LAUSR

Infection with human papillomavirus (HPV) is associated with 6 cancer types: cervical squamous cell carcinoma and adenocarcinoma, as well as oropharyngeal, anal, vulvar, vaginal, and penile squamous cell carcinoma. Although rates of cervical cancer decreased after the adoption of population-level screening programs, a recent study found a 2.36% annual increase in all HPV-related cancer types between 2001 and 2017 in the United States, with an incidence of HPV-associated cancer of 13.68 cases per 100000 among women and 11 cases per 100000 among men (1). For cervical cancer, we have effective screening programs and treatments of cervical precancer, but significant disparities in access and outcomes persist (2). Oropharyngeal cancer has outpaced cervical cancer to become the most common HPV-associated cancer over the past few decades. However, for oropharyngeal cancer and other HPV-associated cancer types, there is either no detectable precancerous stage or no widely available screening program. Primary prevention of HPV infection through vaccination is the best strategy to prevent most HPV-associated cancer cases. In their article, Rosenblum and colleagues (3) report a study that describes cross-sectional HPV prevalence through 2018 among a national sample of sexually experienced individuals and found a 90% reduction in cervical, vaccine-type HPV infections among vaccinated females. They also noted a 74% reduction in such infections in unvaccinated females, indicating herd immunity. These data are consistent with other sources, which also suggest substantial reductions in vaccine-type HPV infections and precancer among vaccinated populations (4). Recent data also indicate near elimination of cervical cancer diagnosed before age 30 years among women who received on-time vaccination (5). One recent study with an 11-year follow-up of individuals enrolled in HPV vaccination trials compared with the general population found 17 cases of HPV-related cancer in unvaccinated individuals and 0 in vaccinated individuals, an estimated 100% vaccine effectiveness against all HPV-related cancer (6). In addition, HPV infections are associated with pregnancy complications, and recent data indicate reductions in preterm births and small-for-gestational-age infants in populations with high HPV vaccination rates (7). In contrast to sharp decreases in vaccine-type HPV infections, Rosenblum and colleagues (3) found no significant change in the prevalence of non–vaccine-type HPV infections. This finding has 2 important implications. First, this indicates that vaccine-type HPV infections are not being replaced with other oncogenic HPV infections. Early in the vaccine era, concerns were raised that HPV vaccine effectiveness could be compromised by increases in infections with other oncogenic subtypes; this study provides evidence that this is not the case. Second, these data indicate that the decreases seen in vaccine-type infections are related to vaccination, not other factors. The authors noted similar numbers of sexual partners and similar prevalence of non–vaccine-type HPV infection in the preand postvaccine eras. Thus, the behavior-associated risk for acquiring vaccine-type HPV infections likely remained stable over time, providing further evidence that decreases in vaccine-type HPV infections appear to be a direct result of vaccination. Of note, the authors attribute the increases in vaccine effectiveness from the 2007-to-2010 to the 2011-to-2014 era to higher rates of vaccination earlier in adolescence. This provides yet more evidence for the long-term effectiveness of HPV vaccination when given on time, ideally before the 13th birthday. As Rosenblum and colleagues also noted (3), the COVID-19 pandemic has led to decreased rates of HPV vaccination and reversed much of the progress made in recent years. Rates of HPV vaccination have lagged behind those of the tetanus–diphtheria–pertussis booster and the meningococcal vaccine since HPV vaccination was introduced in 2007 (8). 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 (9, 10). Even as adolescents return for well visits and routine vaccinations, 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, with a shortfall from which it may take a decade to recover (9). As we aim to rebuild health care services in the postpandemic era, we have over a decade of research on how to effectively provide HPV vaccinations to children and adolescents in the United States. Several practices are consistently associated with improvement in HPV vaccination rates (10). The first of these, a strong provider recommendation, is defined as unambiguously stating that a child is due for vaccination at the current visit (for example, “Your child is due for an HPV vaccine today”). The second, standing orders, allows nurses and licensed medical assistants to give vaccinations that are due without requiring interaction with a physician. The third, reminder and recall programs, uses population management systems to remind patients when vaccines are due and recall them for appointments. Finally, multilevel interventions combine improvements at the patient, clinician, and health care system levels and can lead to sustained improvements. 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.