Clinical and economic burden of HPV-related cancers in the US veteran population

Abstract Background Human papillomavirus (HPV) is one of the most common sexually transmitted infection in the United States and can lead to cervical, vulvovaginal, anal, penile, and oropharyngeal cancers. Compared with the general population, US military members are at a higher risk of HPV-related conditions, yet vaccination rates are relatively low in this population. As many service members may not be diagnosed with HPV-related cancers until after they leave active service, the objective of this study was to determine the incidence, prevalence, and economic burden of HPV-related cancers among US veterans. Methods The study used the 2014–2018 Veterans Health Administration (VHA) database to identify newly diagnosed adult patients (cases) with HPV-related cancers, including cervical, vulvovaginal, anal, penile, and oropharyngeal cancers. Cases were matched by age, race, and sex to patients without HPV related cancer (controls). Outcome measures included annual incidence, prevalence, health care resource utilization (HCRU), and costs. These outcomes were calculated from the index date (first cancer diagnosis) through the earliest of 24 months, death, or end of study period. Adjusted results were examined using generalized linear models. Results The annual prevalence and incidence rates of HPV-related cancers ranged from 43 (anal) to 790 (oropharyngeal) cases per million (CPM), and four (anal) to 131 (cervical) CPM, respectively. Compared with controls, cases had significantly higher annual HCRU. Mean numbers of annual inpatient hospitalizations were several times higher compared to controls (cervical: 6.7-times (×); vulvovaginal: 2.7×; penile: 6.6×; oropharyngeal: 10.2×; and anal: 14.9×; all p < 0.01). Similarly, cases had significantly higher all-cause healthcare costs vs. matched controls across all cancer types: cervical ($24,252 vs. $10,402), vulvovaginal ($34,801 vs. $10,913), penile ($42,772 vs. $9,139), oropharyngeal ($82,763 vs. $10,017), and anal ($98,146 vs. $8,339); (all p < 0.01). Conclusions HPV-related cancers may cause significant clinical and economic burden within the VHA system. Given the consequences of HPV-related cancers among veterans who did not have access to the vaccine, HPV vaccination of active military and eligible veterans should be considered a healthcare priority.

[1]  C. Helfrich,et al.  Factors Associated With Low-Value Cancer Screenings in the Veterans Health Administration , 2021, JAMA network open.

[2]  A. Borkowski,et al.  Cervical Cancer Screening in South Florida Veteran Population, 2014 to 2020: Cytology and High-Risk Human Papillomavirus Correlation and Epidemiology , 2021, Cureus.

[3]  D. Kapp,et al.  HPV associated cancers in the United States over the last 15 years: Has screening or vaccination made any difference? , 2021 .

[4]  I. Spicknall,et al.  Sexually Transmitted Infections Among US Women and Men: Prevalence and Incidence Estimates, 2018. , 2021, Sexually transmitted diseases.

[5]  M. Saraiya,et al.  Assessing Impact of HPV Vaccination on Cervical Cancer Incidence among Women Aged 15–29 Years in the United States, 1999–2017: An Ecologic Study , 2020, Cancer Epidemiology, Biomarkers & Prevention.

[6]  A. Jacobson,et al.  Socioeconomic and Racial Disparities and Survival of Human Papillomavirus–Associated Oropharyngeal Squamous Cell Carcinoma , 2020, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[7]  Agust Ingi Agustsson,et al.  Final analysis of a 14-year long-term follow-up study of the effectiveness and immunogenicity of the quadrivalent human papillomavirus vaccine in women from four nordic countries , 2020, EClinicalMedicine.

[8]  S. J. Henley,et al.  Human Papillomavirus–Attributable Cancers — United States, 2012–2016 , 2019, MMWR. Morbidity and mortality weekly report.

[9]  D. Ekwueme,et al.  Updated medical care cost estimates for HPV-associated cancers: implications for cost-effectiveness analyses of HPV vaccination in the United States , 2019, Human vaccines & immunotherapeutics.

[10]  Jiaxin Wu,et al.  Tobacco and oral squamous cell carcinoma: A review of carcinogenic pathways , 2019, Tobacco induced diseases.

[11]  W. Chan,et al.  Mean treatment cost of incident cases of penile cancer for privately insured patients in the United States. , 2019, Urologic oncology.

[12]  C. Tarney,et al.  Human Papillomavirus Vaccination Rates of Military and Civilian Male Respondents to the Behavioral Risk Factors Surveillance System Between 2013 and 2015. , 2019, Military medicine.

[13]  Sritha Rajupet,et al.  Using Veterans Affairs Medical Center (VAMC) data to identify missed opportunities for HPV vaccination , 2019, Human vaccines & immunotherapeutics.

[14]  D. Lairson,et al.  Health Care Costs of Anal Cancer in a Commercially Insured Population in the United States , 2018, Journal of managed care & specialty pharmacy.

[15]  FDA approves expanded use of Gardasil 9 to include individuals 27 through 45 years old , 2018, Case Medical Research.

[16]  S. Taubman,et al.  Human papillomavirus vaccine initiation, coverage, and completion rates among U.S. active component service members, 2007-2017. , 2018, MSMR.

[17]  S. J. Henley,et al.  Trends in Human Papillomavirus–Associated Cancers — United States, 1999–2015 , 2018, MMWR. Morbidity and mortality weekly report.

[18]  D. Au,et al.  Accessing Care Through the Veterans Choice Program: The Veteran Experience , 2018, Journal of General Internal Medicine.

[19]  J. Buechel Vaccination for Human Papillomavirus: Immunization practices in the U.S. military , 2018, Clinical journal of oncology nursing.

[20]  L. Alemany,et al.  Human papillomavirus-related oropharyngeal cancer , 2017, Annals of oncology : official journal of the European Society for Medical Oncology.

[21]  W. Chan,et al.  Medical Care Cost of Oropharyngeal Cancer among Texas Patients , 2017, Cancer Epidemiology, Biomarkers & Prevention.

[22]  C. von Buchwald,et al.  Quality of life in survivors of oropharyngeal cancer: A systematic review and meta-analysis of 1366 patients. , 2017, European journal of cancer.

[23]  K. Bilimoria,et al.  Initial Public Reporting of Quality at Veterans Affairs vs Non–Veterans Affairs Hospitals , 2017, JAMA internal medicine.

[24]  W. Chan,et al.  Mean direct medical care costs associated with cervical cancer for commercially insured patients in Texas. , 2017, Gynecologic oncology.

[25]  S. J. Henley,et al.  Human Papillomavirus-Associated Cancers - United States, 2008-2012. , 2016, MMWR. Morbidity and mortality weekly report.

[26]  W. Ahrens,et al.  Combined effects of smoking and HPV16 in oropharyngeal cancer. , 2016, International journal of epidemiology.

[27]  S. Shay,et al.  Characteristics of Human Papillomavirus-Associated Head and Neck Cancers in a Veteran Population. , 2015, JAMA otolaryngology-- head & neck surgery.

[28]  Maeve P. Carey,et al.  Veterans Access, Choice, and Accountability Act of 2014 (H.R. 3230; P.L. 113-146) , 2015 .

[29]  M. Remacle,et al.  Recurrent respiratory papillomatosis by HPV: review of the literature and update on the use of cidofovir , 2014, Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale.

[30]  B. Agan,et al.  Human papillomavirus seroprevalence among men entering military service and seroincidence after ten years of service. , 2013, MSMR.

[31]  G. Rees,et al.  Quality of life valuations of HPV-associated cancer health states by the general population , 2012, Sexually Transmitted Infections.

[32]  D. Lowy,et al.  Estimates of the annual direct medical costs of the prevention and treatment of disease associated with human papillomavirus in the United States. , 2012, Vaccine.

[33]  E. Yano,et al.  Access to Care for Women Veterans: Delayed Healthcare and Unmet Need , 2011, Journal of general internal medicine.

[34]  David W. Brown Smoking Prevalence among US Veterans , 2010, Journal of general internal medicine.

[35]  K. Nichol,et al.  Health‐Related Quality of Life, Functional Impairment, and Healthcare Utilization by Veterans: Veterans' Quality of Life Study , 2005, Journal of the American Geriatrics Society.

[36]  W. Chan,et al.  Mean medical costs associated with vaginal and vulvar cancers for commercially insured patients in the United States and Texas. , 2018, Gynecologic oncology.

[37]  F. Alawi,et al.  Human Papillomavirus and Oropharyngeal Cancer. , 2018, Dental clinics of North America.

[38]  Jan Horsky,et al.  Accuracy and Completeness of Clinical Coding Using ICD-10 for Ambulatory Visits , 2017, AMIA.

[39]  Carrie M. Farmer,et al.  Comparing VA and Non-VA Quality of Care: A Systematic Review , 2016, Journal of General Internal Medicine.

[40]  M. Laufer,et al.  Human Papillomavirus (HPV), HPV-Related Disease, and the HPV Vaccine. , 2008, Reviews in obstetrics & gynecology.

[41]  W H Foege,et al.  Centers for Disease Control , 1981, Journal of public health policy.