Study Finds 90% Drop in Cervical HPV Infections Among Vaccinated U.S. Females

Human papillomavirus (HPV) vaccines were linked with a 90% impact in reducing cervical, vaccine-type infections in girls and young women who actually got the vaccine, researchers reported.

In a cross-sectional study, the impact of the quadrivalent HPV vaccine (4vHPV) on 4vHPV-type prevalence (HPV 6, 11, 16, and 18) in 2015 to 2018 was 85% among sexually experienced females (ages 14 to 24 years) and 74% among unvaccinated females, according to Hannah G. Rosenblum, MD, of the CDC in Atlanta, and co-authors.

They also noted in the Annals of Internal Medicine that there were no significant declines found in non-4vHPV-type prevalence and that the vaccine effectiveness ranged from 60% to 84% during vaccine eras for females, while it came in at 51% during 2013 to 2016 for males.

"Twelve years into the United States’ HPV vaccination program, national data demonstrate an increasing impact among females, strong herd effects among unvaccinated females in the context of increasing HPV vaccination coverage among both males and females, and greater percentages of persons receiving the HPV vaccine in early adolescence before HPV exposure through sexual contact," Rosenblum’s group concluded.

Their findings, based on an analysis of National Health and Nutrition Examination Survey (NHANES) pre-vaccine and in the vaccine era, are "consistent with other sources," such as a 2016 meta-analysis, that "also suggest[ed] substantial reductions in vaccine-type HPV infections and precancer among vaccinated populations," according to Rebecca Perkins, MD, MSc, of Boston University School of Medicine, and co-authors.

They noted in an editorial accompanying the study that data from a 2020 population-based study in Sweden "indicate near elimination of cervical cancer diagnosed before age 30 among women who received on-time vaccination."

But Perkins’ group also pointed out that the pandemic did not do HPV vaccination rates any favors, reversing "much of the progress made in recent years… During the pandemic, providers and health systems have deprioritized adolescent vaccination, and particularly HPV vaccination, which in turn has led to more severe drops for HPV vaccination than for other adolescent vaccinations, and for adolescent vaccination compared with early childhood and adult vaccinations." It could "take a decade to recover" from this "shortfall," they cautioned.

In an American College of Physicians interview, Rosenblum also stressed that, despite the "good news" from the study, "we know there have been vaccination program disruptions during the Covid-19 pandemic. Since this could threaten strides made in the previous decade, all efforts are needed to ensure that children and adolescents receive routinely recommended vaccinations."

Perkins and co-authors called for healthcare providers to talk up the HPV vaccine with the patients; that nurses should be allowed to provide the vaccine without interaction with a physician; and that reminder programs could revive the vaccination effort. The authors of a 2021 JAMA research letter outlined other "[p]ossible strategies to improve vaccination uptake and completion among young adults [including] leveraging university or community vaccination campaigns… identification of the need for HPV vaccination at the time of influenza vaccination, elimination of cost barriers, and improved education of adult primary care clinicians regarding the risk of HPV-associated cancers."

"As we aim to rebuild health care services in the post-pandemic era, we have over a decade of research on how to effectively provide HPV vaccinations to children and adolescents in the United States," they added.

The health community began advising receipt of the quadrivalent HPV vaccine for females in 2006, and for males five years later. In 2015, the nine-valent vaccine (Gardasil 9) came on the market.

The Advisory Committee on Immunization Practices’ guidelines from 2014 support vaccination for males (ages 13 to 21 years), catch-up vaccination through age 26 years for all women, men who have sex with men, transgender persons, and immunocompromised persons up to age 26 years. A 2020 update advised that "[c]linicians should use shared decision-making to offer [HPV] vaccination to adults aged 27 to 45 years who have not started or completed the vaccine series based on individual risk factors and likelihood of benefit."

Data for the current study came from participants, ages 14 to 24 years, who were sexually experienced. The authors noted that, in the U.S. in 2015 to 2018, almost 50% of children received their first vaccination before age 15 years versus 18.6% for boys and 27.2% for girls in 2011 to 2014.

Rosenblum’s group reported that since vaccination was introduced, female and male vaccination rates increased to 59% and 29.5%, respectively, in 2015 to 2018. But they also found that vaccine effectiveness in females seemed to drop from 84% in 2011 to 2014 to 60% in 2015 to 2018. From 2013 to 2016, vaccine effectiveness was around 51% for men.

They warned that vaccine effectiveness can be a misleading metric. "As herd protection increases and prevalence among unvaccinated persons decreases, vaccine effectiveness might be difficult to estimate," the authors said. "We do not believe that these findings raise concerns about waning immunity; multiple studies show long-lasting protection after HPV vaccination."

Study limitations included self or parent-reported vaccination history and the fact that the majority of data came from White participants.

Based on related research, it would seem individual states are putting in a lukewarm effort to promote HPV vaccination. For instance, a 2019 cross-sectional analysis of HPV vaccine statutes and regulations, found "continued state reluctance to develop a policy to expand HPV vaccination," despite a big push from Merck (developer of Gardasil) and Women in Government. A 2021 KFF report noted that Hawaii, Rhode Island, Virginia, and Washington D.C. have laws that require HPV vaccination for school entry, but in some cases, parents are allowed to opt out due to "medical, moral, or religious opposition."

And a 2020 study in Puerto Rico found that a pair of "focusing events" — the 2015 death from cervical cancer of Rhaiza Vélez Plumey at age 32 and the release of the VOCES HPV Advisory Panel Report — hastened the adoption process of the HPV vaccine school-entry requirement in the U.S. territory, but that access and cost were still barriers.

The HPV vaccination push seems to be going better on a national level: In 2014, the CDC and the American Cancer Society (ACS) joined up to create the HPV VACs Project (headed up by editorial co-author Debbie Saslow, PhD, of ACS), which administers the HPV Vaccination Initiative Contact Map and the Resource Clearinghouse.

The study was supported by the CDC.

Rosenblum, Perkins, Saslow, and co-authors, reported no relationships relevant to the contents of this paper to disclose.

Rosenblum HG, et al "Human papillomavirus vaccine impact and effectiveness through 12 years after vaccine introduction in the United States, 2003 to 2018" Ann Intern Med 2022; DOI: 10.7326/M21-3798.

Perkins RB, et al "Long-term effectiveness of human papillomavirus vaccination: Implications for future reduction in cancer" Ann Intern Med 2022; DOI:10.7326/M22-1309.