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Best PracticeOne dose of Human Papilloma Virus vaccine as a global strategy ...

One dose of Human Papilloma Virus vaccine as a global strategy to prevent cervical cancer

Even though Human Papilloma Virus (HPV) causes cancer in several epithelia, the priority purpose of HPV massive immunization is the prevention of cervical cancer in women, which accounts for 82% of all HPV-related cancers (1). The 2020 WHO Global Strategy to Accelerate the Elimination of Cervical Cancer as a Public Health Problem recommends that HPV vaccines should be included in all national immunization programs and should reach 90% of all girls by age 15 by 2030 (2). Prevention of cervical cancer is best achieved through the immunization of girls before they become sexually active. All currently licensed bivalent, quadrivalent and nonavalent HPV vaccines have excellent safety profiles and are highly efficacious.

The Costa Rica Vaccine Trial (CVT):

A phase III randomized clinical trial provided the initial data that one dose of the HPV vaccine could provide durable protection against HPV infection. Although the study design was to administer all participants three doses of HPV or control vaccine, 20% of women did not receive the three-dose regimens, mostly due to involuntary reasons unrelated to vaccination. Antibody levels after one dose, although lower than levels elicited by three doses, were 9-times higher than levels elicited by natural infection. Importantly, levels remained essentially constant over at least seven years, suggesting that the observed protection provided by a single dose might be durable (3).

KEN SHE 2vHPV and 9vHPV RCT:

The primary objectives of this randomized, multi-center, double-blind, controlled trial9 were to test the efficacy of immediate single dose nonavalent (9vHPV) or bivalent (2vHPV) HPV vaccination to prevent incident persistent HPV 16/18 infection. Results: At 18 months were: HPV 16/18 vaccine efficacy (VE) 97.5% (CI: 81.7-99.7%) for both 9vHPV and 2vHPV. For the sensitivity cohorts, VE against HPV16/18 9vHPV was 98.2% (CI: 86.6-99.7), 2vHPV 94.4% (CI:82.1-99.3) and extended sensitivity 100% VE (4). 

India IARC 4vHPV trial:

The Working Group reviewed the latest available data from this Indian cohort study which commenced in 2009 as a cluster RCT of 2 vs 3 doses quadrivalent (4vHPV) in 10–18-year-old girls with loss of randomization due to stopping of the study in April 2010 leaving 4 groups: 3-dose, 2-dose per protocol, 2- dose default (at 0, 2 months), and single-dose default groups. Results: Immunogenicity: Although the antibody titers to HPV types 16/18 induced by a single dose were inferior, a 10-year immunogenicity analysis using M9 ELISA test showed a steady plateau for HPV types 16 and 18. 95.4% of one-dose recipients were still seropositive for HPV16 as were 41.7% for HPV18. Efficacy: One-dose recipients had low rates of incident (3.1%) and persistent (0.1%) HPV 16/18 infection similar to the 2 (2.6%/0.1%) and 3 dose (2.9%/0.1%) groups. On the other hand, the unvaccinated control group (retrospectively recruited and non-randomized) had higher 16/18 infection rates (incident 9.7%, persistent 2.7%) (5).

DoRIS trial – Dose Reduction Immunobridging and Safety Study of 9vHPV and 2vHPV in Tanzanian girls:

The study included 930 girls 9-14 years in 6 arms (155 in each arm) and is the first trial of one dose in the target age group. Results: The study found that 1 dose was non-inferior to 2 or 3 doses for HPV16 seropositivity at month 24 for both 2vHPV and 9vHPV. For HPV18, the non-inferiority criterion was met for 2vHPV but not for 9vHPV (6). 

WHO-Summary of findings 1 vs 2 or 3 HPV vaccine doses:

With the above data, in addition to a systematic review (7), the key findings were that, whilst the immunogenicity of 2 or 3 doses is superior to one, high seropositivity is observed after one dose with all vaccines. The efficacy of two doses is not clearly superior to 1 and there was no difference in efficacy of 3 compared to 1 dose against 16/18 HPV infection (or cross protection against infection with 31/33/45) from the Costa Rica or India studies. More variation was seen in observational studies. Immunogenicity. There was high certainty evidence that one dose of HPV vaccine resulted in lower Geometric Mean Titers (GMTs) for HPV 16 and 18 than two or three doses and this was sustained for up to 5 years. There was high certainty evidence that one, two or three doses of HPV vaccine resulted in similarly high rates of seropositivity to HPV 16 and 18 and this was sustained for up to 11 years. HPV infections. There was low certainty evidence that one dose of HPV vaccine resulted in little to no difference in persistent HPV 16/18 infections compared with two or three doses (2).

WHO-Recommendations for HPV vaccination to prevent cervical cancer:

Current evidence suggests that a single dose has comparable efficacy and duration of protection as a 2-dose schedule and may offer program advantages, be more efficient and affordable. The large majority of cervical cancer cases in 2020 (88%) occurred in low-middle income countries, where they account for 17% of all cancers in women, compared with only 2% in high-income countries. In addition, one dose will contribute to improved coverage. From a public health perspective, the use of a single dose schedule can offer substantial benefits that outweigh the potential risk of a lower level of protection if efficacy wanes over time, although there is no current evidence of this (2).

REFERENCES

  1. de Martel C et al. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Health. 2020; 8(2): e180-e190. doi: https://doi.org/10.1016/S2214-109X(19)30488-7.
  2. World Health Organization. Weekly Epidemiological Record. Human papillomavirus vaccines: WHO position paper (2022 update). 2022; 97: 645–672.
  3. Kreimer AR, Herrero R, Sampson JN, et al. Evidence for single-dose protection by the bivalent HPV vaccine—Review of the Costa Rica HPV vaccine trial and future research studies. Vaccine 2018; 36: 4774-82. doi: 10.1016/j.vaccine.2017.12.078.
  4. Barnabas R, Brown ER, Onono MA, et al. Efficacy of single dose HPV vaccination among young African women. NEJM Evid 2022; 1: EVIDoa2100056. doi: 10.1056/EVIDoa2100056. 
  5. Basu 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: 1518-29. Doi https://doi.org/10.1016/S1470-2045(21)00453-8
  6. Baisley 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: e1485-93. doi https://doi.org/10.1016/S2214-109X(22)00306-0.
  7. Whitworth H, Gallagher KE, Howard N, et al. Efficacy and immunogenicity of a single dose of human papillomavirus vaccine compared to no vaccination or standard three and two-dose vaccination regimens: A systematic review of evidence from clinical trials. Vaccine 2020; 6: 1302-14. doi https://doi.org/10.1016/j.vaccine.2019.12.017.

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