International Journal of Clinical Oncology

, Volume 21, Issue 5, pp 819–826 | Cite as

The molecular mechanism of human papillomavirus-induced carcinogenesis in head and neck squamous cell carcinoma

  • Daisuke SanoEmail author
  • Nobuhiko Oridate
Invited Review Article


Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Recently, the incidence of oropharyngeal cancer (OPC) has increased markedly in comparison to that of HNSCC, which is associated with the use of tobacco or alcohol or both. This increase has resulted mainly from the global rise in the number of human papillomavirus (HPV)-related oropharyngeal cancers (HPV-OPCs). HPV-OPC has several unique characteristics, including presentation in younger patients, better response rates to treatment, and better prognosis compared to alcohol- and smoking-related HNSCC. HPV infection status is now an independent prognostic factor for survival in patients with OPC. In general, HPV oncoproteins E6 and E7 are the primary viral factors responsible for the initiation and progression of HPV-related cancers via the inactivation of p53 and pRb. However, alterations in additional factors, including genomic instability, HPV DNA integration, and epigenetic alterations, could be equally important for neoplastic transformation and tumor progression. The impact of genomic instability and external environmental factors on the initiation of cervical cancer development through high-risk HPV infection has been well characterized, although less is known about the mechanism underlying HPV-induced carcinogenesis in HNSCC. This review provides an overview of the biology and molecular mechanisms of HPV-related cancers, including a particular focus on several recent studies on the comprehensive characterization of genomic alterations in HPV-associated HNSCC.


Head and neck squamous cell carcinoma Human papillomavirus (HPV)-related oropharyngeal cancers HPV oncoproteins Genomic instability HPV DNA integration 



The authors received no specific support or funding for this work.

Compliance with ethical standards

Conflict of interest

We, the authors, declare that we have no competing interests.


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Copyright information

© Japan Society of Clinical Oncology 2016

Authors and Affiliations

  1. 1.Department of Otorhinolaryngology, Head and Neck SurgeryYokohama City University, School of MedicineYokohamaJapan

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