Projected Association of Human Papillomavirus Vaccination With Oropharynx Cancer Incidence in the US, 2020-2045

Zhang, Yuehan; Fakhry, Carole; D’Souza, Gypsyamber

doi:10.1001/jamaoncol.2021.2907

Cited by 72 publications

(71 citation statements)

References 47 publications

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“…Vaccination will decrease the incidence of HPV-associated OPSCC only after 2045, because of the lack of vaccination in older age cohorts. 39 Another notable finding of this study was the increase in p16-positive and ISH-positive non-OPSCCs. Neither has previously been detected, likely due to their low prevalence and the lack of prospective studies in the last 10 years.…”

Section: Discussionmentioning

confidence: 53%

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Prevalence of human papillomavirus in head and neck cancers at tertiary care centers in the United States over time

Scott‐Wittenborn

D’Souza

Tewari

et al. 2022

Cancer

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BACKGROUND: Human papillomavirus (HPV) is responsible for a growing proportion of oropharyngeal squamous cell carcinomas (OPSCCs) among men and White individuals. Whether similar trends apply to women, non-Whites, and non-oropharyngeal squamous cell carcinomas (non-OPSCCs) is unknown. METHODS: This is a cross-sectional analysis combining 2 multi-institutional case series of incident head and neck squamous cell carcinoma (HNSCC) cases. Incident HNSCCs from 1995 to 2012 were enrolled retrospectively using banked tumor samples and medical record abstraction. Incident HNSCCs from 2013 to 2019 were enrolled prospectively. The prevalence of tumor HPV biomarkers was tested over 3 time periods (1995-2003, 2004-2012, and 2013-2019). Centralized testing was done for p16 immunohistochemistry (p16) and oncogenic HPV in situ hybridization (ISH). RESULTS: A total of 1209 incident cases of HNSCC were included. Prevalence of p16-and ISH-positive tumors increased significantly for oropharynx cancers over time. The majority were positive after 2013 for White patients (p16, 92%; P < .001; ISH 94%; P < .001), Black patients (p16, 72%; P = .021; ISH 67%; P = .011), and Hispanic patients (p16, 100%; P = .04; ISH 100%; P = .013). For women with OPSCC, the prevalence of p16-and ISH-positive tumors increased significantly to 82% (P < .001) and 78% (P = .004), respectively. For non-OPSCCs, there was increased p16 and ISH positivity overall with 24% p16 and 16% ISH positivity in the most recent time period (P < .001 for both). CONCLUSIONS: The majority of OPSCCs in US tertiary care centers are now p16 and ISH positive for all sex and race groups. In some populations in the United States, 91% of OPSCCs are now caused by HPV. Few non-OPSCCs are p16 and ISH positive.

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Section: Discussionmentioning

confidence: 53%

“…Similarly, increased oral sex and prevalence of p16‐ and ISH‐positive OPSCC tumors among non‐White groups portends an increase in incidence of HPV‐associated OPSCCs. Vaccination will decrease the incidence of HPV‐associated OPSCC only after 2045, because of the lack of vaccination in older age cohorts 39 …”

Section: Discussionmentioning

confidence: 99%

Prevalence of human papillomavirus in head and neck cancers at tertiary care centers in the United States over time

Scott‐Wittenborn

D’Souza

Tewari

et al. 2022

Cancer

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“…Despite the introduction of HPV vaccination programmes for boys in several countries in the past few years and demonstrable efficacy against oral HPV infection, HPV + OPSCC rates are likely to rise further over the next 20–30 years, before the full benefits of comprehensive gender-neutral vaccination are manifest. Indeed, on the basis of current vaccination rates in the USA, the incidence of HPV + OPSCC will continue to climb substantially among those who were not vaccinated as children between now and 2045, with meaningful reductions confined to those <56 years of age, who already have a lower risk of diagnosis and among whom the protective effects of vaccination will begin to be manifest during this period 56 , 57 . Consequently, substantial morbidities, mortality and broader societal costs are to be expected.…”

Section: Epidemiologymentioning

confidence: 99%

HPV-associated oropharyngeal cancer: epidemiology, molecular biology and clinical management

et al. 2022

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Oropharyngeal squamous cell carcinoma (OPSCC) comprises cancers of the tonsils, base of tongue, soft palate and uvula (Fig. 1). Like other head and neck squamous cell carcinomas (HNSCCs), OPSCC has historically been linked to alcohol and tobacco consumption. A reduction in the prevalence of smoking in most high-income countries over the past 20 years has led to a decline in the incidence of HNSCC; however, carcinogenic human papillomavirus (HPV) infection has emerged as an important risk factor that has driven an increase in the incidence of OPSCC over the same period. More specifically, HPV now accounts for 71% and 51.8% of all OPSCCs in the USA and UK, respectively [1][2][3][4] . Of these, 85-96% are caused by HPV-16 infections and are therefore expected to be preventable by prophylactic HPV vaccination, which is known to be effective in preventing HPV-associated cervical neoplasia and is now being administered to both boys and girls in several countries 4,5 . The most recent edition of the American Joint Committee on Cancer (AJCC) staging system defined HPV-positive (HPV + ) and HPV-negative (HPV -) OPSCCs as separate entities, with distinct molecular profiles, tumour characteristics and outcomes 6 (Table 1). Importantly, the former is associated with a more favourable prognosis 7 . In this Review, we provide a comprehensive overview of HPV + OPSCC, focusing on how our increasing knowledge of disease biology has informed clinical practice and is guiding the pursuit of improved treatments. Epidemiology Rising incidence, particularly in menAmong all cancers, OPSCC has one of the most rapidly rising incidences in high-income countries 8,9 . An increasing incidence of this disease has been observed in the UK, USA, across Europe, New Zealand and in parts of Asia [9][10][11][12][13][14][15][16][17][18][19] . In both the UK and the USA, the incidence of oropharyngeal cancer in men has surpassed that of cervical cancer in women 8 (Fig. 1). Globally, the percentage of OPSCCs that are HPV + was reported in 2021 to be 33%; however, prevalence varies considerably depending on the geographical region, with estimates ranging from 0% in southern India to 85% in Lebanon 20 .HPV + OPSCC is more prevalent than HPV -OPSCC among those who do not consume tobacco or alcohol; however, a substantial history of tobacco and alcohol use remains prominent in patients with the former and is associated with worse outcomes 21,22 . Furthermore, sexual behaviour is an established risk factor for HPV + OPSCC, with a strong association observed between number of

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“…The role of upfront TORS in elderly patients with OPSCC remains controversial. It is apparent that over time the demographic profile of the typical patient with HPV related OPSCC is changing ( 24 , 25 ). Recent modelling predicts that the incidence of HPV+ OPSCC in the USA will rise in patients 65 years of age and older from 40.7 to 71.2 per 100,000 by 2029 ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

Perioperative Mortality Risk in Patients Undergoing Transoral Robotic Surgery for T1-T2 Oropharyngeal Squamous Cell Carcinoma: A National Cancer Database Study

et al. 2022

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The National Cancer Database is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. The American College of Surgeons and the Commission on Cancer have not verified and are not responsible for the analytic or statistical methods used or for the conclusions drawn from these data by the investigators.IntroductionTransoral robotic surgery (TORS) is well established as initial definitive treatment for early-stage oropharyngeal squamous cell carcinoma (OPSCC) as an alternative to radiation therapy with similar survival rates. While proponents of TORS focus on the reduced morbidity of treatment compared to open procedures, shortened hospital admissions and equivalent survival outcomes to non-surgical treatment, there remain concerns over the risk of mortality within the acute perioperative period. Therefore, we sought to determine the 30-day and 90-day perioperative mortality risk using the National Cancer Database.MethodsA retrospective cohort analysis was performed for patients diagnosed with pathologic T1/2 OPSCC between January 1, 2010, and December 31, 2016 that underwent primary surgical treatment with TORS and was not restricted by HPV status. The primary outcome was 30-day perioperative mortality. The secondary outcome was 90-day perioperative mortality. Univariable analysis was used to identify variables associated with 30-day perioperative mortality.ResultsIn total, 4,127 patients (mean [SD; range] age, 59 [9.5; 22-90] years; 3,476 [84%] men and 651 [16%] women) met inclusion criteria. The number of patients with pT1-2 OPSCC undergoing TORS increased three-fold between 2010 (279/4,127; 7%) to 2016 (852/4,127; 21%). The overall 30-day and 90-day perioperative mortality rate for TORS during the study period was 0.6% (23/4,127) and 0.9% (38/4,127), respectively. On univariable analysis (UVA), age≥65 was the only predictor of 30-day perioperative mortality (OR 3.41; 95% CI 1.49-7.81).ConclusionThe overall risk of all cause mortality following TORS for early-stage OPSCC remains low. The risk of mortality is higher in elderly patients and should be considered, in addition to previously established risk factors, during patient selection and counselling.

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Projected Association of Human Papillomavirus Vaccination With Oropharynx Cancer Incidence in the US, 2020-2045

Cited by 72 publications

References 47 publications

Prevalence of human papillomavirus in head and neck cancers at tertiary care centers in the United States over time

Prevalence of human papillomavirus in head and neck cancers at tertiary care centers in the United States over time

HPV-associated oropharyngeal cancer: epidemiology, molecular biology and clinical management

Perioperative Mortality Risk in Patients Undergoing Transoral Robotic Surgery for T1-T2 Oropharyngeal Squamous Cell Carcinoma: A National Cancer Database Study

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