Penile cancer: a Brazilian consensus statement for low- and middle-income countries.

PURPOSE: Penile cancer is highly prevalent in low- and middle-income countries, with significant morbidity and mortality rates. The first Brazilian consensus provides support to improve penile cancer patients' outcomes, based on expert's opinion and evidence from medical literature. METHODS: Fifty-one Brazilian experts (clinical oncologists, radiation oncologists, urologists, and pathologists) assembled and voted 104 multiple-choice questions, confronted the results with the literature, and ranked the levels of evidence. RESULTS: Healthcare professionals need to deliver more effective communication about the risk factors for penile cancer. Staging and follow-up of patients include physical examination, computed tomography, and magnetic resonance imaging. Close monitoring is crucial, because most recurrences occur in the first 2-5 years. Lymph-node involvement is the most important predictive factor for survival, and management depends on the location (inguinal or pelvic) and the number of lymph nodes involved. Conservative treatment may be helpful in selected patients without compromising oncological outcomes; however, surgery yields the lowest rate of local recurrence. CONCLUSION: This consensus provides an essential decision-making orientation regarding this challenging disease.

Incidence, cost and gender differences of oropharyngeal and noncervical anogenital cancers in South Korea.

BACKGROUND: Human papillomavirus (HPV) is associated with a significant public health burden, yet few studies have been conducted in Asia, especially on noncervical cancers. We estimated the incidence and cost of oropharyngeal and noncervical anogenital (anal, vulvar, vaginal, penile) cancer in Korea. METHODS: We conducted a retrospective cohort study using Korea's National Health Insurance (NHI) claim database from 2013 to 2016. The main outcome measures were the number of respective cancer incidences during the study period and the annual costs per patient in the first year after diagnosis, which was adjusted by relevant variables based on the regression analysis. RESULTS: During the study period, 8022 patients with these cancers were identified, and oropharyngeal cancer comprised 46% of them. The crude incidence rate for male oropharyngeal cancer was significantly higher than that of females (3.1 vs. 0.7 per 100,000 as of 2016, respectively). Additionally, the crude incidence of male oropharyngeal cancer increased from 2.7 in 2013 to 3.1 in 2016, whereas that of female and other cancers was stable during the study period. The mean annual incidence-based cost per patient in 2016 was highest for oropharyngeal cancers (21,870 USD), and it was significantly higher in males than in females based on then regression analysis (p < .001). CONCLUSIONS: Oropharyngeal cancer comprises the highest number of HPV-associated noncervical cancer incidences in Korea, and the incidence and cost of oropharyngeal cancer was significantly higher among males than females. More aggressive public health policy toward males may decrease gender gap of oropharyngeal cancer.

Systematic review and evidence synthesis of non-cervical human papillomavirus-related disease health system costs and quality of life estimates.

BACKGROUND: Many economic evaluations of human papillomavirus vaccination should ideally consider multiple disease outcomes, including anogenital warts, respiratory papillomatosis and non-cervical cancers (eg, anal, oropharyngeal, penile, vulvar and vaginal cancers). However, published economic evaluations largely relied on estimates from single studies or informal rapid literature reviews. METHODS: We conducted a systematic review of articles up to June 2016 to identify costs and utility estimates admissible for an economic evaluation from a single-payer healthcare provider's perspective. Meta-analyses were performed for studies that used same utility elicitation tools for similar diseases. Costs were adjusted to 2016/2017 US$. RESULTS: Sixty-one papers (35 costs; 24 utilities; 2 costs and utilities) were selected from 10 742 initial records. Cost per case ranges were US$124-US$883 (anogenital warts), US$6912-US$52 579 (head and neck cancers), US$12 936-US$51 571 (anal cancer), US$17 524-34 258 (vaginal cancer), US$14 686-US$28 502 (vulvar cancer) and US$9975-US$27 629 (penile cancer). The total cost for 14 adult patients with recurrent respiratory papillomatosis was US$137 601 (one paper).Utility per warts episode ranged from 0.651 to 1 (12 papers, various utility elicitation methods), with pooled mean EQ-5D and EQ-VAS of 0.86 (95% CI 0.85 to 0.87) and 0.74 (95% CI 0.74 to 0.75), respectively. Fifteen papers reported utilities in head and neck cancers with range 0.29 (95% CI 0.0 to 0.76) to 0.94 (95% CI 0.3 to 1.0). Mean utility reported ranged from 0.5 (95% CI 0.4 to 0.61) to 0.65 (95% CI 0.45 to 0.75) (anal cancer), 0.59 (95% CI 0.54 to 0.64) (vaginal cancer), 0.65 (95% CI 0.60 to 0.70) (vulvar cancer) and 0.79 (95% CI 0.74 to 0.84) (penile cancer). CONCLUSIONS: Differences in values reported from each paper reflect variations in cancer site, disease stages, study population, treatment modality/setting and utility elicitation methods used. As patient management changes over time, corresponding effects on both costs and utility need to be considered to ensure health economic assumptions are up-to-date and closely reflect the case mix of patients.

Mean treatment cost of incident cases of penile cancer for privately insured patients in the United States.

PURPOSE: The aims of this study were to estimate the short-term cost of treating newly diagnosed penile cancer and determine the correlates of penile cancer treatment cost in the United States. METHODS: The Truven MarketScan database was used to identify commercially insured patients with penile cancer newly diagnosed during 2011 to 2014. A control group without HPV-related cancer diagnosis was selected by matching to the case group by the propensity score method. Total healthcare costs in the 2 years after the cancer diagnosis index date were measured for each patient. The mean difference between case and control groups was considered the cancer-related cost. For patients without complete 2-year data, a generalized linear regression was performed to predict cost for censored months and identify predictors associated with monthly cost. RESULTS: A total of 250 patients with newly diagnosed penile cancer and 250 matched controls were included in the study. The adjusted mean differential healthcare cost for penile cancer was $76,404 in the first 2 years. For the penile cancer group, cost peaked in month 1 at $10,202 and dropped substantially each month thereafter until month 7, when the cost was $4,295. After month 7, the monthly cost remained steady at $2,700 to $4,200. CONCLUSIONS: The estimated average cost of penile cancer for insured patients in the United States was about $76,000 in the first 2 years after diagnosis. Monthly cost was directly related to age, length of follow-up, comorbidity score, and prediagnosis cost.

Hospitalizations associated with malignant neoplasia and in situ carcinoma in the anus and penis in men and women during a 5-year period (2009-2013) in Spain: An epidemiological study.

BACKGROUND: Approximately 40,000 new cases of anal cancer and 26,000 new cases of penile cancer occurred in 2012 worldwide. Human Papillomavirus (HPV) infection is responsible for 88.3% and 33.0% of these cancers, respectively. The aim of this study was to describe the hospital burden associated with malignant neoplasm (MN) and in situ carcinoma (ISC) in the anus and penis in Spain from 2009 to 2013. METHODS: This observational, retrospective study used discharge information obtained from the national surveillance system for hospital data, Conjunto Mínimo Básico de Datos, provided by the Ministry of Health. RESULTS: We found 3,668 hospitalizations due to MN and ISC in the anus for both genders, and more than 55% of these hospitalizations occurred in men and were associated with a lower median age of hospitalization (p < 0.001), higher average length of hospital stay (ALOS) (p = 0.0032), higher hospitalization costs (p < 0.001) and higher hospitalization rate (2.141 per 100,000 males aged > 14 y old and 1.604 per 100,000 women aged > 14 y old, p < 0.001) than in women. During the same period, 4,156 hospitalizations due to MN and ISC of the penis were registered. The hospitalization rate was 4.320 per 100,000 males aged > 14 y old. The hospitalization rate due to MN and ISC in the anus in males increased significantly during this period (p = 0.048). CONCLUSION: Our study provides relevant information about the hospital burden of anal and penile MN and ISC in Spain. This information could be useful for cost effectiveness analysis of universal HPV vaccination and for future HPV vaccination impact monitoring in Spain, and for other countries of similar socioeconomic status.

The economic burden of human papillomavirus-related precancers and cancers in Sweden.

BACKGROUND: High-risk (HR) human papillomavirus (HPV) infection is an established cause of malignant disease. We used a societal perspective to estimate the cost of HR HPV-related cervical, vulvar, vaginal, anal, and penile precancer and cancer, and oropharyngeal cancer in Sweden in 2006, 1 year before HPV vaccination became available in the country. MATERIALS AND METHODS: This prevalence-based cost-of-illness study used diagnosis-specific data from national registries to determine the number of HR HPV-related precancers and cancers. The HR HPV-attributable fractions of these diseases were derived from a literature review and applied to the total burden to estimate HR HPV-attributable costs. Direct costs were based on health care utilization and indirect costs on loss of productivity due to morbidity (i.e., sick leave and early retirement) and premature mortality. RESULTS: The total annual cost of all HR HPV-attributable precancers and cancers was €94 million (€10.3/inhabitant). Direct costs accounted for €31.3 million (€3.4/inhabitant) of the total annual cost, and inpatient care amounted to €20.7 million of direct costs. Indirect costs made up €62.6 million (€6.9/inhabitant) of the total annual cost, and premature mortality amounted to €36 million of indirect costs. Cervical precancer and cancer was most costly (total annual cost €58.4 million). Among cancers affecting both genders, anal precancer and cancer, and oropharyngeal cancer were the most costly (€11.2 million and €11.9 million, respectively). For oropharyngeal cancer, males had the highest health care utilization and represented 71% of the total annual cost. Penile precancer and cancer was least costly (€2.6 million). CONCLUSION: The economic burden of HR HPV-related precancers and cancers is substantial. The disease-related management and treatment costs we report are relevant as a point of reference for future economic evaluations investigating the overall benefits of HPV vaccination in females and males in Sweden.

Estimating the cost-effectiveness profile of a universal vaccination programme with a nine-valent HPV vaccine in Austria.

BACKGROUND: HPV is a major cancer-causing factor in both sexes in the cervix, vulva, vagina, anus, penis, oropharynx as well as the causal factor in other diseases such as genital warts and recurrent respiratory papillomatis. In the context of the arrival of a nonavalent HPV vaccine (6/11/16/18/31/33/45/52/58), this analysis aims to estimate the public health impact and the incremental cost-effectiveness of a universal (girls and boys) vaccination program with a nonavalent HPV vaccine as compared to the current universal vaccination program with a quadrivalent HPV vaccine (6/11/16/18), in Austria. METHOD: A dynamic transmission model including a wide range of health and cost outcomes related to cervical, anal, vulvar, vaginal diseases and genital warts was calibrated to Austrian epidemiological data. The clinical impact due to the 5 new types was included for cervical and anal diseases outcomes only. In the base case, a two-dose schedule, lifelong vaccine type-specific protection and a vaccination coverage rate of 60% and 40% for girls and boys respectively for the 9-year old cohorts were assumed. A cost-effectiveness threshold of €30,000/QALY-gained was considered. RESULTS: Universal vaccination with the nonavalent vaccine was shown to reduce the incidence of HPV16/18/31/33/45/52/58 -related cervical cancer by 92%, the related CIN2/3 cases by 96% and anal cancer by 83% and 76% respectively in females and males after 100 years, relative to 75%, 76%, 80% and 74% with the quadrivalent vaccine, respectively. Furthermore, the nonavalent vaccine was projected to prevent an additional 14,893 cases of CIN2/3 and 2544 cases of cervical cancer, over 100 years. Depending on the vaccine price, the strategy was shown to be from cost-saving to cost-effective. CONCLUSION: The present evaluation showed that vaccinating 60% of girls and 40% of boys aged 9 in Austria with a 9-valent vaccine will substantially reduce the incidence of cervical cancer, CIN and anal cancer compared to the existing strategy. The vaccination strategies performed with the 9-valent vaccine in the current study were all found to be cost-effective compared to the current quadrivalent vaccination strategy by considering a cost-effectiveness threshold of 30,000€/QALY gained.

Racial and economic disparities in the treatment of penile squamous cell carcinoma: Results from the National Cancer Database.

PURPOSE: We evaluated sociodemographic and economic differences in overall survival (OS) of patients with penile SCC using the National Cancer Data Base (NCDB). METHODS: We identified 5,412 patients with a diagnosis of penile squamous cell carcinoma from 1998 to 2011 with clinically nonmetastatic disease and available pathologic tumor and nodal staging. OS was estimated using the Kaplan-Meier method, and differences were determined using the log-rank test. Cox proportional hazard regression was performed to identify independent predictors of OS. RESULTS: Estimated median OS was 91.9 months (interquartile range: 25.8-not reached) at median follow-up of 44.7 months (interquartile range: 17.2-81.0). Survival did not change over the study period (P = 0.28). Black patients presented with a higher stage of disease (pT3/T4: 16.6 vs. 13.2%, P = 0.027) and had worse median OS (68.6 vs. 93.7 months, P<0.01). Patients with private insurance and median income≥$63,000 based on zip code presented with a lower stage of disease (pT3/T4: 11.6 vs. 14.7%, P = 0.002 and 12.0 vs. 14.0%, P = 0.042, respectively) and had better median OS (163.2 vs. 70.8 months, P<0.01 and 105.3 vs. 86.4 months, p = 0.001, respectively). On multivariate analysis, black race (hazard ratio [HR]: 1.39, 95% confidence interval [CI]: 1.21-1.58; P<0.01) was independently associated with worse OS, whereas private insurance (HR = 0.79, 95% CI: 0.63-0.98; P = 0.028) and higher median income≥$63,000 (HR = 0.82; 95% CI: 0.72-0.93; P = 0.001) were independently associated with better OS. CONCLUSIONS: Racial and economic differences in the survival of patients with penile cancer exist. An understanding of these differences may help minimize disparities in cancer care.

Penile cancer treatment costs in England.

BACKGROUND: Penile cancer is a rare malignancy in Western countries, with an incidence rate of around 1 per 100,000. Due to its rarity, most treatment recommendations are based on small trials and case series reports. Furthermore, data on the resource implications are scarce. The objective of this study was to estimate the annual economic burden of treating penile cancer in England between 2006 and 2011 and the cost of treating a single case based on a modified version of the European Association of Urology penile cancer treatment guidelines. METHODS: A retrospective (non-comparative) case series was performed using data extracted from Hospital Episode Statistics. Patient admission data for invasive penile cancer or carcinoma in situ of the penis was extracted by ICD-10 code and matched to data from the 2010/11 National Tariff to calculate the mean number of patients and associated annual cost. A mathematical model was simultaneously developed to estimate mean treatment costs per patient based on interventions and their associated outcomes, advised under a modified version of the European Association of Urologists Treatment Guidelines. RESULTS: Approximately 640 patients per year received some form of inpatient care between 2006 and 2011, amounting to an average of 1,292 spells of care; with an average of 48 patients being treated in an outpatient setting. Mean annual costs per invasive penile cancer inpatient and outpatient were £3,737 and £1,051 respectively, with total mean annual costs amounting to £2,442,020 (excluding high cost drugs). The mean cost per case, including follow-up, was estimated to be £7,421 to £8,063. Results were sensitive to the setting in which care was delivered. CONCLUSIONS: The treatment of penile cancer consumes similar levels of resource to other urological cancers. This should be factored in to decisions concerning new treatment modalities as well as choices around resource allocation in specialist treatment centres and the value of preventative measures.

Incidence and cost of anal, penile, vaginal and vulvar cancer in Denmark.

BACKGROUND: Besides being a causative agent for genital warts and cervical cancer, human papillomavirus (HPV) contributes to 40-85% of cases of anal, penile, vaginal and vulvar cancer and precancerous lesions. HPV types 16 & 18 in particular contribute to 74-93% of these cases. Overall the number of new cases of these four cancers may be relatively high implying notable health care cost to society. The aim of this study was to estimate the incidence and the health care sector costs of anal, penile, vaginal and vulvar cancer. METHODS: New anogenital cancer patients were identified from the Danish National Cancer Register using ICD-10 diagnosis codes. Resource use in the health care sector was estimated for the year prior to diagnosis, and for the first, second and third years after diagnosis. Hospital resource use was defined in terms of registered hospital contacts, using DRG (Diagnosis Related Groups) and DAGS (Danish Outpatient Groups System) charges as cost estimates for inpatient and outpatient contacts, respectively. Health care consumption by cancer patients diagnosed in 2004-2007 was compared with that by an age- and sex-matched cohort without cancer. Hospital costs attributable to four anogenital cancers were estimated using regression analysis. RESULTS: The annual incidence of anal cancer in Denmark is 1.9 per 100,000 persons. The corresponding incidence rates for penile, vaginal and vulvar cancer are 1.7, 0.9 and 3.6 per 100,000 males/females, respectively. The total number of new cases of these four cancers in Denmark is about 270 per year. In comparison, the total number of new cases cervical cancer is around 390 per year. The total cost of anogenital cancer to the hospital sector was estimated to be 7.6 million Euros per year. Costs associated with anal and vulvar cancer constituted the majority of the costs. CONCLUSIONS: Anogenital cancer incurs considerable costs to the Danish hospital sector. It is expected that the current HPV vaccination program will markedly reduce this burden.

Should male circumcision be advocated for genital cancer prevention?

The recent policy statement by the Cancer Council of Australia on infant circumcision and cancer prevention and the announcement that the quadrivalent human papillomavirus (HPV) vaccine will be made available for boys in Australia prompted us to provide an assessment of genital cancer prevention. While HPV vaccination of boys should help reduce anal cancer in homosexual men and cervical cancer in women, it will have little or no impact on penile or prostate cancer. Male circumcision can reduce cervical, penile and possibly prostate cancer. Promotion of both HPV vaccination and male circumcision will synergistically maximize genital cancer prevention.

Years of potential life lost and productivity costs because of cancer mortality and for specific cancer sites where human papillomavirus may be a risk factor for carcinogenesis-United States, 2003.

BACKGROUND: Although years of potential life lost (YPLL) and mortality-related productivity costs comprise a substantial portion of the burden of cancers where human papillomavirus (HPV) may be a risk factor for carcinogenesis (called HPV-associated cancers in this report), estimates of these costs are limited. The authors estimated the mortality-related burden (in terms of YPLL and productivity costs) of HPV-associated cancers (without regard to the percentage of each of these cancers that could be attributed to HPV) and all malignant cancers in the United States in 2003. METHODS: The authors used 2003 national mortality data and US life tables to estimate YPLL for HPV-associated cancers and all malignant cancers. YPLL was estimated by using the life expectancy method. The human capital approach was used to estimate the value of the expected future lifetime productivity losses caused by premature deaths from HPV-associated cancers and all malignant cancers. Indirect mortality costs were estimated as the product of the number of deaths and the expected value of individuals' future earnings, including an imputed value of housekeeping services. RESULTS: In 2003, HPV-associated cancers accounted for 181,026 YPLL, which represented 2.4% of the estimated 7.5 million YPLL attributable to all malignant cancers in the United States. The average number of YPLL was 21.8 per HPV-associated cancer death and 16.3 per death from overall malignant cancers. Overall, HPV-associated cancers had the largest relative contribution to YPLL in women ages 30 to 34 years. The lifetime productivity cost from mortality in 2003 was $3.7 billion for HPV-associated cancer mortality and $133.5 billion for overall malignant cancer mortality. CONCLUSIONS: HPV-associated cancers impose a considerable burden in terms of premature deaths and productivity losses.

The economic burden of noncervical human papillomavirus disease in the United States.

OBJECTIVE: The purpose of this study was (1) to estimate the direct medical costs of 7 major noncervical human papillomavirus (HPV)-related conditions that include genital cancers, mouth and oropharyngeal cancers, anogenital warts, and juvenile-onset recurrent respiratory papillomatosis, and (2) to approximate the economic burden of noncervical HPV disease. STUDY DESIGN: For each condition, we synthesized the best available secondary data to produce lifetime cost per case estimates, which were expressed in present value. Using an incidence-based approach, we then applied these costs to develop an aggregate measure of economic burden. RESULTS: The economic burden that was associated with noncervical HPV-6-, -11-, -16-, and -18-related conditions in the US population in the year 2003 approximates $418 million (range, $160 million to $1.6 billion). CONCLUSION: The economic burden of noncervical HPV disease is substantial. Analyses that assess the value of investments in HPV prevention and control programs should take into account the costs and morbidity and mortality rates that are associated with these conditions.

Neonatal circumcision revisited. Fetus and Newborn Committee, Canadian Paediatric Society.

OBJECTIVE: To assist physicians in providing guidance to parents regarding neonatal circumcision. OPTIONS: Whether to recommend the routine circumcision of newborn male infants. OUTCOMES: Costs and complications of neonatal circumcision, the incidence of urinary tract infections, sexually transmitted diseases and cancer of the penis in circumcised and uncircumcised males, and of cervical cancer in their partners, and the costs of treating these diseases. EVIDENCE: The literature on circumcision was reviewed by the Fetus and Newborn Committee of the Canadian Paediatric Society. During extensive discussion at meetings of the committee over a 24-month period, the strength of the evidence was carefully weighed and the perspective of the committee developed. VALUES: The literature was assessed to determine whether neonatal circumcision improves the health of boys and men and is a cost-effective approach to preventing penile problems and associated urinary tract conditions. Religious and personal values were not included in the assessment. BENEFITS, HARMS AND COSTS: The effect of neonatal circumcision on the incidence of urinary tract infection, sexually transmitted diseases, cancer of the penis, cervical cancer and penile problems; the complications of circumcision; and estimates of the costs of neonatal circumcision and of the treatment of later penile conditions, urinary tract infections and complications of circumcision. RECOMMENDATION: Circumcision of newborns should not be routinely performed. VALIDATION: This recommendation is in keeping with previous statements on neonatal circumcision by the Canadian Paediatric Society and the American Academy of Pediatrics. The statement was reviewed by the Infectious Disease Committee of the Canadian Paediatric Society. The Board of Directors of the Canadian Paediatric Society has reviewed its content and approved it for publication. SPONSOR: This is an official statement of the Canadian Paediatric Society. No external financial support has been received by the Canadian Paediatric Society, or its members, for any portion of the statement's preparation.

Routine neonatal circumcision: a cost-utility analysis.

A cost-utility analysis was performed to evaluate the relative importance of each of the various elements in the current circumcision debate. Elements used in the analysis included the cost of the procedure, the pain associated with the procedure, the risk of urinary tract infections, and the risk of penile cancer. The net, discounted lifetime dollar cost of routine circumcision is $102 per person, while the net, discounted lifetime health cost is 14 hours of healthy life. These results suggest that the financial and medical advantages and disadvantages of routine neonatal circumcision cancel each other and that factors other than cost or health outcomes must be used in decision making.