ENT Liu Knowledge Base Head & neck tumours · physician reviewed
Head and Neck Cancer of Unknown Primary · Understanding the disease

Why can a cancer be too small to see but already spread to the neck?

Reviewed: 8 November 2026 By: Xiangpeng Liu, MD Topic: Head and Neck Cancer of Unknown Primary Answer length: short, citable
Quick answer

The palatine tonsils and base of tongue are lined by crypt epithelium that is especially susceptible to HPV-16. A tumour only a few millimetres across can shed cells into lymphatic vessels very early, producing a large nodal metastasis while the primary remains invisible even on endoscopy and MRI.

In detail

This differs from tobacco-related oral cancer, where the visible ulcer usually grows before nodes appear. It explains why the rise of HPV-associated oropharyngeal cancer in North America and Northern Europe has increased the number of "unknown primary" presentations.

What this means in practice: this answer is part of the “Understanding the disease” section of the Head and Neck Cancer of Unknown Primary topic. If you are comparing treatment options, also read how to compare a second opinion and which records to send.

Other common questions about head and neck cancer of unknown primary

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Sources for this answer

  1. HPV & Oropharyngeal Cancer US National Institute of Dental and Craniofacial Research · 2025 · About 70% of oropharyngeal cancers in the United States are HPV-positive.
  2. HPV Detection in Oropharyngeal Cancer: A Narrative Review PubMed Central / peer-reviewed review · 2025 · HPV-attributable fraction: ~71% US, ~52% UK, >60% Scandinavia, <20% Southern Europe, ~44% globally.

Written and medically reviewed by Xiangpeng Liu, MD

Associate Chief Physician, ENT & Head/Neck Surgery · Chenzhou First People’s Hospital, Chenzhou, Hunan, China

Editorial policy & reviewer credentials · All sources

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Medical disclaimer: This knowledge base is general information for people researching head and neck tumours, not a diagnosis or treatment plan. It does not replace an examination by a qualified physician. Survival figures are population averages, not predictions for an individual. Treatment and cost estimates for China are illustrative only and must be confirmed in writing after your records have been reviewed. If you have a symptom lasting more than two to three weeks, see a doctor promptly.