitoring of girls and women enrolled in the KEN SHE and DoRIS trials), this study contributes to the growing body of evidence challenging the widely admitted paradigm that protein-based subunit vaccines require a multidose regimen to yield a long-lasting and adequate immune response. We declare no competing interests. Comparing one dose of HPV vaccine in girls aged 9–14 years in Tanzania (DoRIS) with one dose in young women aged 15–20 years in Kenya (KEN SHE): an immunobridging analysis of randomised controlled trialsHPV16 and HPV18 immune responses in young girls 24 months after a single dose of 2-valent or 9-valent HPV vaccine were comparable to those in young women who were randomly assigned to a single dose of the same vaccines and in whom efficacy had been shown. A single dose of HPV vaccine, when given to girls in the target age range for vaccination, induces immune responses that could be effective against persistent HPV16 and HPV18 infection at least two years after vaccination. Full-Text PDF Open Access