Patient-reported quality of life and symptom burden measures in human papillomavirus associated oropharyngeal cancer - A review of the literature and PRO methodology.

The emergence of human papillomavirus-associated oropharyngeal cancer (HPVOPC) has resulted in an explosion of clinical research offering reduced toxicity and improved health-related quality of life (HRQL) through treatment de-escalation. At the heart of this objective are patient-reported outcomes (PROs) which aim to quantify the patient experience, usually through the measurement of HRQL or symptom burden. A number of PRO measures (PROMs) are available to HNC researchers and selection of the optimal instrument relies on a detailed understanding of their content and psychometric properties matched to the clinical endpoint of interest. As PROMs become increasingly favoured as the primary or co-primary endpoints of interest in HNC clinical trials, particularly those focussed on HPVOPC, future treatment paradigms will be determined by these measures and it is imperative that they are applied with sophistication and rigor. This review draws attention to the limitations and challenges our specialty faces in PRO application, analysis and reporting. These shortfalls typically include a reliance on statistical rather than clinically relevant differences, multiple hypothesis testing, a lack of evidence-based minimal clinically important differences for the commonly used tools, as well as variations in PROM selection. The aim of this review is to provide: (1) an overview of PRO/PROM terminology and methodology in the HNC setting; (2) to provide a summary of HRQL and symptom burden reports in the HPVOPC literature; and (3) to draw attention to the unmet research need of refining PROM development, application and interpretation to guide our treatment decisions based on what matters to patients.

An economic and disease transmission model of human papillomavirus and oropharyngeal cancer in Texas.

In 2017, 46,157 and 3,127 new oropharyngeal cancer (OPC) cases were reported in the U.S. and Texas, respectively. About 70% of OPC were attributed to human papillomavirus (HPV). However, only 51% of U.S. and 43.5% of Texas adolescents have completed the HPV vaccine series. Therefore, modeling the demographic dynamics and transmission of HPV and OPC progression is needed for accurate estimation of the economic and epidemiological impacts of HPV vaccine in a geographic area. An age-structured population dynamic model was developed for the U.S. state of Texas. With Texas-specific model parameters calibrated, this model described the dynamics of HPV-associated OPC in Texas. Parameters for the Year 2010 were used as the initial values, and the prediction for Year 2012 was compared with the real age-specific incidence rates in 23 age groups for model validation. The validated model was applied to predict 100-year age-adjusted incidence rates. The public health benefits of HPV vaccine uptake were evaluated by computer simulation. Compared with current vaccination program, increasing vaccine uptake rates by 50% would decrease the cumulative cases by 4403, within 100 years. The incremental cost-effectiveness ratio of this strategy was $94,518 per quality-adjusted life year (QALY) gained. Increasing the vaccine uptake rate by 50% can: (i) reduce the incidence rates of OPC among both males and females; (ii) improve the quality-adjusted life years for both males and females; (iii) be cost-effective and has the potential to provide tremendous public health benefits in Texas.

Quality and Readability Assessment of Websites on Human Papillomavirus and Oropharyngeal Cancer.

OBJECTIVES/HYPOTHESIS: The incidence of human papillomavirus-positive (HPV+) oropharyngeal cancer is rising, but public knowledge about this diagnosis remains low. This study aimed to investigate the quality and readability of online information about HPV+ oropharyngeal cancer. STUDY DESIGN: Cross-sectional website analysis. METHODS: This study conducted a total of 12 web searches across Google, Yahoo, and Bing to identify websites related to HPV+ oropharyngeal cancer. The QUality Evaluation Scoring Tool (QUEST) was used to measure quality based on seven website criteria. The Flesch Reading Ease Score (FRES) and Flesch-Kincaid Grade Level (FKGL) were used to measure readability, with scores estimating the education level a reader would require to understand a piece of text. Readability improves as FRES increases and FKGL decreases. RESULTS: Twenty-seven unique web pages were evaluated. The mean USA reading grade level as measured by FKGL was 10.42 (standard deviation = 1.54). There was an inverse relationship between quality and readability, with a significant positive correlation between QUEST score and FKGL (r = 0.343, P = .040) and a significant negative correlation between QUEST score and FRES (r = -0.537, P = .002). CONCLUSIONS: With a mean USA reading grade level more than four grades above the American Medical Association's recommendation and results indicating that readability suffers as quality improves, these findings suggest that the currently available online information about HPV+ oropharyngeal cancer is insufficient. Improved patient education practices and resources about this diagnosis are needed. LEVEL OF EVIDENCE: NA Laryngoscope, 131:87-94, 2021.

Insurance Status as a Predictor of Treatment in Human Papillomavirus Positive Oropharyngeal Cancer.

OBJECTIVES: The link between human papillomavirus (HPV) and oropharyngeal cancer (OPC) is well known. Locally advanced, HPV-positive OPC (HPV OPC) can be treated with either chemoradiation or primary surgery with or without adjuvant therapy. Head and neck cancer patients with government insurance or uninsured have been shown to have worse prognosis than similar patients with private insurance. In this study, we aimed to determine if insurance status would predict treatment modality in patients with HPV OPC. STUDY DESIGN: A retrospective analysis using the National Cancer Database (NCDB). METHODS: The National Cancer Database was used to identify patients with HPV OPC who underwent primary surgery or primary chemoradiation from 2010-2015. Insurance status was categorized as government, private, or no insurance. The relationship between insurance status and treatment was investigated using Chi square and multivariate regression models. Kaplan-Meier analyses were performed comparing overall survival (OS) by insurance status. RESULTS: There were 10,606 patients were included. There was a statistically significant correlation between insurance status and primary treatment modality for HPV OPC (P < .001). Patients with government insurance were 19.3% less likely to undergo surgery and uninsured patients were 36.9% less likely to undergo primary surgery when compared to those with private insurance (P < .001), even after correcting for TNM stage in multivariate analysis. There was an improved 5-year OS for patients with private insurance (86.6%) versus both government insurance (68.4%) and no insurance (69.9%) (P < .001). CONCLUSIONS: Patients with private insurance are more likely to undergo primary surgery in HPV OPC and have improved overall survival. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:776-781, 2021.

Socioeconomic and Racial Disparities and Survival of Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVE: To investigate differences in epidemiology of oropharyngeal squamous cell carcinoma (OPSCC) with regards to human papillomavirus (HPV), race, and socioeconomic status (SES) using the National Cancer Database (NCDB). STUDY DESIGN: Population-based cohort study. SETTING: Racial and socioeconomic disparities in survival of OPSCC have been previously acknowledged. However, the distribution of HPV-related cancers and its influence on survival in conjunction with race and SES remain unclear. SUBJECTS AND METHODS: All patients with OPSCC in the NCDB with known HPV status from 2010 to 2016 were included. Differences in presentation, HPV status, treatment, and outcomes were compared along racial and socioeconomic lines. Univariable and multivariable Cox regression survival analyses were performed. RESULTS: In total, 45,940 patients met criteria. Most were male (38,038, 82.8%), older than 60 years (23,456, 51.5%), and white (40,156, 87.4%), and lived in higher median income areas (>$48,000, 28,587, 62.2%). Two-thirds were HPV positive (31,007, 67.5%). HPV-negative disease was significantly more common in lower SES (<$38,000, 2937, 41.5%, P < .001) and among blacks (1784, 55.3%, P < .001). Median follow-up was 33 months. Five-year overall survival was 81.3% (95% CI, 80.5%-82.1%) and 59.6% (95% CI, 58.2%-61.0%) in HPV-positive and HPV-negative groups, respectively. In univariable and multivariable analyses controlling for HPV status, age, stage, and treatment, black race (hazard ratio [HR], 1.22; 95% CI, 1.11-1.34; P < .001) and low SES (HR, 1.58; 95% CI, 1.45-1.72; P < .001) were associated with worse survival. CONCLUSION: Significant differences in HPV status exist between socioeconomic and racial groups, with HPV-negative disease more common among blacks and lower SES. When controlling for HPV status, race and SES still influence outcomes in oropharyngeal cancers.

Gender and race interact to influence survival disparities in head and neck cancer.

Gender and race disparities in head and neck squamous cell carcinoma (HSNCC) survival are independently well documented, but no prior studies have examined the joint effect of these factors on HSNCC outcomes. We aim to comprehensively estimate the effect of gender and race on overall survival in HNSCC. We constructed a retrospective cohort from the National Cancer Database for primary HNSCC of the larynx, hypopharynx, oral cavity, and oropharynx from 2010 to 2015. We used Kaplan-Meier curves and Cox proportional hazards regressions to calculate hazard ratios adjusting for treatment type, age, insurance, staging classifications, and comorbidities. Oral cavity cancer was significantly more common among Hispanic and White females compared to other sites. Female non-oropharyngeal HNSCC cases had better five-year overall survival than males (56.3% versus 54.4%, respectively), though Black females (52.8%) had poorer survival than both White (56.2%) and Hispanic (57.9%) males. There were significant differences in oropharyngeal cancer by HPV status. Notably, Black females with HPV-positive oropharyngeal OPSCC had far worse survival than any other race and gender group. These results persisted even when adjusting for potential mediating factors. Clearly gender is a significant prognosticator for HNSCC and has meaningful interactions with race. The distinct site distributions across gender and race reveal important insights into HNSCC among females. Taking into account these gender disparities while considering race is essential to providing appropriate care to head and neck patients and accurately counselling these individuals on prognosis and outcomes.

Costs of Definitive Chemoradiation, Surgery, and Adjuvant Radiation Versus De-Escalated Adjuvant Radiation per MC1273 in HPV+ Cancer of the Oropharynx.

PURPOSE: De-escalated treatment for human papillomavirus (HPV)+ oropharynx squamous cell carcinoma (OPSCC) has shown promising initial results. Health-care policy is increasingly focusing on high-value care. This analysis compares the cost of care for HPV+ OPSCC treated with definitive chemoradiation (CRT), surgery and adjuvant radiation (RT), and surgery and de-escalated CRT on MC1273. METHODS AND MATERIALS: MC1273 is a prospective, phase 2 study evaluating adjuvant CRT to 30 to 36 Gy plus docetaxel for HPV+ OPSCC after surgery for high-risk patients. Matched standard-of-care control groups were retrospectively identified for patients treated with definitive CRT or adjuvant RT. Standardized costs were evaluated before radiation, during treatment (during RT), and at short-term (6 month) and long-term (7-24 month) follow-up periods. RESULTS: A total of 56 definitive CRT, 101 adjuvant RT, and 66 MC1273 patients were included. The CRT arm had more T3-4 disease (63% vs 17-21%) and higher N2c-N3 disease (52% vs 20-24%) vs both other groups. The total treatment costs in the CRT, adjuvant RT, and MC1273 groups were $47,763 (standard deviation [SD], $19,060], $57,845 (SD, $17,480), and $46,007 (SD, $9019), respectively, and the chemotherapy and/or RT costs were $39,936 (SD, $18,480), $26,603 (SD, $12,542), and $17,864 (SD, $3288), respectively. The per-patient, per-month, average short-term follow-up costs were $3860 (SD, $10,525), $1072 (SD, $996), and $972 (SD, $833), respectively, and the long-term costs were $978 (SD, $2294), $485 (SD, $1156), and $653 (SD, $1107), respectively. After adjustment for age, T-stage, and N-stage, treatment costs remained lower for CRT and MC1273 versus adjuvant RT ($45,450 and $47,114 vs $58,590, respectively; P < .001), whereas the total per-patient, per-month follow-up costs were lower in the MC1273 study group and adjuvant RT versus CRT ($853 and $866 vs $2030, respectively; P = .03). CONCLUSIONS: MC1273 resulted in 10% and 20% reductions in global costs compared with standard-of-care adjuvant RT and definitive CRT treatments. Substantial cost savings may be an added benefit to the already noted low toxicity and maintained quality of life of treatment per MC1273.

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.

Considerations in Human Papillomavirus-Associated Oropharyngeal Cancer Screening: A Review.

Importance: The incidence of human papillomavirus (HPV)-positive oropharyngeal cancer (OPC) is anticipated to rise over the next few decades until the effects of prophylactic vaccination are realized, which highlights the potential importance of secondary prevention. The objective of this review is to evaluate the evidence associated with screening for HPV-positive OPC. Observations: Evaluation of a potential clinical preventive screening service requires characterization of the disease burden, the at-risk target screening population, screening tests, treatment, and screening benefits and harms. The lifetime risk of OPC is 0.7% for men and 0.2% for women and is expected to increase. The disease burden of HPV-positive OPC is substantial; most patients undergo morbid multimodality treatment and incur high costs in the process. Middle-aged and older adult men with elevated number of lifetime vaginal or oral sex partners are at highest risk. Patients may benefit from early detection of the disease-the 4-year overall survival of patients with stage I HPV-positive OPC is 87%, a considerable portion of whom are eligible for less morbid single-modality therapy. However, available screening tests are insufficiently sensitive and specific considering the current HPV-positive OPC incidence rates in the most at-risk patients. Further, the benefits and harms of screening for HPV-positive OPC are unknown. Conclusions and Relevance: The current and projected future population-level burden of HPV-positive OPC supports further exploration of secondary preventive interventions. However, screening for HPV-positive OPC is not currently justified. Advances in biomarker discovery and improved characterization of (1) a highly at-risk, target screening population and (2) the benefits and harms of screening will be necessary. Large-scale clinical trials and rigorous evaluation of how to best implement this service into clinical practice will also be needed.

Oral HPV prevalence assessment by Linear Array vs. SPF10 PCR-DEIA-LiPA25 system in the HPV Infection in Men (HIM) study.

INTRODUCTION: Oral human papillomavirus (HPV) attributable oropharyngeal cancers are on the rise in many countries. Oral HPV infections among healthy individuals are commonly detected using oral gargle samples. However, the optimal method for HPV genotyping oral gargle specimens in research studies has not been previously evaluated. MATERIALS AND METHODS: Oral gargle samples from 1455 HPV Infection in Men (HIM) study participants were HPV genotyped using two different methods: Linear Array and the SPF10 PCR-DEIA-LiPA25. The sensitivity of the two tests for detecting individual HPV types and grouped HPV types, high-risk HPV, low-risk HPV, grouped 4-HPV-vaccine types, and grouped 9-HPV-vaccine-types, and the degree of concordance between the two tests was assessed. We also examined whether socio-demographic-behavioral factors were associated with concordance between the two assays. RESULTS: The sensitivity of SPF10 PCR-DEIA-LiPA25 was higher than Linear Array, with the exception of HPV 70, for the detection of oral HPV. The prevalence ratio of SPF10 PCR-DEIA-LiPA25 to Linear Array varied between 1.0 and 9.0 for individual HPV genotypes, excluding HPV 70, and between 3.8 and 4.4 for grouped 4-valent and 9-valent HPV vaccine types, respectively. There was no association between socio-demographic-behavioral factors and discordance in results between the two tests for oral HPV 16 detection. DISCUSSION: SPF10 PCR-DEIA-LiPA25 was more sensitive than Linear Array for detecting HPV in oral gargle samples. Given the growing importance of detecting oral HPV infection for research studies of oral HPV natural history and vaccine effectiveness evaluation, we recommend using methods with higher sensitivity such as SPF10 PCR-DEIA-LiPA25 for detecting HPV in oral gargle samples.

Prognostic value of nodal involvement in patients with oropharyngeal carcinoma according to the HPV status. / Valoración de la capacidad pronóstica de la afectación ganglionar de los pacientes con carcinoma de orofaringe en función del estatus HPV.

BACKGROUND AND OBJECTIVE: Different studies performed in populations with a high incidence of HPV infection have found no prognostic capacity of clinical nodal involvement (cN+) in patients with HPV-positive oropharyngeal carcinomas. The objective of this study was to assess the prognostic ability of nodal involvement in patients with oropharyngeal carcinomas according to HPV status in a cancer population with a low incidence of HPV infection. MATERIAL AND METHODS: Retrospective study of a cohort of 420 patients with oropharyngeal carcinomas treated during the period 1990-2016 for whom information on HPV status was available. RESULTS: 14.8% of the patients included in the study had HPV-positive tumours. In relation to patients without nodal involvement (cN0), nodal involvement at diagnosis (cN+) significantly decreased the specific survival of patients with HPV-negative oropharyngeal carcinomas. Conversely, no differences in survival were found for patients with HPV-positive tumours according to the presence of nodal involvement. A history of toxic consumption did not change the absence of prognostic significance of nodal involvement for patients with HPV-positive tumours. CONCLUSIONS: Regional involvement at the time of diagnosis is not a prognostic variable for patients with HPV-positive oropharyngeal carcinomas.

Concurrent cisplatin or cetuximab with radiotherapy for HPV-positive oropharyngeal cancer: Medical resource use, costs, and quality-adjusted survival from the De-ESCALaTE HPV trial.

BACKGROUND: The De-ESCALaTE HPV trial confirmed the dominance of cisplatin over cetuximab for tumour control in patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC). Here, we present the analysis of health-related quality of life (HRQoL), resource use, and health care costs in the trial, as well as complete 2-year survival and recurrence. MATERIALS AND METHODS: Resource use and HRQoL data were collected at intervals from the baseline to 24 months post treatment (PT). Health care costs were estimated using UK-based unit costs. Missing data were imputed. Differences in mean EQ-5D-5L utility index and adjusted cumulative quality-adjusted life years (QALYs) were compared using the Wilcoxon signed-rank test and linear regression, respectively. Mean resource usage and costs were compared through two-sample t-tests. RESULTS: 334 patients were randomised to cisplatin (n = 166) or cetuximab (n = 168). Two-year overall survival (97·5% vs 90·0%, HR: 3.268 [95% CI 1·451 to 7·359], p = 0·0251) and recurrence rates (6·4% vs 16·0%, HR: 2·67 [1·38 to 5·15]; p = 0·0024) favoured cisplatin. No significant differences in EQ-5D-5L utility scores were detected at any time point. At 24 months PT, mean difference was 0·107 QALYs in favour of cisplatin (95% CI: 0·186 to 0·029, p = 0·007) driven by the mortality difference. Health care costs were similar across all categories except the procurement cost and delivery of the systemic agent, with cetuximab significantly more expensive than cisplatin (£7779 [P < 0.001]). Consequently, total costs at 24 months PT averaged £13517 (SE: £345) per patient for cisplatin and £21064 (SE: £400) for cetuximab (mean difference £7547 [95% CI: £6512 to £8582]). CONCLUSIONS: Cisplatin chemoradiotherapy provided more QALYs and was less costly than cetuximab bioradiotherapy, remaining standard of care for nonsurgical treatment of HPV-positive OPSCC.

Financial Vulnerability: A Case Study Involving a Patient With Head and Neck Cancer.

BACKGROUND: Patients with head and neck cancer (HNC) face unique financial challenges. Even with stable income and health insurance, many patients become overwhelmed with direct and indirect treatment-associated costs. OBJECTIVES: This article discusses how prolonged financial burden in patients with cancer can result in compromised patient outcomes. METHODS: A case study is presented that highlights financial burden associated with reduced income, treatment-related commuting, and challenges in resuming a job while dealing with functional impairments and long-term treatment effects from HNC. It also describes the financial impact on a spousal caregiver. FINDINGS: Nurses must initiate discussions with their patients about potential and actual financial concerns and barriers to care. In addition, nurses should include repeated assessment of financial health throughout the cancer care trajectory and provide appropriate resources and referrals when issues are identified.

Societal cost of oropharyngeal cancer by human papillomavirus status, cancer stage, and subsite.

BACKGROUND: The incidence of oropharyngeal cancer (OPC) is increasing, particularly human papillomavirus (HPV)-associated OPC. The aim of this study was to specify the total societal cost of OPC by HPV status, cancer stage, and subsite using a bottom-up cost-of-illness approach. METHODS: We analyzed 121 consecutive patients with OPC from the Southern Health Care Region of Sweden. We estimated the direct medical costs and indirect costs (e.g., disease-related morbidity and premature death) from 1 month prior to OPC diagnosis until 3 years after treatment completion. RESULTS: The mean total cost per patient was €103 386 for HPV-positive and €120 244 for HPV-negative OPC. Eighty-one percent of the patients analyzed were HPV-positive: Accordingly, HPV-positive OPC represented 79% of the total cost of OPC. The mean total cost of stage I, II, III, IVA, IVB, and IVC, regardless of HPV status, was €59 424, €57 000, €69 246, €115 770, €234 459, and €21 930, respectively, of which indirect costs were estimated at €22 493 (37.8%), €14 754 (25.9%), €28 681 (41.4%), €67 107 (58%), €166 280 (70.9%), and €0. Tonsillar cancer represented 64% of OPC, with a mean total cost of €117 512 per patient. CONCLUSION: The societal cost of OPC is substantial. HPV-associated OPC comprises 79% of the total cost of this disease. The data presented in this study may be used in analytical models to aid decision makers in determining the potential value of gender-neutral HPV vaccination.

HPV-related oropharyngeal cancer: a review on burden of the disease and opportunities for prevention and early detection.

The incidence of oropharyngeal cancer (OPC) related to infection with human papillomavirus (HPV) is rising, making it now the most common HPV-related malignancy in the United States. These tumors present differently than traditional mucosal head and neck cancers, and those affected often lack classic risk factors such as tobacco and alcohol use. Currently, there are no approved approaches for prevention and early detection of disease, thus leading many patients to present with advanced cancers requiring intense surgical or nonsurgical therapies resulting in significant side effects and cost to the health-care system. In this review, we outline the evolving epidemiology of HPV-related OPC. We also summarize the available evidence corresponding to HPV-related OPC prevention, including efficacy and safety of the HPV vaccine in preventing oral HPV infections. Finally, we describe emerging techniques for identifying and screening those who may be at high risk for developing these tumors.

Racial disparities and human papillomavirus status in oropharyngeal cancer: A systematic review and meta-analysis.

BACKGROUND: This study used a meta-analysis to quantify the degree to which the racial disparity in overall survival for black versus white Americans with oropharyngeal squamous cell carcinoma (OPSCC) persists after adjusting for human papillomavirus (HPV) status. METHODS: PubMed/MEDLINE, Cochrane Database of Systematic Reviews, and CINAHLA were searched through November 2017. The PRISMA statement was followed. The pooled hazard ratio (HR) was calculated using a random-effects model. RESULTS: Five studies met the inclusion criteria and had suitable data for pooling into the meta-analysis (N = 1153). The pooled HR for overall survival in black versus white Americans with OPSCC after adjusting for HPV status was calculated to be 1.45 (95% confidence interval, 0.87-2.40). CONCLUSIONS: The difference in survival for black versus white Americans with OPSCC is not significant after adjusting for HPV status but still trends in the direction of a disparity. Additional studies are needed to better characterize this disparity.

Epidemiological dynamic modeling of human papillomavirus-related diseases to assess vaccination strategies in Argentina.

Our objective was to develop and test a dynamic simulation model of human papillomavirus (HPV)-related diseases to assess rational vaccination strategies in Argentina. A dynamic stochastic transmission model for hetero- and homosexual transmission of HPV oncogenic and low-risk oncogenic types among females and males was developed. The model included HPV transmission and vaccination, the natural history of HPV-related diseases, disease outcomes, and cervical cancer screening. Considering all cervical cancers, covered or not by the current quadrivalent vaccine, the existing coverage rate would lead to 60% reduction in the global incidence of cervical cancer at 25 years, and to 79% at 50 years. Isolated current female vaccination without a screening program would need around 100 years to eliminate cervical cancer from the local population. Current coverage rate would lead to 59% reduction of vulvar cancer, 76% of vaginal cancer, 85% of anal cancer, and 87% of oropharyngeal cancer, estimated over a 25-year time prospect. Female HPV vaccination within the context of current cervical cancer screening should reach a minimum long-term mean coverage of 60% of girls, receiving at least a two-dose vaccine schedule, to significantly reduce or virtually eliminate cervical cancer at 50 years. Including vaccination to boys to improve herd immunity did not influence the incidence of cervical cancer over time, as long as female coverage did not fall below 50%. Regarding vulvar, vaginal, anal, penile, and some oropharyngeal cancers, current girls-only based vaccination could virtually eliminate these cancer types after 35-40 years, both in women and men.

Cost-Effectiveness Analysis of Intensity Modulated Radiation Therapy Versus Proton Therapy for Oropharyngeal Squamous Cell Carcinoma.

PURPOSE: To compared the cost-effectiveness of intensity modulated proton beam therapy (PBT) and intensity modulated radiation therapy (IMRT) in the management of stage III-IVB oropharynx cancer (OPC). METHODS AND MATERIALS: A Markov model was constructed to compare IMRT with PBT for a 65-year-old patient with stage IVA OPSCC. We assumed PBT led to a 25% reduction in long-term xerostomia, short-term dysgeusia, and the need for gastrostomy tube. Fewer dental complications were also expected with PBT. Incremental cost-effectiveness ratios (ICERs) were calculated, and value of information analyses were performed. The societal willingness-to-pay was defined as $100K per quality-adjusted life year (QALY). RESULTS: The ICERs for PBT for favorable human papillomavirus (HPV)-positive OPC were $288,000/QALY and $390,000/QALY in the payer perspective (PP) and societal perspective, respectively. Under nearly every scenario, PBT was not cost-effective, with ICERs above $150,000/QALY in the PP. The ICERs for HPV-negative OPC were typically greater than $250K/QALY in both perspectives. For HPV-positive patients, the ICER was less than $100,000/QALY in the PP only in younger patients who experienced a 50% reduction in both xerostomia and gastrostomy use. On probabilistic sensitivity analyses, there were 0% and 0.4% probabilities that PBT was cost-effective for 65- and 55-year old patients, respectively. The value of information was zero or negligible for all ages and perspectives at willingness-to-pay of $100,000/QALY and only meaningful in the PP for younger patients at a willingness-to-pay of $150,000/QALY. CONCLUSIONS: Intensity modulated proton beam therapy was only cost-effective in the PP if assumed to achieve profound reductions in long-term morbidity for younger patients; it was never cost-effective in the societal perspective. Prospective data are needed (and may be valuable) to better characterize the comparative toxicities of these treatments but are unlikely to change this calculation, except potentially in the most favorable cohort of patients.