Updated medical care cost estimates for HPV-associated cancers: implications for cost-effectiveness analyses of HPV vaccination in the United States

Figures & data

Figure 1. Flow diagram illustrating the identification of studies providing updated medical care cost estimates for HPV-associated cancers in the United States.

Table 1. Medical care costs for HPV-associated cancers in the United States: Estimates from recent studies (2012 to 2018), compared to previous studies (before 2012) commonly cited in cost-effectiveness analyses of HPV vaccination.

	Recent cost studies (2012 to 2018)			Previous cost studies (before 2012)
Type of HPV-associated cancer	Study author (year of publication)	Data source*	Medical care cost estimate	Study author (year of publication)	Data source**	Medical care cost estimate (range)
Anal	Deshmukh (2018)^Citation12	SEER-Medicare data	$52,700	Hu and Goldie (2008)^Citation34	Ontario (Canada) health insurance data; colorectal cancer costs	$38,200 ($18,500 to $74,200)
Anal	Wu (2018)^Citation18	U.S. national health care claims	$133,300
Cervical	Lairson (2017)^Citation14	Texas health care claims	$82,100	Kim and Goldie (2008);^Citation1 Insinga (2008)^Citation35	National health care claims; Large U.S. health plan	$43,400 ($34,300 to $58,800)
Oropharyngeal	Lairson (2017)^Citation13	Texas health care claims	$146,100	Hu and Goldie (2008)^Citation34	SEER-Medicare data	$45,600 ($21,200 to $64,700)
Oropharyngeal	Sher (2016)^Citation19	Medicare payment schedules	$65,000***
Vaginal	Fu (2018)^Citation15	U.S. national health care claims	$144,400	Hu and Goldie (2008)^Citation34	Michigan private payer reimbursement rates	$28,600 ($21,500 to $36,100)
Vulvar	Fu (2018)^Citation15	U.S. national health care claims	$59,400	Hu and Goldie (2008)^Citation34	Medicare fee schedule, HCUP	$24,900 ($16,400 to $33,500)

Cost estimates have been updated to 2018 U.S. dollars using the health care component of the price index for personal consumption expenditures.

SEER: Surveillance, Epidemiology, and End Results. HCUP: Healthcare Cost and Utilization Project

*Data sources, recent cost studies:

Deshmukh (2018) used the SEER program cancer registries, covering about 28% of the US population. About 93% of persons aged 65 years and older in the SEER files are matched to Medicare files. Only fee-for-services care claims are included in the SEER-Medicare data (e.g., claims from health maintenance enrollees are not included). Wu (2018) used a large commercial claims database (MarketScan). Both Lairson studies (cervical cancer, oropharyngeal cancer) used MarketScan data (92% of patients were commercially insured, 8% were in Medicare Supplement plans), and focused on patients living in Texas diagnosed with cancer. Sher (2016) used 2015 Chicago-area Medicare payment schedules. Fu (2018) used MarketScan claims data on privately insured Americans, and the database included over 90 million insured over the 2011–2014 study period. The literature search yielded no studies of the medical care cost per case for penile cancer.

**Data sources, previous cost studies:

The Hu and Goldie (2008) cost estimates were calculated as follows: the anal cancer cost estimate was based on a cost study of rectal cancer in Canada⁴¹ and was consistent with a previous study⁴² that approximated anal cancer costs using colon cancer cost estimates⁴³ derived from data from a health maintenance organization in Washington State. The oropharyngeal cancer cost estimate was obtained from a previous study⁴⁴ that used SEER-Medicare data. The vaginal cancer cost estimate was calculated using data from a cost-effectiveness analysis of a vaginal cancer screening,⁴⁵ which provided cost estimates for therapeutic procedures for vaginal cancer based on third party private payer reimbursement rates in Michigan. The vulvar cancer cost estimate was calculated based on the medical procedures required for treatment of vulvar cancer, and costs for these procedures were based on the 2004 Medicare Fee Schedule for physician fees and Healthcare Cost and Utilization (HCUP) data for hospitalization-related costs. The cervical cancer cost estimate was obtained from Chesson (2012),³³ which combined two estimates from two previous studies: Insinga (2008), which used data from a large U.S. health plan and Kim and Goldie (2008), which used cervical cancer cost estimates from a previous study⁴⁶ based in part on MarketScan data.

***The Sher (2016) estimate for oropharyngeal cancer of $65,000 is for treatment with transoral robotic surgery; a cost of $52,400 was reported for treatment with primary chemoradiation therapy.

The recently published (2012 to 2018) cost studies reflect 2-year medical care costs per case, except the Deshmukh (2018) anal cancer cost estimate which reflects a lifetime cost per case estimate and the Sher (2016) cost estimate which reflects a 10-year time horizon. The estimates from the pre-2012 cost studies all reflect lifetime cost per case estimates.

The Hu and Goldie (2008) oropharyngeal cost estimate reflects costs for mouth and oropharyngeal cancers.

See manuscript text for selected examples of published cost-effectiveness studies that cite the pre-2012 cost estimates.

Table 2. Estimated vaccination costs, number of quality-adjusted life years (QALYs) gained, medical costs averted, and cost-effectiveness estimates for two HPV vaccination strategies in the United States, over a 100-year time horizon.

Item estimated	Routine vaccination of 12-year-olds		Routine vaccination of 12-year-olds plus catch-up through age 26 years
	Using previous (before 2012) cancer cost estimates	Using more recent (2012 to 2018) cancer cost estimates	Using previous (before 2012) cancer cost estimates	Using more recent (2012 to 2018) cancer cost estimates
Vaccination costs ($ billions)	14.6	14.6	48.6	48.6
Number of QALYs gained (thousands)	674	674	1,160	1,160
Non-cancer costs averted ($ billions)	6.5	6.5	10.7	10.7
Cancer costs averted ($ billions)	5.1	13.1	8.9	22.9
Net cost ($ billions)	3.0	−5.0	29.0	15.0
Incremental number of QALYs gained (thousands)*	674	674	486	486
Incremental cost ($ billions)*	3.0	−5.0	26.0	20.0
Incremental cost per QALY gained ($)*	4,500	< 0 (cost-saving)	53,500	41,100

*Incremental results for vaccination of 12-year-olds were calculated compared to no vaccination. Incremental results for vaccination of 12-year-olds plus catch-up through age 26 years were calculated as compared to vaccination of 12-year-olds.

Costs are in 2018 U.S. dollars. Vaccination strategies include all genders (including males and females). Non-cancer costs averted reflect averted costs for genital warts, cervical intraepithelial neoplasia, and recurrent respiratory papillomatosis. Net cost reflects vaccination costs minus averted cancer costs and averted non-cancer costs. The previous (lower) cancer cost estimates and the more recent (higher) cancer cost estimates are shown in Table 1. In order to illustrate the greatest potential impact of the more recent cancer cost estimates on the estimated cost-effectiveness of HPV vaccination, for anal cancer in the more recent (higher) cost scenario, we applied the $133,300 cost estimate by Wu (2018)¹⁸ rather than the $52,700 estimate by Deshmukh (2018).¹² Similarly, for oropharyngeal cancer, we applied the $146,100 cost estimate by Lairson (2017)¹³ rather than the $65,000 estimate by Sher (2016).¹⁹

Table 3. Sensitivity analysis: Estimated cost per quality-adjusted life year ($ per QALY) gained when applying cancer cost estimates from recent studies (2012 to 2018) and from older studies (before 2012), when other model parameters are varied.

	Routine vaccination of 12-year-olds		Routine vaccination of 12-year-olds plus catch-up through age 26 years
Parameter(s) varied in sensitivity analysis, in addition to varying cancer medical care cost assumptions	Using previous (lower) cancer cost estimates	Using more recent (higher) cancer cost estimates	Using previous (lower) cancer cost estimates	Using more recent (higher) cancer cost estimates
Base case (no parameters varied other than cancer costs)	4,500	< 0 (cost-saving)	53,500	41,100
Lower vaccination cost per series	900	< 0 (cost-saving)	41,800	29,400
Higher vaccination cost per series	8,100	< 0 (cost-saving)	65,000	52,600
Lower number of QALYs lost per health outcome	5,700	< 0 (cost-saving)	68,000	52,200
Higher number of QALYs lost per health outcome	2,400	< 0 (cost-saving)	29,100	22,300
Lower incidence of HPV-associated health outcomes	9,500	< 0 (cost-saving)	62,000	49,200
Higher incidence of HPV-associated health outcomes	< 0 (cost-saving)	< 0 (cost-saving)	43,200	31,400
Lower percentage of health outcomes attributable to HPV	10,400	< 0 (cost-saving)	68,800	56,200
Higher percentage of health outcomes attributable to HPV	< 0 (cost-saving)	< 0 (cost-saving)	40,900	28,500

Costs are in 2018 U.S. dollars. The estimated cost per QALY for vaccination of 12-year-olds was calculated compared to no vaccination. The estimated cost per QALY for vaccination of 12-year-olds plus catch-up through age 26 years was calculated compared to vaccination of 12-year-olds. See Tables 1 and 2 for additional information regarding the cancer costs applied in these analyses.

Deshmukh AA, Zhao H, Franzini L, Lairson DR, Chiao EY, Das P, Swartz MD, Giordano SH, Cantor SB. Total lifetime and cancer-related costs for elderly patients diagnosed with anal cancer in the United States. Am J Clin Oncol. 2018;41(2):121–27. doi:10.1097/COC.0000000000000238.

 PubMed Web of Science ®Google Scholar

Hu D, Goldie S. The economic burden of noncervical human papillomavirus disease in the United States. Am J Obstet Gynecol. 2008;198(5):500.e1–500.e7. doi:10.1016/j.ajog.2008.03.064.

 Web of Science ®Google Scholar

Wu CF, Xu L, Fu S, Peng HL, Messick CA, Lairson DR. Health care costs of anal cancer in a commercially insured population in the United States. J Manag Care Spec Pharm. 2018;24(11):1156–64. doi:10.18553/jmcp.2018.24.11.1156.

 PubMed Web of Science ®Google Scholar

Lairson DR, Fu S, Chan W, Xu L, Shelal Z, Ramondetta L. Mean direct medical care costs associated with cervical cancer for commercially insured patients in Texas. Gynecol Oncol. 2017;145(1):108–13. doi:10.1016/j.ygyno.2017.02.011.

 PubMed Web of Science ®Google Scholar

Kim JJ, Goldie SJ. Health and economic implications of HPV vaccination in the United States. N Engl J Med. 2008;359(8):821–32. doi:10.1056/NEJMsa0707052.

 PubMed Web of Science ®Google Scholar

Insinga RP, Ye X, Singhal PK, Carides GW. Healthcare resource use and costs associated with cervical, vaginal and vulvar cancers in a large U.S. health plan. Gynecol Oncol. 2008;111(2):188–96. doi:10.1016/j.ygyno.2008.07.032.

 PubMed Web of Science ®Google Scholar

Lairson DR, Wu CF, Chan W, Dahlstrom KR, Tam S, Sturgis EM. Medical care cost of oropharyngeal cancer among Texas patients. Cancer Epidemiol Biomarkers Prev. 2017;26(9):1443–49. doi:10.1158/1055-9965.EPI-17-0220.

 PubMed Web of Science ®Google Scholar

Sher DJ, Fidler MJ, Tishler RB, Stenson K, al-Khudari S. Cost-effectiveness analysis of chemoradiation therapy versus transoral robotic surgery for human papillomavirus-associated, clinical N2 oropharyngeal cancer. Int J Radiat Oncol Biol Phy. 2016;94(3):512–22. doi:10.1016/j.ijrobp.2015.11.006.

 PubMed Web of Science ®Google Scholar

Fu S, Lairson DR, Chan W, Wu CF, Ramondetta L. Mean medical costs associated with vaginal and vulvar cancers for commercially insured patients in the United States and Texas. Gynecol Oncol. 2018;148(2):342–48. doi:10.1016/j.ygyno.2017.12.019.

 PubMed Web of Science ®Google Scholar

Maroun J, Ng E, Berthelot JM, Le Petit C, Dahrouge S, Flanagan WM, Walker H, Evans WK. Lifetime costs of colon and rectal cancer management in Canada. Chronic Dis Can. 2003;24:91–101.

 PubMedGoogle Scholar

Goldie SJ, Kuntz KM, Weinstein MC, Freedberg KA, Palefsky JM. Cost-effectiveness of screening for anal squamous intraepithelial lesions and anal cancer in human immunodeficiency virus-negative homosexual and bisexual men. Am J Med. 2000;108:634–41.

 PubMed Web of Science ®Google Scholar

Taplin SH, Barlow W, Urban N, Mandelson MT, Timlin DJ, Ichikawa L, Nefcy P. Stage, age, comorbidity, and direct costs of colon, prostate, and breast cancer care. J Natl Cancer Inst. 1995;87:417–26.

 PubMed Web of Science ®Google Scholar

Lang K, Menzin J, Earle CC, Jacobson J, Hsu MA. The economic cost of squamous cell cancer of the head and neck: findings from linked SEER-Medicare data. Arch Otolaryngol Head Neck Surg. 2004;130(11):1269–75. doi:10.1001/archotol.130.11.1269.

 PubMed Web of Science ®Google Scholar

Fetters MD, Lieberman RW, Abrahamse PH, Sanghvi RV, Sonnad SS. Cost-effectiveness of pap smear screening for vaginal cancer after total hysterectomy for benign disease. J Low Genit Tract Dis. 2003;7:194–202.

 PubMedGoogle Scholar

Chesson HW, Ekwueme DU, Saraiya M, Watson M, Lowy DR, Markowitz LE. Estimates of the annual direct medical costs of the prevention and treatment of disease associated with human papillomavirus in the United States. Vaccine. 2012;30(42):6016–19. doi:10.1016/j.vaccine.2012.07.056.

 PubMed Web of Science ®Google Scholar

Goldie SJ, Kim JJ, Wright TC. Cost-effectiveness of human papillomavirus DNA testing for cervical cancer screening in women aged 30 years or more. Obstet Gynecol. 2004;103(4):619–31.

 Google Scholar