By Alexandra Morell, MD
Synopsis: A longitudinal, cross-sectional cohort study of 113,344 participants demonstrated that lack of health insurance, lack of stable employment, and lower income were significantly associated with decreased human papillomavirus vaccination uptake in women aged 18-47 years residing in the United States.
Source: Wong TY, Adzibolosu NK, Mattei LH, et al. Disparities in contemporary human papilloma virus vaccination uptake among adult women living in the United States: An All of Us Research Program study. Gynecol Oncol. 2024;191:100-105.
Cervical cancer is the most common human papillomavirus (HPV)-associated cancer in the United States.1 More than 13,000 women are diagnosed with cervical cancer each year.2 In addition, 91% of cervical cancers are attributed to HPV infection.
The U.S. Food and Drug Administration (FDA) currently has approved three HPV vaccines, each of which covers a different number of HPV serotypes. The HPV vaccine is highly effective in the prevention of cervical cancer. However, despite the vaccine’s widespread availability in the United States since 2006, and cervical cancer screening, the age-adjusted rate of new cervical cancer diagnoses has remained relatively stable since 2010.3
HPV vaccination rates have been lower than anticipated, with approximately 54% of women and 49% of men receiving all recommended doses compared with the Centers for Disease Control and Prevention’s goal of 80%.2,4 In addition, it is well known that there are disparities in cervical cancer rates and cervical cancer-associated mortality affecting racial and ethnic minority populations, rural populations, and socioeconomically disadvantaged populations.5,6 The primary objective of this study was to assess the effect of sociodemographic factors on HPV vaccination uptake in U.S. adult women.
This was an Institutional Review Board (IRB)-approved cross-sectional cohort study using data from the National Institutes of Health (NIH) All of Us (AoU) Program. This program started enrollment in May 2018 and recruits adult participants from historically underrepresented groups in medical research from more than 300 sites in the United States.
This study included participants aged 18 to 47 years, assigned female at birth, enrolled in the AoU program over a five-year period (May 2018 to April 2023). AoU data extracted from electronic medical records include physical measurements (weight, height), biospecimens, biometric recordings, and survey data. For statistical analyses, bivariable and multivariable analyses were performed.
During the study period, 113,344 participants met criteria for inclusion, with 3,575 (3.2%) receiving at least one HPV vaccination. A total of 60,594 (53.5%) participants self-identified as a racial or ethnic minority, compared with 52,750 (46.5%) participants self-identifying as non-Hispanic white (NHW). Of the patients self-identifying as a racial or ethnic minority, 26% identified as Hispanic, 17% identified as non-Hispanic Black (NHB), 5.7% identified as other, and 4.8% identified as Asian. The median age of vaccinated patients was 26 years. Approximately two-thirds of participants reported stable full- or part-time employment and more than 90% of participants were insured.
Regarding sociodemographic factors associated with HPV vaccination, participants who self-identified as Hispanic were significantly more likely to be vaccinated than NHW participants (odds ratio [OR], 2.19; 95% confidence interval [CI], 2.02-2.36). In addition, participants born outside the United States were more likely to be vaccinated compared with participants born in the United States (OR, 1.52; 95% CI, 1.40-1.64).
Participants lacking stable employment (OR, 0.85; 95% CI, 0.79-0.91), without health insurance (OR, 0.32; 95% CI, 0.26-0.40), and with lower household income (OR, 0.87; 95% CI, 0.79-0.97) were less likely to receive the HPV vaccination after adjusting for age. Education beyond a high school degree was associated with lower HPV vaccination uptake (OR, 0.93; 95% CI, 0.77-0.89). In addition, obesity and morbid obesity were associated with decreased odds of HPV vaccination (OR, 0.75; 95% CI, 0.69-82 and OR, 0.55; 95% CI, 0.49-63, respectively).
Regarding additional economic factors associated with HPV vaccination, those reporting concern about housing insecurity within the last six months were less likely to receive the HPV vaccination (OR, 0.67; 95% CI, 0.61-0.74). HPV vaccination uptake did not differ between those who expressed concern regarding food insecurity (OR, 0.83; 95% CI, 0.68-1.00), childcare (OR, 0.90; 95% CI, 0.74-1.08), or transportation (OR, 0.97; 95% CI, 0.82-1.14), or reported further distance from healthcare services (OR, 0.86; 95% CI, 0.66-1.10). Lastly, participants who reported cost as a barrier to healthcare had a decreased odds of receiving HPV vaccination (OR, 0.82; 95% CI, 0.73-0.93).
Regarding behavioral health factors and HPV vaccination, uptake of vaccination was significantly lower in participants with a personal or family history of depression (OR, 0.81; 95% CI, 0.71-0.92). Participants with a personal or family history of alcohol use disorder (OR, 0.79; 95% CI, 0.66-0.93) or a personal or family history of illicit drug use (OR, 0.59; 95% CI, 0.43-0.77) also were significantly less likely to receive the HPV vaccination. Lastly, participants reporting use of greater than 100 cigarettes during their lifetime also were significantly less likely to have undergone HPV vaccination than nonsmokers (OR, 0.44; 95% CI, 0.40-0.49).
Commentary
The American College of Obstetricians and Gynecologists (ACOG) currently recommends HPV vaccination of girls and boys at ages 11-12 years (but can be given starting at 9 years) with the 9-valent vaccine.2 The 9-valent vaccine protects against HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58. In addition, ACOG recommends catch-up vaccination in adolescent girls and young women ages 13-26 years who were not vaccinated previously regardless of sexual activity, exposure to HPV, or sexual orientation. Two doses separated by six months are recommended if the first dose is given before age 15 years. After age 15 years, the vaccine is given in a three-dose series at 0, 2, and 6 months.
Prior to 2018, the vaccine was not recommended beyond age 26 years. However, starting in October 2018, the FDA approved the HPV vaccine through age 45 years. ACOG currently recommends a shared decision-making approach for adult women aged 27-45 years who have never received prior HPV vaccination about whether to receive the vaccine, considering individual risk for new HPV infection acquisition.2,7,8
In a randomized, double-blind, Phase III clinical trial of more than 14,000 participants aged 16-26 years comparing the 9-valent to the 4-valent HPV vaccine, the 9-valent vaccine was 96.3% effective at preventing greater than CIN2 (defined as cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, vaginal intraepithelial neoplasia grade 2 or 3, and vulvar intraepithelial neoplasia grade 2 or 3) related to HPV 31, 33, 45, 52, or 58 infection.9
In addition, the 9-valent vaccine was 96.0% effective in preventing six-month persistent HPV infection of those same serotypes. Both the 4-valent vaccine and the 9-valent vaccine were effective at preventing greater than CIN2 related to HPV 6, 11, 16, and 18, with only one case out of 5,823 participants receiving the 9-valent vaccine and one case out of 5,832 participants receiving the 4-valent vaccine.
Furthermore, a Phase III open-label clinical trial comparing the immunogenicity of HPV vaccination in women aged 16-26 years vs. 27-45 years found similar anti-HPV human genomic mean titers (an indication of seroconversion) between the two age groups, suggesting the HPV vaccination also should be highly effective in women older than 27 years of age who receive the vaccine.10 Given the effectiveness of the vaccine at preventing pre-invasive cervical disease and, therefore, cervical cancer, understanding factors associated with decreased rates of HPV vaccination is important.
In this study, with a cohort composed of both participants aged 18-26 years (in whom catch-up HPV vaccination is recommended by ACOG) and participants aged 27-45 years (where shared decision-making is recommended by ACOG), lack of stable employment, lack of insurance, and lower household income were associated with decreased uptake of HPV vaccination.
A previous cross-sectional study of 2,722 individuals aged 18-45 years similarly demonstrated that income level, employment, and insurance status were associated with HPV vaccination in this age demographic.11 In addition, a history of depression, anxiety, alcohol use disorder, substance use disorder, smoking, and obesity also were associated with decreased uptake of HPV vaccination.
Of note, the HPV vaccination rate in this study was very low at 3.2%. However, it is important to keep in mind that this study did not include patients younger than 18 years of age who are a target population for the initial HPV vaccination.
The authors also noted that it was unknown how many women received an HPV vaccination at the recommended timepoint. Despite this limitation, this study still highlights several factors associated with decreased HPV vaccination rates.
OB/GYNs are uniquely positioned to help counsel and educate patients about HPV vaccination as a method for reducing the risk of cervical cancer. Continuing to understand factors associated with HPV vaccination, both in the target population of patients aged 11-12 years and in the catch-up setting from ages 13-45 years, can help us identify gaps in vaccination and help with developing strategies to increase HPV vaccine uptake.
Alexandra Morell, MD, is Adjunct Instructor, Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY.
References
- Centers for Disease Control and Prevention. United States Cancer Statistics. Cancers associated with human papillomavirus. https://www.cdc.gov/united-states-cancer-statistics/publications/hpv-associated-cancers.html?CDC_AAref_Val=https://www.cdc.gov/cancer/uscs/about/data-briefs/no31-hpv-assoc-cancers-UnitedStates-2015-2019.htm
- American College of Obstetricians and Gynecologists’ Committee on Adolescent Health Care, American College of Obstetricians and Gynecologists’ Immunization, Infectious Disease, and Public Health Preparedness Expert Work Group. Human papillomavirus vaccination: ACOG Committee Opinion, Number 809. Obstet Gynecol. 2020;136(2):e15-e21.
- National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Cervical Cancer. https://seer.cancer.gov/statfacts/html/cervix.html
- Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices. Evidence to recommendations for HPV vaccination of adults, ages 27 through 45 years. Published Aug. 7, 2024. https://www.cdc.gov/acip/evidence-to-recommendations/HPV-adults-etr.html
- Buskwofie A, David-West G, Clare CA. A review of cervical cancer: Incidence and disparities. J Natl Med Assoc. 2020;112(2):229-232.
- Tjioe KC, Miranda-Galvis M, Johnson MS, et al. The interaction between social determinants of health and cervical cancer survival: A systematic review. Gynecol Oncol. 2024;181:141-154.
- Oshman LD, Davis AM. Human papillomavirus vaccination for adults: Updated recommendations of the Advisory Committee on Immunization Practices (ACIP). JAMA. 2020;323(5):468-469.
- Meites E, Szilagyi PG, Chesson HW, et al. Human papillomavirus vaccination for adults: Updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2019;68(32):698-702.
- Joura EA, Giuliano AR, Iversen OE, et al. A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med. 2015;372(8):711-723.
- Joura EA, Ulied A, Vandermeulen C, et al. Immunogenicity and safety of a nine-valent human papillomavirus vaccine in women 27-45 years of age compared to women 16-26 years of age: An open-label phase 3 study. Vaccine. 2021;39(20):2800-2809.
- Arevalo M, Brownstein NC, Whiting J, et al. Factors related to human papillomavirus vaccine uptake and intentions among adults aged 18-26 and 27-45 years in the United States: A cross-sectional study. Cancer 2023;129(8):1237-1252.
A longitudinal, cross-sectional cohort study of 113,344 participants demonstrated that lack of health insurance, lack of stable employment, and lower income were significantly associated with decreased human papillomavirus vaccination uptake in women aged 18-47 years residing in the United States.
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