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Review

Molecular Tumor Subtypes of HPV-Positive Head and Neck Cancers: Biological Characteristics and Implications for Clinical Outcomes

by 1,2,†, 1,†, 1,3, 1 and 1,2,*
1
Department of Computational Medicine and Bioinformatics, Medical School, University of Michigan, Ann Arbor, MI 48109, USA
2
Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA
3
Department of Computer Science, LS&A, University of Michigan, Ann Arbor, MI 48109, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Frank Traub
Cancers 2021, 13(11), 2721; https://doi.org/10.3390/cancers13112721
Received: 30 April 2021 / Revised: 24 May 2021 / Accepted: 27 May 2021 / Published: 31 May 2021
(This article belongs to the Special Issue Human Papillomavirus and Head and Neck Cancer)
Human papillomavirus (HPV) infections are responsible for a continually growing number of head and neck cancer (HNC) cases, with the incident rate overtaking that of HPV-related cervical cancers in the United States. Most HPV-related HNC cases arise in the oropharynx, and although they have a better 5-year survival rate than non-HPV-related HNC patients (80% compared to 50%), de-escalating treatment in all HPV(+) patients in an attempt to improve quality of life led to unacceptable results. Studying molecular subtypes of HPV(+) HNC can help to identify treatment regimens tailored to each patient’s tumor characteristics. We synthesized information from several studies of HPV(+) HNC subtypes, and describe three main groups that differ by their immune cell content, level of keratinocyte differentiation, degree of epithelial-to-mesenchymal transition, probability of HPV integration, oxidoreductase activity and stromal cell (e.g., cancer-associated fibroblast) content. The differences have important implications for local or distant recurrence, treatment response and survival.
Until recently, research on the molecular signatures of Human papillomavirus (HPV)-associated head and neck cancers mainly focused on their differences with respect to HPV-negative head and neck squamous cell carcinomas (HNSCCs). However, given the continuing high incidence level of HPV-related HNSCC, the time is ripe to characterize the heterogeneity that exists within these cancers. Here, we review research thus far on HPV-positive HNSCC molecular subtypes, and their relationship with clinical characteristics and HPV integration into the host genome. Different omics data including host transcriptomics and epigenomics, as well as HPV characteristics, can provide complementary viewpoints. Keratinization, mesenchymal differentiation, immune signatures, stromal cells and oxidoreductive processes all play important roles. View Full-Text
Keywords: human papillomavirus; head and neck cancer; cancer subtypes; gene expression; oropharynx; HPV integration; immune response; keratinization human papillomavirus; head and neck cancer; cancer subtypes; gene expression; oropharynx; HPV integration; immune response; keratinization
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MDPI and ACS Style

Qin, T.; Li, S.; Henry, L.E.; Liu, S.; Sartor, M.A. Molecular Tumor Subtypes of HPV-Positive Head and Neck Cancers: Biological Characteristics and Implications for Clinical Outcomes. Cancers 2021, 13, 2721. https://doi.org/10.3390/cancers13112721

AMA Style

Qin T, Li S, Henry LE, Liu S, Sartor MA. Molecular Tumor Subtypes of HPV-Positive Head and Neck Cancers: Biological Characteristics and Implications for Clinical Outcomes. Cancers. 2021; 13(11):2721. https://doi.org/10.3390/cancers13112721

Chicago/Turabian Style

Qin, Tingting, Shiting Li, Leanne E. Henry, Siyu Liu, and Maureen A. Sartor 2021. "Molecular Tumor Subtypes of HPV-Positive Head and Neck Cancers: Biological Characteristics and Implications for Clinical Outcomes" Cancers 13, no. 11: 2721. https://doi.org/10.3390/cancers13112721

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