HPV-associated Oropharyngeal SCC

§ overviewOverview

Squamous cell carcinoma of the oropharynx associated with transcriptionally active high-risk human papillomavirus (predominantly HPV-16).

§ icdICD Classification

C10

§ etiologyEtiology

• 01HPV-16 (>90% of HPV-OPSCC), HPV-18/33 less commonly
• 02Oral–oral and oral–genital sexual transmission

§ riskRisk Factors

• 01Number of lifetime sexual partners
• 02Oral sex
• 03Immunosuppression
• 04Male (M:F 4:1)

§ epidemiologyEpidemiology

Rising incidence in Western countries; now exceeds cervical cancer incidence in some populations; younger, non-smoking patients.

§ pathogenesisPathogenesis

HPV E6 inactivates p53; E7 inactivates pRB → cell cycle dysregulation; p16INK4a strongly upregulated as surrogate marker.

§ clinicalClinical Features

• 01Painless neck lump (cystic level II lymphadenopathy) often presenting feature
• 02Sore throat, dysphagia, referred otalgia
• 03Tonsillar asymmetry or base-of-tongue mass

§ differentialDifferential Diagnosis

• 01Tobacco-related HNSCC (p16 negative)
• 02Lymphoma
• 03Branchial cyst (in older adult with SCC — suspect metastasis)

§ investigationsInvestigations

• 01p16 IHC (surrogate; block staining >70% cells positive)
• 02HPV DNA PCR / RNA in situ hybridisation (confirmatory)
• 03MRI head-neck
• 04PET-CT for staging and unknown primary
• 05EUA with biopsy of tonsil / tongue base

§ ihcIHC / Special Stains

• 01p16 strongly positive (block-like)
• 02Confirm HPV with ISH/PCR to avoid false-positives

§ tnmTNM Staging

AJCC 8: separate staging for HPV-positive OPSCC — clinical N based on number and size of nodes; overall stage grouping generally lower than p16-negative disease.

§ treatmentTreatment

• 01Concurrent chemoradiation (cisplatin) — standard for locally advanced disease
• 02Transoral robotic surgery (TORS) with neck dissection for selected T1-T2 lesions ± adjuvant therapy
• 03De-escalation trials ongoing (reduced-dose RT)

§ complicationsComplications

• 01Mucositis, xerostomia, dysphagia, ORN, hypothyroidism

§ prognosisPrognosis

5-year overall survival ≈ 75–85% (vs 40–50% for p16-negative OPSCC).

§ preventionPrevention

• 01Prophylactic HPV vaccination (Gardasil-9)
• 02Safer sexual practices

§ examKey Examination Points

• 01Cystic neck node in adult non-smoker → work up for HPV-OPSCC
• 02Test p16 on every OPSCC

§ revisionQuick Revision Summary

• 01HPV-16 · p16+ · better prognosis · AJCC 8 separate staging · TORS or chemoRT

§ vivaBDS Viva Questions

• 01Why is p16 a surrogate for HPV?
• 02Staging difference in AJCC 8?
• 03Role of HPV vaccination in prevention?

§ mcqsMCQs — Assessment (3)

§ relatedRelated Diseases