AtlasOral CancerHPV-associated Oropharyngeal SCC

Oral Cancer

HPV-associated Oropharyngeal SCC

aka HPV-OPSCC

A biologically and epidemiologically distinct SCC of the tonsil and base of tongue driven by high-risk HPV-16; better prognosis than tobacco-related SCC and staged separately in AJCC 8.

Virus
HPV-16
Marker
p16 block+
5-y OS
≈75–85%

§ 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)

Question 1

Most common HPV type in OPSCC:

Question 2

IHC surrogate marker for HPV:

Question 3

Prognosis of HPV+ compared with HPV− OPSCC:

References

  1. Chaturvedi AK. J Clin Oncol 2011
  2. AJCC 8th Edition

Draft — pending faculty review. Educational use only; verify against current guidelines and primary sources before clinical application.