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

Abstract

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

Human Papillomavirus Detected in Oropharyngeal Cancers from Chilean Subjects

“…Interestingly, De Cicco et al [29] collected specimens from a private institution and reported an HPV frequency similar to this study. Another factor potentially involved may be related to the time of samples storage in the reports with low HPV prevalence, not only due to the possible degradation of the genetic material, but also because the samples were taken prior to the epidemiological increase in HPV (+) OPSCCs that occurred over the last two decades [35]. Another difficulty in comparing reports is the use of different methods for HPV detection which show different sensitivities and specificities [30,31].…”

It Takes Two to Tango: A Review of Oncogenic Virus and Host Microbiome Associated Inflammation in Head and Neck Cancer

“…This is thought to be due to baseline chromosomal instability in patients exposed to tobacco products than those who are not [98]. Though the field is beginning to consider the role of the oral microbiome in the pathogenesis of oral cavity cancer, to our knowledge the microbiome has not yet been examined as a factor related to HPV positive OPSCC [99].…”

High Risk-Human Papillomavirus in HNSCC: Present and Future Challenges for Epigenetic Therapies

“…HPV+ HNSCC represent approximately 25% of the worldwide HNSCC cases, and their incidence is different depending on the tumor anatomical site. The highest levels are observed among Oropharyngeal Squamous Cell Carcinomas (OPSCC): nearly 70% of HPV+ HNSCC cases occur in the oropharynx and approximately 60% to 70% of OPSCC are HPV+ [ 1 , 6 , 7 ]. One of the main reasons for this distribution is probably due to the discontinuous single-layered epithelium organization that characterizes the oropharyngeal region and that is more prone to carcinogenic transformation compared to the epithelia of other anatomical sites [ 1 , 4 ].…”

“…Even though generally higher in males, this ratio can be different according to the geographical area. Importantly, this sex unbalance in HNSCC seems to be independent from the HPV status: indeed, the male to female ratio in HPV+ HNSCC spans from 3 to 6 [ 6 ] and, considering only OPSCC, of which approximately 60–70% are hr-HPV-positive tumors [ 7 ], the prevalence remains higher in men than in women. Moreover, women with HPV+ HNSCC seem to have improved overall survival compared to men [ 130 ].…”