Is there an association between Squamous Cell Carcinoma (SCC) of the tonsils and Human Papillomavirus (HPV) infection?

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Last updated: February 16, 2025View editorial policy

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From the Guidelines

Yes, there is a strong association between Squamous Cell Carcinoma (SCC) of the tonsils and Human Papillomavirus (HPV) infection.

Key Points

  • HPV infection is a well-established cause of squamous cancers of the oropharynx, particularly cancers of the tonsils and tongue base 1.
  • The HPV-attributable fraction in newly diagnosed oropharyngeal cancer is estimated at 60% to 70% in the United States and parts of the European Union 1.
  • Oral HPV type 16 (HPV16) infection increases the risk of oropharyngeal cancer, and a strong causal relationship has been established 1.
  • Over 70% of new cases of oropharyngeal HNSCC are attributable to HPV subtype 16 1.
  • Patients with HPV-associated H&N cancer tend to be younger, with a better performance status and prognosis 1.

HPV and SCC of the Tonsils

The evidence suggests that HPV infection, particularly HPV type 16, is a major risk factor for SCC of the tonsils. The increasing incidence of HPV-positive oropharyngeal cancer, including tonsil cancer, is attributed to the rising prevalence of high-risk HPV infection 1.

Clinical Implications

The association between HPV and SCC of the tonsils has important clinical implications, including the potential for prophylactic HPV vaccination to prevent HPV-attributed oropharyngeal cancer 1. Additionally, the diagnosis and treatment of HPV-positive OPSCC may differ from those of HPV-negative tumors, with HPV-positive patients tend to have a better prognosis 1.

From the Research

Association between Squamous Cell Carcinoma (SCC) of the tonsils and Human Papillomavirus (HPV) infection

  • There is evidence to suggest an association between SCC of the tonsils and HPV infection, with studies indicating that HPV-positive tonsillar SCC represents a specific entity with distinct etiology, molecular features, and outcome 2, 3.
  • HPV DNA was found in 62% of tonsillar SCC cases in one study, with the HPV16 genotype being the most common 2.
  • Another study found that HPV was identified in 46% of patients with TSCC, with HPV type 16 being present in 40% of cases 3.
  • The presence of HPV in tonsillar SCC has been associated with improved overall survival and disease-free survival, particularly in patients with oropharyngeal tumors 4.

HPV infection and tonsillar SCC

  • HPV infection has been identified as an independent risk factor for TSCC, with the odds of developing TSCC being 18.2 times greater in patients with HPV infection than in those without 3.
  • Patients with HPV-positive TSCC tend to be younger and have a better prognosis than those with HPV-negative TSCC 3, 5.
  • HPV-positive TSCC is often characterized by non-keratinizing, poorly differentiated or basaloid carcinomas, and is diagnosed in earlier T-category with a trend for a more advanced N-category 5.

Molecular characteristics of HPV-positive tonsillar SCC

  • HPV-positive tonsillar SCC is associated with distinct molecular features, including decreased pRB and increased p16 expression levels 2.
  • The expression of cytokeratin 7 (CK7) has been identified as a potential biomarker for HPV-related oropharyngeal SCC, with CK7-expressing tonsillar crypt cells potentially representing an oropharyngeal subsite susceptible to HPV-related SCC 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Squamous cell carcinoma of the tonsils: a molecular analysis of HPV associations.

Clinical cancer research : an official journal of the American Association for Cancer Research, 2002

Research

New insights into human papillomavirus-associated head and neck squamous cell carcinoma.

Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale, 2013

Research

Cytokeratin 7 in Oropharyngeal Squamous Cell Carcinoma: A Junctional Biomarker for Human Papillomavirus-Related Tumors.

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2017

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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