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Molecular prognostic indicators in HPV-positive oropharyngeal cancer: an updated review

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Abstract

Infection with HPV virus and exposure to extrinsic carcinogens are the main causative factors for oropharyngeal squamous cell carcinoma (OPSCC). While HPV-related OPSCC typically shows a better prognosis and may be a candidate for de-intensification therapy, there is a subset of HPV-related cancers that show aggressive phenotype with frequent metastatic spread. The identification and refinement of molecular markers can better serve for prediction of prognosis and thus improve treatment decisions and outcome. We conducted a systematic review according to the PRISMA guidelines of all relevant studies addressing novel biomarkers in publications prior to July 2021. We identified studies that evaluated the association between molecular markers and prognosis in HPV-positive OPSCC. Full-text publications were entirely reviewed, classified, and selected if a clear predictive/prognostic value was seen in patients with HPV-positive OPSCC. Furthermore, a functional analysis of the target genes was conducted to understand biological processes and molecular pathways impacting on HPV-positive OPSCC outcomes. The systematic review yielded a total of 14 studies that matched the inclusion and exclusion criteria. Differential expression was identified for 31 different biomarkers. The first common pattern identified was the association of HPV-related circulating antibodies to activated immune function. Second, gene–gene interaction analysis further identified interacting gene networks tightly implicated in hypoxia tumor metabolism including the Warburg effect. Survival in HPV-positive OPSCC can be predicted by distinct selective biomarkers mainly indicative of immune host response and oxidative metabolism. Among these markers, some were identified to be unsuitable for HPV-positive de-escalation trials aimed at improving patients’ quality of life.

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Fig. 1

reproduced from Moher, Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement; published by PLoS Med., 2009 [18]

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Acknowledgements

This study was supported by FRQ-S/RSBO#35376 (258000 and 258259) and CIHR-NCOHR (New Frontier Seed Grant 2020-2022).

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Authors and Affiliations

  1. Department of Otolaryngology Head and Neck Surgery, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, 3755 Côte Ste-Catherine Road, Montreal, QC, H3T 1E2, Canada

    Gregoire B. Morand, Alina Diaconescu, Iman Ibrahim, Genevieve Lamarche, Jacqueline Dalfen, Michael P. Hier & Sabrina Daniela da Silva

  2. Departments of Medicine, Oncology, and Pharmacology and Therapeutics, Faculty of Medicine, Segal Cancer Centre and Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, 3755 Côte Ste-Catherine Road, Montreal, QC, H3T 1E2, Canada

    Gregoire B. Morand, Moulay A. Alaoui-Jamali & Sabrina Daniela da Silva

  3. Department of Structural and Functional Biology, Institute of Biology, Universidade Estadual de Campinas (UNICAMP) and Boldrini Children’s Center, Campinas, Sao Paulo, Brazil

    Juliana S. Ruas & Mariana Maschietto

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  1. Gregoire B. Morand
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Correspondence to Sabrina Daniela da Silva.

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Morand, G.B., Diaconescu, A., Ibrahim, I. et al. Molecular prognostic indicators in HPV-positive oropharyngeal cancer: an updated review. Clin Exp Metastasis 39, 407–416 (2022). https://doi.org/10.1007/s10585-022-10148-9

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