Human Papillomavirus (HPV) and Oropharyngeal Squamous Cell Carcinoma

Epidemiology and Association

Approximately 72% of newly diagnosed head and neck cancer patients are HPV-positive, with oral HPV infection associated with a 12.3-fold increased risk for head and neck cancer, according to the Journal of Microbiology, Immunology and Infection 1, 2
HPV type 16 infection specifically carries the highest risk, with an odds ratio of 14.6 for head and neck cancer and 22.4 for oropharyngeal squamous cell carcinoma, as reported by the Journal of Microbiology, Immunology and Infection 1, 2
The prevalence of oropharyngeal cancer attributable to HPV varies globally but is estimated at around 30-35%, as estimated by Annals of Oncology 3

HPV evaluation using p16 immunohistochemistry (IHC) should be performed on all patients with newly diagnosed oropharyngeal SCC, as recommended by Annals of Oncology 4, 5
p16 IHC is a reliable surrogate marker for HPV positivity in the oropharynx, although 10-15% of false-positive results can occur, according to Annals of Oncology 5
For neck metastases of unknown origin, p16 status should be assessed, and if positive, another specific HPV test (e.g., DNA, RNA, or in situ hybridization) should be performed to confirm HPV status, as suggested by Annals of Oncology 5

Patients with HPV-positive OPSCC have distinct characteristics, including being younger, nonsmokers, and nondrinkers compared to those with HPV-negative disease, as noted by Annals of Oncology 3

HPV vaccination has been shown to be effective in preventing oropharyngeal infections caused by HPV types 16 and 18 (82.4% efficacy) and against non-vaccine HPV types 31 and 45 (75.3% efficacy), as reported by the Journal of Microbiology, Immunology and Infection 1, 2
The risk of developing oropharyngeal cancer in unvaccinated individuals is 19 times higher than in vaccinated groups, according to the Journal of Microbiology, Immunology and Infection 1, 2

Diagnostic workup for suspected oropharyngeal cancer should include complete physical examination with neck palpation, flexible head and neck fibreoptic endoscopy, pathological confirmation, and imaging studies, as recommended by Annals of Oncology 5
Key symptoms prompting evaluation include chronic pain in the throat, persistent hoarseness, painful or difficult swallowing, and neck masses, as noted by Annals of Oncology 3

Human papillomavirus (HPV) causes oropharyngeal cancer primarily through the expression of viral oncoproteins E6 and E7, which inactivate crucial tumor suppressor genes p53 and pRb, leading to loss of cell-cycle control, impaired cell differentiation, and p16 protein overexpression 6, 7
HPV DNA integrates into the host cell chromosome during carcinogenic progression, resulting in consistent expression of viral oncoproteins E6 and E7 in HPV-positive carcinomas 6
The viral oncogenes E6 and E7 inactivate crucial human tumor suppressor genes, specifically: E6 inactivates p53 tumor suppressor protein and E7 inactivates retinoblastoma protein (pRb) 7
This inactivation leads to loss of cell-cycle control and impaired cell differentiation 6
The disruption of normal cell regulation results in p16 protein overexpression, which serves as a reliable surrogate marker for HPV-driven tumorigenesis in oropharyngeal cancers 6

HPV type 16 (HPV16) is the predominant subtype responsible for the vast majority of HPV-related oropharyngeal cancers 7
HPV types 18, 31, and 33 account for most of the remaining HPV-positive oropharyngeal cancers 7
Oral HPV16 infection increases the risk of oropharyngeal cancer, with a strong causal relationship established 7

Approximately 60-70% of newly diagnosed oropharyngeal cancers in the United States and parts of the European Union are attributable to HPV 7
Patients with HPV-related oropharyngeal cancers tend to be younger 8

p16 immunohistochemistry (IHC) serves as a reliable surrogate marker for HPV positivity specifically in oropharyngeal tumors 6
For definitive HPV testing, additional methods include PCR and in situ hybridization (ISH) 7