Economic burden of non-cervical cancers attributable to human papillomavirus: a European scoping review

Figures & data

Figure 1. Results of the literature search and evaluation of identified studies. Three conference abstracts are now published/accepted for publication62–64. EU, European Union; H&N, head and neck.

Table 1. Selected references by country and cancer type.

Reference	Country	Disease	Economic evaluation
Karnon et al.27	UK	Anal cancer	CEA, CUA
Czoski-Murray et al.28	UK	Anal cancer	CEA, CUA
Abramowitz et al.29	France	Anal cancer	COI
Rémy and Vainchtock30*	France	Penile cancer	COI
Rémy et al.31	France	Vulvar and vaginal cancers	COI
Mignogna et al.32	UK	H&N cancers	Not applicable (review)
Speight et al.33	UK	H&N cancers	CEA
Kim et al.34	UK	H&N cancers	COI
Selke et al.35	France	H&N cancers	Not applicable (review)
Kim et al.36*	France	H&N cancers	COI
Lacau St Guily et al.37	France	H&N cancers	COI
Ruff et al.38	Germany	H&N cancers	Not applicable (review)
van Agthoven et al.39	The Netherlands	H&N cancers	COI
Nijdam et al.40	The Netherlands	H&N cancers	COI
van Agthoven et al.41	The Netherlands	H&N cancers	COI
Zavras et al.42	Greece	H&N cancers	COI
Olsen43*†‡	Denmark	Anal, penile, vulvar, vaginal, H&N cancers	COI
Jit et al.44	UK	Cervical, anal, penile, vulvar, vaginal, H&N cancers, GW, RRP	CEA, CUA
Borget et al.45	France	Cervical, anal, penile, vulvar, vaginal, H&N cancers	COI
Rémy et al.46*§	Germany	Anal, H&N cancers	COI
Santana et al.47*	Portugal	Cervical, anal, penile, vulvar, vaginal, H&N cancers, GW	COI

CEA, cost-effectiveness analysis; COI, cost-of-illness; CUA, cost-utility analysis; GW, genital warts; H&N, head and neck; RRP, recurrent respiratory papillomatosis.

*Poster or oral presentation. † Full citation now available, Olsen J, et al. BMC Public Health 2012 (Dec 17);12:108262. ‡ Full citation now available, Olsen J, et al. Int J Otolaryngol Head Neck Surgery 2013; accepted for publication.71 § Full citations now available, Heitland W, et al. J Med Econ 2013;16(3):364–7163; Klussmann JP, et al. ClinicoEconom Outcomes Res 2013; accepted for publication64.

Table 2. Overview of health economic references for anal cancer.

Reference	Country	Costing year	Study design	Key cost data*
Published papers
Karnon et al.27	UK	2007	Cost-utility analysis of screening for anal cancer. Cohort-based Markov model to represent the natural history of anal cancer and human immunodeficiency (HIV) infection in men who have sex with men (MSM).	Lifetime treatment costs per patient, mean (range): ▪ Screen-detected anal cancer: £8895 (£6671–£11,119) ▪ Non-screen-detected anal cancer: £13,334 (£10,001–£16,668)
Czoski-Murray et al.28	UK	2007	Cost-utility analysis of screening for anal cancer. Decision-analytical models, incorporating national screening guideline criteria, to analyse the cost-effectiveness of screening in MSM who were HIV-positive or HIV-negative and women who were HIV positive.	Lifetime treatment costs per patient, mean: ▪ Screen-detected anal cancer: £8895 ▪ Non-screen detected anal cancer: £13,334
Abramowitz et al.29	France	2007	Cost-of-illness study in men and women hospitalized with anal cancer in 2006. Retrospective analysis of data from a French national hospital database.	Total annual cost of management: ▪ Mean per patient (public sector: €6228; private sector: €4695) ▪ €38.2 million (€20.3 million hospital costs, €12.0 million outpatient costs, €5.97 million indirect costs) ▪ HPV-related anal cancer (88% of anal cancers attributable to HPV): €33.7 million
Borget et al.45	France	2007	Report based on the study of Abramowitz et al.29 presented above.	Mean (SD) annual hospitalization cost per patient: ▪ €5478 (5081) Total annual cost of management: ▪ €38.2 million (€20.3 million hospital costs, €12.0 million outpatient costs, €6.0 million indirect costs) ▪ HPV-related anal cancer: €32.2 million (females: €22.2 million; males: €10.0 million)
Jit et al.44	UK	2008–2009	Cost utility/cost-effectiveness study using a transmission dynamic model of HPV transmission and disease to compare bivalent and quadrivalent HPV vaccines.	Lifetime treatment cost per patient: ▪ £13,050
Conference communications
Rémy et al.46^‡	Germany	Not stated; study year 2008	Retrospective cost-of-illness study based on hospitalization, inpatient rehabilitation, and sick leave data from five German public databases.	Total annual cost of management: ▪ €34.1 million (€29.5 million hospitalization costs, €1.3 million inpatient rehabilitation, €3.3 million sick leave) ▪ HPV-related anal cancer (84.2% of anal cancers attributable to HPV): €28.7 million (females: €17.7 million; males: €10.9 million)
Olsen43^†	Denmark	2008	Retrospective, longitudinal cost-of-illness study based on estimated healthcare resource use for new patients identified from the Danish National Cancer Registry.	Mean annual healthcare cost per patient: (0) cost the year before time of diagnosis, (1) cost 1st year, (2) cost 2nd year, (3) cost 3rd year (95% CI): ▪ (0) €4285 (€3260–€5612); (1) €23,557 (€18,298–€30,323); (2) €7926 (€6119–€10,265); (3) €5753 (€4266–€7750) Total healthcare cost: ▪ Per patient: €40,961 ▪ Per year in Denmark: €4.28 million ▪ Per year in Denmark attributable to HPV 16/18: €3.36 million
Santana et al.47	Portugal	2009	Retrospective cost-of-illness study using data from Portuguese databases.	Total healthcare cost (HPV-related cases): ▪ Per patient: €7554 ▪ Per year in Portugal (all HPV types): €3.91 million ▪ Per year in Portugal (HPV 6/11/16/18): €2.59 million

HPV, human papillomavirus.

*Some totals may not be the exact sum of the component values due to the effects of rounding up/down. †Full citation now available, Olsen J, et al. BMC Public Health 2012 (Dec 17); 12:108262. ‡Full citation now available, Heitland W, et al. J Med Econ 2013;16(3):364–7163.

Table 3. Overview of health economic references for head and neck cancers.

Reference	Country	Costing year	Anatomical sites	Time horizon	Perspective	Key cost data*
Published papers
van Agthoven et al.39	The Netherlands	1996	Larynx, oral cavity, oropharynx	10 years	Hospital	Average direct healthcare costs (discounted) per patient: ▪ €31,829 (primary tumour: €21,581; recurrent  tumour: €9825; long-term follow-up: €423)
Zavras et al.42	Greece	2001	Oral cavity	3 years	Hospital	Mean direct healthcare costs per patient: ▪ €8450 (stage I: €3815; stage II: €6112; stage III:  €10,780; stage IV: €11,950)
Nijdam et al.40	The Netherlands	2001	Oropharynx	5 years	Hospital	Mean direct healthcare costs per patient (weighted by number of patients for each treatment modality): ▪ Brachytherapy: €18,001 ▪ Surgery: €28,130 ▪ External beam radiation therapy: €21,143
Speight et al.33	UK	2002–2003	Oral cavity, oropharynx, pharynx	3 years	NHS	Mean direct healthcare cost per patient: ▪ £1869 (pre-cancer); £4914 (stage I); £8535 (stage II);  £11,883 (stage III); £13,513 (stage IV)
van Agthoven et al.41	The Netherlands	2003	Larynx	1 year	Hospital	Mean direct healthcare costs per patient: ▪ Diagnostic phase: €3207 ▪ Treatment phase: dysplasia (€3169); carcinoma in  situ (€5026); T1 stage (€6458); T2 stage (€8037); T3  stage (€12,765); T4 stage (€19,227) ▪ Disease-free follow-up (1 year): €1856
Lacau St Guily et al.37	France	2008	Larynx, oral cavity, oropharynx, pharynx, salivary glands	1 year	Healthcare payer	Mean total annual cost per patient: ▪ €14,629 Total annual cost of management: ▪ €530 million (€323 million hospital costs, €131  million outpatient costs, €76 million indirect costs) ▪ HPV-related head and neck cancers (26% of head and  neck cancers attributable to HPV): €138 million
Borget et al.45 (report based on data from Lacau St Guily et al.37)	France	2008	Larynx, oral cavity, oropharynx, pharynx	1 year	Healthcare payer	Mean annual hospitalization cost per patient: ▪ Larynx (€5599); oral cavity (€6634); oropharynx  (€6819); pharynx (€6838) Total annual cost of management: ▪ €475 million (€275 million hospital costs, €127  million outpatient costs, €74 million indirect costs)  HPV-related head and neck cancers: €113 million  (females: €18.0 million; males: €94.6 million)
Kim et al.34	UK	2003–2009	Head and neck	5 years	Hospital	Mean cost of post-operative healthcare utilization was £23,212 over 5 years ▪ Inpatient care cost: £21,978 ▪ Outpatient care cost: £1,233 Total cost of post-operative healthcare utilization was estimated to be £255.5 million over 5 years
Jit et al.44	UK	2008–2009	Oropharynx	Lifetime	Healthcare payer	Lifetime treatment cost per patient: ▪ £15,000
Ruff et al.38	Germany	Not applicable (review)	Larynx, oral cavity, pharynx	1 year	Not applicable (review)	Total annual smoking-attributable direct and indirect costs: ▪ Oral cavity and pharyngeal cancer: €771 million  (direct healthcare costs: €124 million) ▪ Laryngeal cancer: €226 million (direct healthcare  costs: €47 million)
Selke et al.35	France	Not applicable (review)	Head and neck	1 year	Not applicable (review)	Total annual hospital treatment costs: ▪ FF2.27 billion
Mignogna et al.32	UK	Not applicable (review)	Oral cavity, oropharynx	1 year	Not applicable (review)	Total cost of inpatient stays for oral cancer in England in 1993: ▪ £8 million Cost of surgical treatment of oropharyngeal cancer per patient in 1993: ▪ Early stage: £244 ▪ Late stage: £4800
Conference communications
Kim et al.36	France	2006–2008	Head and neck	2 years	Healthcare payer	Mean cost of inpatient postoperative healthcare per patient: ▪ 1st year: €6700; 2nd year: €3600 Mean total cost of post-operative healthcare per patient: ▪ 1st year: €14,500; 2nd year: €6800
Olsen43	Denmark	2008	Oral cavity, oropharynx, pharynx, salivary glands	3 years	Hospital	Total healthcare cost: ▪ Per patient: oral cavity (€34,270); oropharynx  (€40,005); pharynx (€44,500); salivary glands  (€26,332) ▪ Per year in Denmark: €28.08 million ▪ Per year in Denmark attributable to HPV 16/18: €5.81  million
Rémy et al.46^‡	Germany	Not stated; study year 2008	Head and neck	1 year	Society	Total annual cost of management: ▪ €366 million (€294 million hospitalization costs,  €13.1 million inpatient rehabilitation, €59.0 million  sick leave) ▪ HPV-related head and neck cancers (16.0–28.2% of  head and neck cancers attributable to HPV depending  on cancer type/location): €78.2 million (females:  €15.8 million; males: €62.4 million)
Santana et al.47	Portugal	2009	Head and neck	1 year	Hospital	Total healthcare cost (HPV-related cases): ▪ Per patient: €19,217 ▪ Per year in Portugal (all HPV types): €16.7 million ▪ Per year in Portugal (HPV 6/11/16/18): €3.81 million

HPV, human papillomavirus; NHS, National Health Service.

*Some totals may not be the exact sum of the component values due to the effects of rounding up/down. ‡Full citation now available, Klussmann JP, et al. ClinicoEconom Outcomes Res 2013; accepted for publication64.

Table 4. Anatomical sites for head and neck cancers represented in selected references.

Reference	Oral cavity	Oropharynx	Salivary glands	Pharynx	Larynx
Ruff et al.38	✓	✓	✓	✓	✓
Kim et al.34	✓	✓	×	✓	✓
Selke et al.35	✓	✓	×	✓	✓
van Agthoven et al.39	✓	✓	×	×	✓
Mignogna et al.32	✓	×	×	✓	×
Zavras et al.42	✓	×	×	×	×
Nijdam et al.40	×	✓	×	×	×
Speight et al.33	✓	✓	×	✓	×
van Agthoven et al.39	×	×	×	×	✓
Kim et al.36	✓	✓	×	✓	✓
Lacau St Guily et al.37	✓	✓	✓	✓	✓
Borget et al.45	✓	✓	×	✓	✓
Olsen43	✓	✓	✓	✓	×
Rémy et al.46^‡	✓	✓	×	✓	✓
Santana et al.47	✓	✓	×	✓	✓

‡Full citation now available, Klussmann JP, et al. ClinicoEconom Outcomes Res 2013; accepted for publication64.

Figure 2. Estimated annual hospital costs of cancers attributable to HPV in Denmark43, France45, and Portugal47 by type of cancer. Country (year): France (2006–2007); Denmark (2008); Portugal (2009). Burden approach: societal hospital economic burden; Perspective: hospital perspective; Type(s) of costs: hospital costs (attributable to HPV-16 &18); Analytical method: retrospective analysis of national hospital database or cancer registry (incident or prevalent patients); Time horizon: cross-sectional (yearly basis). H&N, head and neck; HPV, human papillomavirus.

Figure 3. Estimated annual total costs of HPV-related cancers attributable to HPV in males and females in France45. Reprinted from Borget I, Abramowitz L, Mathevet P. Economic burden of HPV-related cancers in France. Vaccine 2011;29:5245–9, with permission from Elsevier. Country (year): France (2006–2007). Burden approach: per-patient economic burden; Perspective: healthcare payer perspective; Type(s) of costs: hospital, outpatient, and daily allowance costs (attributable to HPV all types); Analytical method: retrospective analysis of national hospital database (prevalent patients); Time horizon: cross-sectional (yearly basis). H&N, head and neck; HPV, human papillomavirus.

Table A1. Keywords used for the literature search.

Anatomical area	Key words
Anus	Anal canal Anus neoplasms Anus diseases Anus neoplasms/economics
Penis	Penile abnormalities
Vulva	Vulvar neoplasms Vulvar diseases
Vagina	Vaginal abnormalities
Head and neck	Mouth neoplasms Oropharyngeal neoplasms Laryngeal neoplasms Tonsillar neoplasms Head and neck neoplasms Head and neck cancer
AND economics field	Cost Cost benefit analysis Costs and cost analysis

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