Bivalent HPV vaccine substantially reduces cervical cancer, CIN3 rates

The risk of cervical cancer and grade 3 cervical intraepithelial neoplasia (CIN3) was substantially reduced among girls who were offered the bivalent human papillomavirus (HPV) vaccine, particularly those who were offered it at age 12–13 years, according to an observational study from England.

“We found a large reduction in cervical cancer rates in all three vaccinated cohorts and especially in those who were offered the vaccine in school year 8 (aged 12–13 years),” the authors said.

“As expected, vaccination against HPV was most effective in the cohorts vaccinated at ages 12–13 amongst whom the uptake was greatest and prior infection least likely,” said study co-author Dr Kate Soldan from the National Infection Service, Public Health England, London, UK.

“This study provides the first direct evidence of the impact of the UK HPV vaccination campaign on cervical cancer incidence, showing a large reduction in cervical cancer rates in vaccinated cohorts,” Soldan continued.

HPV immunization with a bivalent vaccine was introduced as routine vaccination for girls aged 12–13 years in September 2008 in England, UK. A catch-up programme for females aged 14–18 years was also introduced in 2008–2010.

The researchers used data from a population-based cancer registry to identify female residents aged 20–64 years who were diagnosed with cervical cancer or CIN3 between January 2006 and June 2019. A total of 27,946 cases of cervical cancer and 318,058 cases of CIN3 were diagnosed over the 13.7 million-years of follow-up in women aged 20 to <30 years.

Compared with unvaccinated women, girls who were aged 16–18 years when offered the HPV vaccine had a 34 percent reduced risk of cervical cancer. [Lancet 2021;398:2084-2092]

This relative reduction in risk was even greater among girls who were offered the vaccine at age 14–16 and 12–13 years, with a 62 and 87 percent reduced risk, respectively. In the latter group, 89 percent had received ≥1 dose of the HPV vaccine and 85 percent had received all three doses.

Similarly, compared with unvaccinated women, those who were offered the HPV vaccine at age 16–18, 14–16, and 12–13 years had relative reductions in risk of CIN3 of 39, 75, and 97 percent, respectively.

It was estimated that among vaccinated cohorts in England, there were 448 fewer than expected cases of cervical cancer and 17,235 fewer than expected cases of CIN3 by June 2019.

“This [study] represents an important step forward in cervical cancer prevention. We hope that these new results encourage uptake as the success of the vaccination programme relies not only on the efficacy of the vaccine but also the proportion of the population vaccinated,” Soldan said.

The authors acknowledged that HPV vaccine offer in this study applies to age groups and not unobserved factors such as behaviour and lifestyle. Additionally, data on individual-level efficacy or on the HPV types for each cancer case were not available. They also noted that cervical cancer incidence is low in young women such as the cohort studied here.

“The incidence of cervical cancer varies rapidly with age and is affected by screen-detected cancers, particularly on first screen,” they said. “The precise age of first screen and screening uptake changes over time. Even small alterations to cervical screening (or the reporting of cervical histology) or cancer registration could have substantial effect on trends in registered CIN3 in women in their 20s.”

“The relative reductions in cervical cancer, expected as a result of the HPV vaccination programme, support the anticipated vaccine effectiveness,” remarked Professors Maggie Cruickshank from the University of Aberdeen, Aberdeen, UK, and Mihaela Grigore from the University of Medicine and Pharmacy “Grigore T Popa” Lasi, Lasi, Romania, in a commentary. [Lancet 2021;398:2053-2055]

“The scale of the HPV vaccination effect reported by this study should also stimulate vaccination programmes in low-income 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,” they added.

“The most important issue, besides the availability of the vaccine … is the education of the population to accept the vaccination because a high rate of immunization is a key element of success,” they concluded.