HPV Strains Covered by the Vaccine Have Declined Greatly in the US

Pam Harrison

May 16, 2022

Twelve years after the human papillomavirus (HPV) vaccination program was introduced in the United States, the overall prevalence of cancer-causing HPV strains covered by the vaccine dropped by 85% among females — 90% among vaccinated females and 74% among unvaccinated females — a strong sign of herd immunity, a new analysis of a nationally representative database is showing.

"HPV vaccination is working well," Hannah Rosenblum, MD, Centers for Disease Control and Prevention, Atlanta, Georgia, told Medscape Medical News in an email.

Dr Hannah Rosenblum

"Twelve years after introduction of HPV vaccination in the US, national data demonstrate increasing impact among females, and strong herd effects among unvaccinated females," she added. "[Although] vaccination coverage and completion of the recommended dose in the US is lower than coverage with other adolescent vaccinations, HPV vaccination is the best way to prevent HPV infections that can lead to several cancers in both females and male."

The study was published online today in Annals of Internal Medicine.


The authors used data from the National Health and Nutrition Examination Survey (NHANES) to examine the four HPV types in the quadrivalent vaccine before 2003 and 2006 (the pre-vaccine era) and then again between 2007-2010, 2011-2014, and 2015-2018 (the vaccine era). For females, they analyzed demographic and HPV prevalence data across each 4-year era.

"Analyses were limited to sexually experienced participants to ensure that all those included had an opportunity for HPV exposure and to participants aged 14 to 24 years with adequate self-collected cervicovaginal specimens," the authors explain.

This resulted in a sample size of 3197 females. Demographic and HPV prevalence data were also collected from males but only during the 2013-2016 era, because those are the only years for which male HPV typing data are available in NHANES.  Again, analyses were limited to sexually experienced males aged 14-24 years with adequate self-collected penile specimens, which resulted in a sample size of 661 males.

Over the 12 years of follow-up for females, there was a steady increase in females reporting having received at least one dose of the HPV vaccine —from slightly over 25% during 2007-12 to 59% during 2015-2018. The percentage of males who reported having at least one HPV dose also increased, from 29.5% in 2016 to 34.5% in 2018.

During the earliest vaccine era (2007-2010), the prevalence of the four HPV strains covered by the vaccine was 7.3% among vaccinated females compared with 20.4% among unvaccinated females. "By 2015 to 2018, the prevalence was 2.8% (prevalence ratio [PR] 0.16; 95% CI, 0.07 - 0.39). The prevalence of the four vaccine-covered types was only 1.9% in vaccinated females compared with 4.8% in unvaccinated females (PR, 0.40; 95% CI, 0.11 - 1.41).

In contrast, the prevalence of HPV types that were not covered by the vaccine showed little change — from 51.1% in the pre-vaccine era to 47.6% during 2015-2018 (PR, 0.93; 95% CI, 0.80 - 1.08). The authors considered this a good sign because it indicates that vaccine-type HPV infections are not being replaced with other oncogenic HPV infections. Between 2013 and 2016, the difference in the prevalence of the four HPV vaccine types was smaller at 1.8% among vaccinated males and 3.5% among unvaccinated males (PR, 0.49; 95% CI, 0.11 - 2.20).

Again, the prevalence of non-HPV vaccine types was not significantly different between vaccinated and unvaccinated males: 30.7% vs 34.3%.

During the vaccine era, effectiveness for females ranged from 60% to 84%. For males, vaccine effectiveness could only be evaluated for the single 4-year period from 2013 to 2016, and it was estimated at 51%. Rosenblum noted that vaccine efficacy estimates were lower on this national survey than the almost 100% efficacy rates observed in clinical trials in both males and females.

"This might be due in part to many participants receiving the vaccine at an older age than is recommended when they could have been infected [with HPV] at the time of vaccination," Rosenblum said. She also noted that because males were incorporated into the HPV vaccination program years after females, they likely also experienced strong herd effects from the vaccine, making it challenging to estimate vaccine effectiveness.

Rosenblum also noted that there have already been documented declines in cervical precancers and high-grade vulvar and vaginal precancers, as well as genital warts and juvenile-onset recurrent respiratory papillomatosis. At the same time, the incidence of cervical precancers has recently declined among US females in their late teens and early 20s — "likely reflecting the impact of vaccination," she said.

"This study is good news for the US HPV vaccination program, and all efforts are needed to ensure that children and adolescents receive routinely recommended vaccinations [including vaccination against HPV]," Rosenblum added.

Editorial Comment

Commenting on the findings, Rebecca Perkins, MD, Boston University School of Medicine, Boston, Massachusetts, and colleagues point out that the COVID-19 pandemic has led to disruptions in HPV vaccination programs and has reversed 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," Perkins and colleagues write in an accompanying editorial.

Thus, the need to compensate for the cumulative deficit of missed vaccinations over the past 2 years has created a "serious and urgent threat" to cancer prevention efforts — "a shortfall from which it may take a decade to recover," the editorialists predict. To try and reverse this trend, several practices have been shown to improve HPV vaccination rates.

The first is a strong provider recommendation such as, "Your child is due for an HPV vaccine today." The second is to give standing orders to allow nurses and medical assistants to administer vaccinations without requiring intervention by a physician. Lastly, programs to remind patients when vaccines are due and to recall them for appointments also work well.

"Using evidence-based methods and redoubling our efforts to prioritize HPV vaccination will be crucial to ensuring that we do not lose a generation to preventable HPV-associated cancer," write Perkins and colleagues.

The study authors and editorialists have disclosed no relevant financial relationships.

Ann Intern Med. Published online May 16, 2022. Abstract

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