How does a Human Papillomavirus (HPV) infection connect to a sinus nasal cancerous growth?

HPV and Sinonasal Cancerous Growths: The Connection

HPV infection can directly contribute to sinonasal cancerous growths through its oncogenic properties, with up to 21-33% of sinonasal carcinomas testing positive for high-risk HPV strains, particularly HPV-16. 1, 2

Pathophysiological Connection Between HPV and Sinonasal Cancer

HPV Types and Prevalence

• High-risk HPV types (particularly type 16,18,31, and 33) are the predominant strains detected in sinonasal cancers 1
• Approximately 21% of sinonasal carcinomas are positive for high-risk HPV DNA 1
• HPV-related sinonasal carcinomas represent a distinct entity with specific characteristics

Mechanism of Carcinogenesis

• HPV infects the epithelial cells of the sinonasal tract
• Viral oncoproteins (E6 and E7) disrupt normal cell cycle regulation
• p16 overexpression is a reliable surrogate marker for HPV infection in these tumors, with 97% of HPV-positive sinonasal tumors exhibiting high p16 expression 1

Clinical and Histopathological Features

Histological Spectrum

• Most common type: Nonkeratinizing or partially keratinizing squamous cell carcinoma 1
• Other variants include:
  • Papillary squamous cell carcinoma
  • Adenosquamous carcinoma
  • Basaloid squamous cell carcinoma
  • HPV-related multiphenotypic sinonasal carcinoma (HMSC) 3, 4

Diagnostic Approach

• Definitive diagnosis requires endoscopic-guided biopsy of the sinonasal tumor 5
• HPV testing should be performed on all sinonasal carcinomas using:
  • p16 immunohistochemistry as an initial screening test
  • DNA in situ hybridization or PCR for confirmation of HPV presence 5
• Material should be collected in formalin or suitable fixative to allow for HPV testing 5

Clinical Significance and Prognosis

Prognostic Implications

• HPV-positive sinonasal carcinomas show a trend toward improved survival compared to HPV-negative tumors (hazard ratio=0.58) 1
• HPV-related multiphenotypic sinonasal carcinoma (HMSC) demonstrates an indolent clinical course despite aggressive radiological features 3, 4
• Some HPV-related sinonasal tumors may recur very late (even after decades) 4

Treatment Considerations

• Endoscopic surgical resection is often achievable despite complex radiological appearance 3
• Adjuvant radiation therapy is typically recommended following surgical resection 3
• HPV status should be determined as it may influence treatment decisions and prognostic discussions 6

Differential Diagnosis

Other Viral Associations

• While HPV is associated with sinonasal cancers, Epstein-Barr virus (EBV) is more commonly associated with nasopharyngeal carcinoma 5
• For neck metastases of unknown origin, both HPV and EBV status should be determined 5
• EBV testing is performed through Epstein-Barr-encoded RNA (EBER) using in situ hybridization 5

Pitfalls and Caveats

• Initial misdiagnosis is common due to morphologic overlap with other sinonasal tumors (particularly adenoid cystic carcinoma) 4
• HPV-related sinonasal tumors may have a heterogeneous etiology, with both HPV-related and non-related factors contributing 2
• Technical factors in testing may lead to discrepancies in HPV detection rates across studies 2
• The incidence of HPV-positive sinonasal cancers appears to be increasing, highlighting the importance of routine HPV testing 6