By Dabie Isiofia ’28
Human Papillomavirus (HPV) remains the predominant sexually transmitted infection (STI) in the United States, with 13 million diagnoses in 2023 (Centers for Disease Control and Prevention [CDC], 2024a, p. 1). Despite the introduction of an HPV vaccine with a 90% effectiveness rate in 2006, HPV persists as the most common STI among both men and women (Centers for Disease Control and Prevention [CDC], 2024b; Curtis, 2022). The primary cause for the discrepancy between the vaccine’s effectiveness and the stagnant change in HPV cases lies in the diminished impact of HPV on immunocompetent individuals who possess the ability to produce a normal immune response. According to the National Institutes of Health, most HPV infections regress within 1-2 years due to cell-mediated immunity, leading to only a small proportion of infections becoming severe in the majority of individuals (Cho et al., 2015). Consequently, vaccine recommendations by healthcare providers were not heavily prioritized in the past, exacerbating the severity of HPV infections among those with immunocompromised conditions, who are at higher risk of developing severe infections.
Severe HPV cases can lead to anal cancer, cervical cancer, oropharyngeal cancer, penile cancer, vaginal cancer, and vulvar cancer (National Cancer Institute [NCI], 2023a, What is HPV (human papillomavirus)?). The Centers for Disease Control and Prevention reports 37,000 HPV-related cancer diagnoses annually, with HPV responsible for approximately 91% of all cervical cancer diagnoses and over 80% of all cancer diagnoses in affected areas (Centers for Disease Control and Prevention [CDC], 2024c, Number of HPV-attributable cancer cases per year). The neglect of prioritizing vaccine recommendations has compounded the repercussions of HPV infections on individuals highly susceptible to significant complications.
Common cellular progression of cervical cancer induced by HPV. Adapted from the NIH 5
Among individuals with immunocompromised conditions, child cancer survivors (CCS) face an increased risk of developing HPV-related cancers, given their higher susceptibility to relapse and malignancies (Dixon et al., 2018). Females within the CCS population are 40% more likely and males are 150% more likely to develop HPV-related malignancies compared to the general US population (Ojha et al., 2013, p. 1). Despite these increased risks, CCS are among the least vaccinated populations against HPV. A 2020 study from the National Cancer Institute and research by Melissa A. Kluczynski (Kluczynski et al., 2024), a clinical research associate at the Roswell Park Comprehensive Cancer Center, indicates that while 58% of the general population is HPV vaccinated, less than 25% of CCS have received an HPV vaccination.
The low domestic HPV vaccination rates are a byproduct of the multi-step immunization process and vaccine hesitancy. The HPV vaccine is administered in a multi-dose series. The CDC recommends a two-dose series for individuals aged 9-14 years (0, 6-12 months) and a three-dose series (0, 1-2, 6 months) for immunocompromised patients or those aged 15-45 (Centers for Disease Control and Prevention [CDC], 2024d, Patient counseling). The need for multiple doses, combined with the stigmatization surrounding HPV and limited HPV education, contributes to the overall low national vaccination rates in the United States. Vaccine hesitancy further exacerbates these low immunization rates.
In 2019, Emilie Karafillakis and colleagues from the Department of Epidemiology and Population Health at the London School of Hygiene & Tropical Medicine conducted a study examining public mistrust and vaccine hesitancy towards the HPV vaccine in Europe, a region known for significant vaccine hesitancy (Karafillakis et al., 2016). Vaccine hesitancy, defined by the World Health Organization (WHO) SAGE working group, “pertains to behavior influenced by issues of confidence, complacency, and convenience.” Karafillakis’s study identified the primary causes of hesitancy as “a lack of confidence in vaccine safety, perceptions that vaccines do not work, distrust of information, and perceived low risks of vaccine-preventable diseases.”(Karafillakis et al., 2016, Discussion) This study highlights the critical role of miscommunication in fueling vaccine hesitancy.
HPV vaccine uptake among male vs. female offspring between 9 and 11 years of age in Italy (n = 427). Adapted from the NIH.14
These findings are relevant to the U.S., where similar issues persist, though on a smaller scale. Additional challenges in the U.S., such as the inability to attend multiple appointments to complete the vaccine series and parental reluctance to discuss sexuality and STIs with their children, further hinder adolescent vaccination. While these challenges affect CCS, there are other specific factors that further reduce vaccination rates within this population.
The primary barriers impeding CCS vaccination rates are a lack of provider recommendation and a misunderstanding by providers of their responsibility to recommend vaccination. While 95% of general care physicians made HPV immunization recommendations to their patients aged 9-18 years, the rates of hematology/oncologists and nurse practitioners (HOCP) who make recommendations are vastly lower (Lake, 2022). In a study conducted by Meagan E. Miller, Division of Hematology/Oncology, Department of Pediatrics at Indiana Medical School (Miller, 2023, Abstract), found that when interviewing 20 HCOP, despite 90% of the sample expressing support for HPV vaccination for CCS, only 45% of them recorded giving recommendations to their patients. This disparity arises because HCOPs rely on general care physicians to provide HPV recommendations for the bulk of their patients. However, HOCPs have misunderstood their responsibility in making recommendations. Upon a cancer diagnosis, pediatric cancer patients often cease seeing their general care physician and solely receive treatment and checkups from HCOPs. However, as HOCPs operate with the mindset that HPV recommendations are the responsibility of general care physicians, pediatric cancer patients are often not given HPV vaccine recommendations and are thus less likely to begin their immunization series. The results of Miller’s study have pushed more hospitals and cancer centers to require their HCOPs to make HPV recommendations to their patients. However, as Miller’s study targeted identifying an issue and proposing a potential solution, the study did not look into the actual results of increasing these recommendations within cancer centers. While records from the past four years have shown an increase in HPV immunization rates among CCS proportionally to a rise in the amount of HOCPs providing recommendations, those rates became stagnant as of 2022, with still less than 25% of CCS being vaccinated (Kluczynski et al., 2024). This highlights that increasing the proportion of providers making recommendations is only a partial solution. To enhance long-term CCS immunization rates, this increase must be coupled with more effective recommendation strategies.
Model of clinician-level and system-level barriers to HPV counseling and provision. Adapted from the NIH.15
The disproportionately low immunization rates among childhood cancer survivors remain a critical issue in the effort to achieve national HPV immunity. The challenges faced by the CCS population are not due to difficulties in vaccine development, but ineffective vaccine distribution methods for this group. As awareness of these disparities grow, it is crucial for research to focus on identifying new strategies to address and reform these issues. While past studies have introduced reforms that increased CCS immunization rates, progress has recently stagnated, with rates still less than half those of the general population. Future research must continue exploring alternative approaches to reduce this disparity.
Dabie Isiofia ’28 is a staff writer at The Princeton Medical Review. He can be reached at di1200@princeton.edu
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