Human Papillomavirus-Associated Oropharyngeal Cancer: Global Epidemiology and Public Policy Implications

Abstract

Global trends in human papillomavirus (HPV)-associated head and neck cancers (HNC), specifically in the oropharynx subsite, have been dynamically changing, leading to new staging and treatment paradigms. Epidemiologic studies have noted regional variations in HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). While HPV vaccination remains the main preventative approach, vaccination policy in relation to gender neutrality is heterogeneous and particularly sparse in low- and middle-income countries, where the burden of global cancer cases and HPV-associated HNC are not well-characterized in certain regions. This review summarizes the existing literature on regional variations of HPV-associated OPSCC and gender-neutral vaccine policies. Based on available data, the incidence of HPV-associated OPSCC is highest in North America, Europe, and Oceania. As of 2022, 122 of 195 (63%) World Health Organization (WHO) member states had incorporated HPV vaccinations nationally; of these, 41 of 122 (34%) member states have introduced gender-neutral vaccine coverage. Future research is needed to describe continued evolving trends in HPV-associated OPSCC, understand underlying risk factors leading to regional variation in disease, and implement gender-neutral policy more broadly.

Changes in the Incidence and Human Papillomavirus-Positive Portion of Oropharyngeal Squamous Cell Carcinoma in Hong Kong

“…It has been estimated that about 30% of oropharyngeal cancers across the globe are driven by HPV [ 19 , 20 ]. In the United Sates, the population-level incidence of HPV-positive oropharyngeal cancers increased by 225% from 1988 to 2004 [ 21 ].…”

“…While a notable trend of increase in the incidence of HPV-associated oropharyngeal cancer has been reported across North America, Europe, and Australia, the findings from Asia are more varied. The age-standardized incidence of OPSCC in Asia is on the low side of 0.49 and 0.10 per 100,000 population in males and females, respectively [ 19 ]. However, a report from Taiwan showed that both HPV-related and -unrelated head and neck cancers increased during 1995–2009, with the fastest increase in tonsil cancer, particularly among men.…”

“…This is in line with the current understanding that tonsils are the most preferred site within the head and neck region for HPV-mediated carcinogenesis [ 31 , 32 ]. The incidence of OPSCC in Hong Kong and its trend of increase in HPV-positive proportion appear to be lower than Western countries [ 19 ]. This could be a result of a difference in exposure to oral HPV infection due to cultural differences in sexual, especially oral, sexual practices.…”

Human Papilloma Virus Positive Oropharyngeal Squamous Cell Carcinoma and the Immune System: Pathogenesis, Immunotherapy and Future Perspectives

“…The global incidence of OPSCC was over 3.7 million cases in 2020, 33% attributable to HPV [27,28], with the incidence of OPSCC rapidly increasing in developed countries when compared to all cancers [29,30]. This increase has been identified in the US, Europe, UK, Australia, New Zealand, and certain countries within Asia [28,[31][32][33][34][35][36][37], with further studies confirming a rising trend across all countries [34,[36][37][38][39][40][41][42]. HPV is the most common sexually transmitted infection (STI) and one of the most common viral infections in the world [43], and HPV + OPSCC has now achieved the notorious distinction of becoming the predominant HPV-related malignancy in the US and UK, superseding cervical cancer [44].…”

“…HPVs are highly epitheliotropic, infecting cutaneous and mucosal epithelial cells via an unconventional clathrin-independent endocytic pathway [75] and are strongly associated with cervical, head and neck, anogenital, and oesophageal cancers. Of the more than 200 HPV serotypes, 14 are characterised as HR-HPVs due to their carcinogenic potential, including HPV 16,18,31,33,35,39,45,51,52,56,58,59,66,and 68 [76]. For OPSCC specifically, HPV 16 has been identified in the majority of HPV + OPSCC cases, while HPV 18 and other HR-HPV serotypes have been identified in HPV + OPSCC cases, but are much less common [77].…”