Role of HPV in Oropharyngeal Cancer

Epidemiology and Causal Relationship

The American Cancer Society and National Comprehensive Cancer Network recommend that HPV is now established as the principal causative agent in 60-70% of newly diagnosed oropharyngeal squamous cell carcinomas (OPSCC) in the United States and European Union, with HPV type 16 being responsible for the vast majority of cases 1, 2
The incidence of HPV-positive OPSCC has increased dramatically by 29.0%-93.0% between 2002 and 2011, with males showing a 47.1% increase and females 37.5% 3
HPV-associated OPSCC is projected to surpass cervical cancer incidence by 2020 4
Oral HPV infection confers a 12.3-fold increased risk for head and neck cancer, with HPV-16 specifically carrying an odds ratio of 22.4 for OPSCC 3

The National Comprehensive Cancer Network states that HPV causes oropharyngeal cancer through viral oncoproteins E6 and E7, which inactivate tumor suppressor genes p53 and pRb respectively, leading to loss of cell-cycle control and p16 protein overexpression 2
HPV DNA integrates into the host cell chromosome during carcinogenic progression 2
E6 inactivates p53 tumor suppressor protein while E7 inactivates retinoblastoma protein (pRb) 2

The American College of Pathologists recommends that HPV tumor status must be determined for all newly diagnosed oropharyngeal squamous cell carcinomas using p16 immunohistochemistry as the primary testing method 4, 5, 2
p16 IHC should be performed on either the primary tumor or cervical nodal metastases (only if an oropharyngeal primary is present) 4, 5
The threshold for p16 positivity is at least 70% nuclear and cytoplasmic expression with moderate to strong intensity 4

The National Comprehensive Cancer Network recommends that HPV status should be used as a stratification factor in clinical trials, but currently should NOT routinely alter treatment selection outside of clinical trials 1, 5
Patients with HPV-positive cancers demonstrate improved response to treatment, improved overall survival, and improved progression-free survival compared to HPV-negative tumors 1, 5

The National Comprehensive Cancer Network recommends that early-stage HPV-positive oropharyngeal cancers may be treated with either primary surgery (including transoral robotic surgery with neck dissection) or definitive radiotherapy 1, 5
Concurrent chemoradiotherapy with cisplatin 100 mg/m² every 3 weeks is the preferred category 1 treatment approach for locally advanced resectable HPV-positive oropharyngeal cancer 5
Postoperative concurrent chemoradiotherapy is category 1 recommended for extracapsular nodal spread and/or positive mucosal margins 1, 5

The Centers for Disease Control and Prevention state that HPV vaccination has demonstrated 82.4% efficacy in preventing oropharyngeal infections caused by HPV types 16 and 18, and 75.3% efficacy against non-vaccine types 31 and 45 2
The risk of developing oropharyngeal cancer in unvaccinated individuals is 19 times higher than in vaccinated groups 2

The American Academy of Otolaryngology-Head and Neck Surgery recommends that clinicians must be prepared to counsel patients regarding sexually transmitted disease transmission, sexual health inquiries, and emotional wellbeing related to HPV-positive diagnosis 3, 6, 7, 8