HPV vaccination programmes reduce HPV infection, precancerous lesions with potential crossover and herd effects
Human papillomavirus (HPV) vaccination significantly reduces the frequency of genital HPV 16 and 18 infections and cervical intraepithelial neoplasia grade 2+ (CIN2+) in young women and shows signs of herd effects with a reduced frequency of anogenital warts in both young women and men, a recent study showed.
“[O]ur analyses show that vaccination* is producing substantial reductions in the infections that cause cervical cancer and precancerous lesions,” said study lead author Dr Mélanie Drolet from Université Laval, Québec, Canada.
For this systematic review and meta-analyses, the authors looked at 65 articles based on 40 studies conducted in 14 high-income countries with HPV vaccination programmes (>60 million individuals) that compared the frequency of genital HPV infections (23 articles), anogenital warts (29 articles), or CIN2+ (13 articles) pre- and post-vaccination.
Five to 8 years post-vaccination, there was an 83 percent reduction in the prevalence of HPV 16 and 18 among girls aged 13–19 years (relative risk [RR], 0.17, 95 percent confidence interval [CI], 0.11–0.25) and a 66 and 37 percent reduction in women aged 20–24 and 25–29 years, respectively (RR, 0.34, 95 percent CI, 0.23–0.49 and RR, 0.63, 95 percent CI, 0.41–0.97), despite low vaccination coverage in the latter group. [Lancet 2019;doi:10.1016/S0140-6736(19)30298-3]
Girls aged 13–19 years also experienced a significant reduction in HPV 31, 33, and 45 (RR, 0.46, 95 percent CI, 0.33–0.66).
The frequency of anogenital wart diagnosis reduced by 67, 54, and 31 percent in females aged 15–19, 20–24, and 25–29 years, respectively (RR, 0.33, 95 percent CI, 0.24–0.46, RR, 0.46, 95 percent CI, 0.36–0.60, and RR, 0.69, 95 percent CI, 0.53–0.89, respectively). There was also a significant reduction in anogenital warts among boys aged 15–19 years and men aged 20–24 years (RR, 0.52, 95 percent CI, 0.37–0.75 and RR, 0.68, 95 percent CI, 0.47–0.98, respectively).
Five to 9 years after vaccination, there was a 51 percent reduction in CIN2+ among screened girls aged 15–19 years (RR, 0.49, 95 percent CI, 0.42–0.58) and a 31 percent reduction among women aged 20–24 years (RR, 0.69, 95 percent CI, 0.57–0.84). Conversely, there was a 19 and 23 percent increased diagnosis of CIN2+ in screened and mostly unvaccinated women aged 25–29 and 30–39 years, respectively.
“Our study also shows greater and faster direct impact and herd effects in countries with multiple age-cohort vaccination and high [≥50 percent] vaccination coverage, compared with countries with single age-cohort vaccination or low [<50 percent] routine vaccination coverage,” said the researchers.
For example, there was a general trend towards a greater, albeit not consistently significant, decrease in HPV 16, 18, 31, 33, and 45 prevalence in studies conducted in populations with better vaccination coverage, as well as a significant decrease in anogenital warts among individuals aged 14–29 years in studies in countries with high vaccination coverage and multicohort vaccination. Similarly, a greater decrease in CIN2+ diagnosis in females aged 15–24 years was observed in countries with higher routine vaccine coverage than the country with single cohort or low vaccine coverage, the latter also having a greater increase in CIN2+ diagnosis among women aged 25–29 years.
The wide-reaching outcomes of vaccination programmes
“These reductions are a first sign that vaccination could eventually lead to the elimination of cervical cancer as a public health problem,” said Drolet. “We are now trying to determine when elimination could be achieved and which vaccination and screening programmes could help us achieve it faster,” she said.
As all the studies included were conducted in high-income countries, the researchers cautioned against generalizing the findings to lower-income countries, as well as to countries with populations that have different sexual behaviour (eg, later sexual debut). They also suggested avenues for future research including assessing the changes in HPV-related outcomes in populations not targeted for vaccination, such as in older men and women, and due to strains not included in the vaccine.
“The data … emphasize the importance of redoubling our efforts to tackle the fiscal, supply, and programmatic barriers that currently limit HPV vaccine programmes,” commented Professors Silvia de Sanjose from the University of Washington, Washington, US, and Sinead Delany-Moretlwe from the University of Witwatersrand, Johannesburg, South Africa. [Lancet 2019;doi:10.1016/S0140-6736(19)30549-5]
“[The authors] can help implementers concentrate on priority targets. Specifically, items like gender-neutral vaccination, number of age cohorts to be included, expansion to adult populations, and number of doses can be modulated on the basis of impact and sustainability,” they added.
De Sanjose and Delany-Moretlwe also called attention to the importance of focusing efforts on low- and middle-income countries which shoulder a major burden of HPV-related cancer deaths.