Diversity of cancer stem cells in head and neck carcinomas: The role of HPV in cancer stem cell heterogeneity, plasticity and treatment response

• Published in: Radiotherapy and oncology 2019-06, Vol.135, p.1-12
• Main Authors: Reid, Paul, Marcu, Loredana G., Olver, Ian, Moghaddasi, Leyla, Staudacher, Alexander H., Bezak, Eva
• Format: Article
• Language: English
• Subjects: Animals; Cancer Stem Cell; Cell Plasticity - physiology; Head and neck cancer; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - therapy; Head and Neck Neoplasms - virology; HNSCC; HPV; Humans; Neoplasm Recurrence, Local - pathology; Neoplasm Recurrence, Local - virology; Neoplastic Stem Cells - pathology; Neoplastic Stem Cells - virology; OPSCC; Papillomaviridae - physiology; Papillomavirus Infections - metabolism; Papillomavirus Infections - pathology; Prognosis; Radio-chemotherapy; Squamous Cell Carcinoma of Head and Neck - pathology; Squamous Cell Carcinoma of Head and Neck - therapy; Squamous Cell Carcinoma of Head and Neck - virology
• ISSN: 0167-8140; 1879-0887
• DOI: 10.1016/j.radonc.2019.02.016

•Prevalence of HPV positive cancers among OPSCC is increasing.•Cancer stem cells set therapy benchmark for tumour control.•HPV positive HNSCC cancer stem cells are more radiosensitive than HPV negative.•Multiple biomarker profiling can more specifically stratify patients for treatment. Head and neck squamous cell carcinomas (HNSCC) resulting from oncogenic transformations following human papillomavirus (HPV) infection consistently demonstrate better treatment outcomes than HNSCC from other aetiologies. Squamous cell carcinoma of the oropharynx (OPSCC) shows the highest prevalence of HPV involvement at around 70–80%. While strongly prognostic, HPV status alone is not sufficient to predict therapy response or any potential dose de-escalation. Cancer stem cell (CSC) populations within these tumour types represent the most therapy-resistant cells and are the source of recurrence and metastases, setting a benchmark for tumour control. This review examines clinical and preclinical evidence of differences in response to treatment by the HPV statuses of HNSCC and the role played by CSCs in treatment resistance and their repopulation from non-CSCs. Evidence was collated from literature searches of PubMed, Scopus and Ovid for differential treatment response by HPV status and contribution by critical biomarkers including CSC fractions and chemo-radiosensitivity. While HPV and CSC are yet to fulfil promise as biomarkers of treatment response, understanding how HPV positive and negative aetiologies affect CSC response to treatment and tumour plasticity will facilitate their use for greater treatment individualisation.