England’s human papillomavirus (HPV) vaccination program has nearly eliminated cervical cancer in young women, with rates of cervical cancer and grade 3 cervical intraepithelial neoplasia (CIN3) dropping by 87% and 97%, respectively, for girls born since Sept. 1, 1995, researchers found.
The HPV immunization program in England first rolled out on Sept. 1, 2008, with the goal of preventing persistent infections from HPV types 16 and 18, which are responsible for around 80% of all cervical cancers in the U.K., Peter Sasieni, PhD, of Guy’s Cancer Center at Guy’s Hospital in Great Maze Pond, London, and colleagues explained in The Lancet.
Routine three-dose vaccinations with a bivalent vaccine (Cervarix) were offered to girls ages 12-13 years (school year 8 in the U.K.), and catch-up services were available for girls ages 14-18 years. As a result, annual three-dose HPV vaccine coverage in the U.K. from 2008-2012 was quite high for girls ages 12-13 (range 80.9-88.0%) but lower for the older age groups (70.8-75.7% for ages 14-16; 38.9-48.1% for ages 16-18).
Early models suggested that HPV vaccination would not make a dent in cervical cancer rates for at least eight years after vaccination but that the program would substantially reduce cervical cancer incidence among women ages 20-29 years by the end of 2019.
Now, over 10 years after the start of England’s HPV vaccination program, Sasieni and colleagues used population-based cancer registry data to estimate the early impact of the bivalent vaccine on cervical cancer and CIN3.
For their observational analysis, the study authors defined three vaccinated cohorts in order to account for the school year in which the vaccine was offered (ages 12-13, 14-16, or 16-18) and differences in vaccination coverage between these groups. They also included four unvaccinated cohorts based on date of birth and divided these “so as to distinguish between groups of women who would have been offered cervical screening from different ages,” they explained. “The most recent unvaccinated cohort (born between May 1, 1989 and Aug. 31, 1990) served as the comparator for the other cohorts.”
The study authors noted that—using a lower limit of expected effectiveness by assuming that any fewer than three HPV vaccine doses provides no protection and an upper limit by assuming 100% efficacy from a single dose—the HPV vaccine was expected to induce a cervical cancer risk reduction of 36-48%, 59-64%, and 68-71% for those offered vaccination at ages 16-18, 14-16, and 12-13 years, respectively.
Data for cervical cancers diagnosed from Jan. 1, 2006 through June 30, 2019, among women ages 20-64 years residing in England were extracted from the dataset produced by the National Cancer Registration and Analysis Service of Public Health England. The final analysis consisted of 13.7 million-years of follow-up from women ages 20 to <30 years.
“The estimated relative reduction in cervical cancer rates by age at vaccine offer were 34% (95% CI 25–41) for age 16-18 years (school year 12-13), 62% (52-71) for age 14-16 years (school year 10-11), and 87% (72-94) for age 12-13 years (school year 8), compared with the reference unvaccinated cohort,” Sasieni and colleagues found. “The corresponding risk reductions for CIN3 were 39% (95% CI 36-41) for those offered at age 16-18 years, 75% (72-77) for age 14–16 years, and 97% (96-98) for age 12-13 years. These results remained similar across models. We estimated that by June 30, 2019 there had been 448 (339-556) fewer than expected cervical cancers and 17,235 (15,919-18,552) fewer than expected cases of CIN3 in vaccinated cohorts in England.”
The study authors pointed out that the expected risk reductions for cervical cancer among the ages 16-18 and 14-16 years cohorts under the scenario requiring three doses and assuming no cross-protection or herd immunity (36% and 59%, respectively) fell well within the 95% CIs for both groups; however, “the magnitude of the reduction reported for individuals offered the vaccine in school year 8 (87% for cancer and 97% for CIN3) was much greater than would be expected (68%) under that scenario and also than would be expected assuming a single dose provides 100% protection against HPV 16 and 18 (71%).”
One possible explanation for this larger-than-expected risk reduction could be that HPV prevalence was particularly high in the U.K., with a study by Mesher and colleagues demonstrating that the prevalence of HPV 16/18 in the U.K. was as high as 92.9% (95% CI 85.6-97.0) among women diagnosed with cervical cancer before age 30 years. Another possibility is that unvaccinated women may have benefited from herd protection, or that the vaccine offered cross-protection against HPV infections other than types 16 and 18, “as shown for high-grade disease and type-specific HPV infection.”
“Regardless of the explanation, our findings should greatly reassure those still hesitant about the benefits of HPV vaccination,” Sasieni and colleagues concluded. “We have shown that HPV vaccination with high coverage in 12–13 year old girls has almost eliminated cervical cancer and cervical precancer up to age 25 (the extent of the observed data).”
However, as Maggie E. Cruickshank, of the University of Aberdeen in Aberdeen, U.K., and Mihaela Grigore, of the University of Medicine and Pharmacy “Grigore T. Popa” Lasi in Romania, pointed out in a commentary accompanying the study that those benefits will only take hold if vaccine uptake is increased, not just in England but around the globe.
“The relative reductions in cervical cancer, expected as a result of the HPV vaccination program, support the anticipated vaccine effectiveness,” Cruickshank and Grigore wrote. “Yet, even in a wealthy country, such as England with free access to HPV immunization, uptake has not reached the 90% vaccination target of girls aged 15 years set by WHO. Covid-19 is an additional challenge to delivering HPV vaccination but only adds to a long list, including access to affordable vaccines, infrastructure for low temperature-controlled supply chains, delivery, and waste disposal.”
Importantly, Cruickshank and Grigore argued that the findings by Sasieni et al should be used to bolster HPV vaccination programs in low- and middle-income countries, “where the problem of cervical cancer is a far greater public health issue than in those with well established systems of vaccination and screening.” In countries such as these, apart from increasing the availability of shots, there is a crucial need to educate the population to accept those vaccines, “because a high rate of immunization is a key element of success,” they added.
“Girls and women eligible for HPV vaccination should be encouraged to receive the vaccine, at any age but ideally when first offered it, to ensure that this hugely successful vaccination program continues to benefit younger generations,” Sasieni and colleagues concluded.
Study limitations included that individual-level data on vaccination status and HPV type associated with individual cervical cancer cases was not available; and the “relatively small numbers of individuals with cancers expected (in the absence of vaccination) in the vaccinated cohorts,” the study authors noted.
- The U.K. human papillomavirus (HPV) vaccination campaign, started in 2008, has led to relative risk reductions of 87% and 97% for cervical cancer and grade 3 cervical intraepithelial neoplasia (CIN3), respectively, in girls who received their shots at ages 12-13.
- Note that while the relative risk reductions in cervical cancer risk support the efficacy of the HPV vaccine, England has not reached the WHO’s recommended 90% vaccine coverage target for girls at age 15, suggesting a need to increase vaccine uptake.
John McKenna, Associate Editor, BreakingMED™
The study authors and editorialists had no relevant relationships to disclose.
Cat ID: 120
Topic ID: 78,120,730,120,935,28,178,138,44,192,561,151,925
