Novel Immunotherapeutic Approaches to Treating HPV-Related Head and Neck Cancer

Nabil F Saba¹, Saagar Pamulapati², Bhamini Patel³, Mayur Mody⁴, Primož Strojan⁵, Robert Takes⁶, Antti A Mäkitie⁷, Oded Cohen⁸, Pia Pace-Asciak⁹, Jan B Vermorken^{10

11}, Carol Bradford¹², Arlene Forastiere¹³, Yong Teng¹, Andreas Wieland^{12

14

15}, Alfio Ferlito¹⁶

Affiliations

¹ Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
² Internal Medicine Program, Mercyhealth, Rockford, IL 61114, USA.
³ Department of Internal Medicine, Emory University, Atlanta, GA 30307, USA.
⁴ Hematology and Oncology Program, AdventHealth Medical Group, Calhoun, GA 30701, USA.
⁵ Department of Radiation Oncology, Institute of Oncology, 1000 Ljubljana, Slovenia.
⁶ Department of Otolaryngology and Head and Neck Surgery, Radboud University Medical Center, 6525 Nijmegen, The Netherlands.
⁷ Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital, University of Helsinki, Research Program in Systems Oncology, FI-00014 Helsinki, Finland.
⁸ Department of Otolaryngology, Ben Gurion University of the Negev, Soroka Medical Center, Be'er Sheva 84-101, Israel.
⁹ Department of Otolarynology-Head and Neck Surgery, University of Toronto, Toronto, ON M5S 1A1, Canada.
¹⁰ Department of Medical Oncology, Antwerp University Hospital, 2650 Edegem, Belgium.
¹¹ Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium.
¹² Department of Otolaryngology, The Ohio State University, Columbus, OH 43212, USA.
¹³ Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
¹⁴ Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210, USA.
¹⁵ Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
¹⁶ Coordinator of the International Head and Neck Scientific Group, 35100 Padua, Italy.

PMID: 37046621
PMCID: PMC10092986
DOI: 10.3390/cancers15071959

Review

Novel Immunotherapeutic Approaches to Treating HPV-Related Head and Neck Cancer

Nabil F Saba et al. Cancers (Basel). 2023.

. 2023 Mar 24;15(7):1959.

doi: 10.3390/cancers15071959.

Authors

Affiliations

¹ Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
² Internal Medicine Program, Mercyhealth, Rockford, IL 61114, USA.
³ Department of Internal Medicine, Emory University, Atlanta, GA 30307, USA.
⁴ Hematology and Oncology Program, AdventHealth Medical Group, Calhoun, GA 30701, USA.
⁵ Department of Radiation Oncology, Institute of Oncology, 1000 Ljubljana, Slovenia.
⁶ Department of Otolaryngology and Head and Neck Surgery, Radboud University Medical Center, 6525 Nijmegen, The Netherlands.
⁷ Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital, University of Helsinki, Research Program in Systems Oncology, FI-00014 Helsinki, Finland.
⁸ Department of Otolaryngology, Ben Gurion University of the Negev, Soroka Medical Center, Be'er Sheva 84-101, Israel.
⁹ Department of Otolarynology-Head and Neck Surgery, University of Toronto, Toronto, ON M5S 1A1, Canada.
¹⁰ Department of Medical Oncology, Antwerp University Hospital, 2650 Edegem, Belgium.
¹¹ Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium.
¹² Department of Otolaryngology, The Ohio State University, Columbus, OH 43212, USA.
¹³ Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
¹⁴ Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210, USA.
¹⁵ Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
¹⁶ Coordinator of the International Head and Neck Scientific Group, 35100 Padua, Italy.

PMID: 37046621
PMCID: PMC10092986
DOI: 10.3390/cancers15071959

Abstract

Head and neck cancer (HNC) is the seventh most common malignancy, with oropharyngeal squamous cell carcinoma (OPSCC) accounting for a majority of cases in the western world. While HNC accounts for only 5% of all cancers in the United States, the incidence of a subset of OPSCC caused by human papillomavirus (HPV) is increasing rapidly. The treatment for OPSCC is multifaceted, with a recently emerging focus on immunotherapeutic approaches. With the increased incidence of HPV-related OPSCC and the approval of immunotherapy in the management of recurrent and metastatic HNC, there has been rising interest in exploring the role of immunotherapy in the treatment of HPV-related OPSCC specifically. The immune microenvironment in HPV-related disease is distinct from that in HPV-negative OPSCC, which has prompted further research into various immunotherapeutics. This review focuses on HPV-related OPSCC, its immune characteristics, and current challenges and future opportunities for immunotherapeutic applications in this virus-driven cancer.

Keywords: HPV; human papillomavirus; immuno-oncology; immunotherapy; vaccine therapy.

PubMed Disclaimer

Conflict of interest statement

N.F.S. reports consulting role for Merck, GSK, CUE, AZ, BNT, Novartis, Eisai, Exelixis, and funding from BMS and Exelixis. A.W. is an inventor on a patent (US patent application No. 16/971,627) filed by Emory University related to HPV-specific monoclonal antibodies and HPV E2 as a potential immunological target in HPV-positive cancers and inventor on a patent application filed by Emory University related to the use of HPV-specific TCR sequences. Other authors report no conflict of interest, financial disclosures, or financial relationships regarding this submission.

Figures

**Figure 1**
HPV-related head and neck squamous cell carcinoma tumor microenvironment [53]. Key: Figure adopted with permission from SD da Silva, corresponding author of the manuscript “Implications and Emerging Therapeutic Avenues of Inflammatory Response in HPV+ Head and Neck Squamous Cell Carcinoma”. HPV: Human Papillomavirus, HNSCC: Head and neck squamous cell carcinoma, TAM: tumor-associated macrophages, NK: natural killer cells, DC: dendritic cells, IL: interleukin, Treg: regulatory T cell, TNF: tumor necrosis factor, TGF: transforming growth factor.

See this image and copyright information in PMC

References

1. Mody M.D., Rocco J.W., Yom S.S., Haddad R.I., Saba N.F. Head and neck cancer. Lancet. 2021;398:2289–2299. doi: 10.1016/S0140-6736(21)01550-6. - DOI - PubMed
1. Chaturvedi A.K., Engels E.A., Pfeiffer R.M., Hernandez B.Y., Xiao W., Kim E., Jiang B., Goodman M.T., Sibug-Saber M., Cozen W., et al. Human Papillomavirus and Rising Oropharyngeal Cancer Incidence in the United States. J. Clin. Oncol. 2011;29:4294–4301. doi: 10.1200/JCO.2011.36.4596. - DOI - PMC - PubMed
1. Pike L.R., Royce T.J., Mahal A.R., Kim D.W., Hwang W.L., Mahal B.A., Sanford N.N. Outcomes of HPV-Associated Squamous Cell Carcinoma of the Head and Neck: Impact of Race and Socioeconomic Status. J. Natl. Compr. Cancer Netw. 2020;18:177–184. doi: 10.1200/JCO.2019.37.15_suppl.e18103. - DOI - PMC - PubMed
1. Carlander A.F., Jakobsen K.K., Bendtsen S.K., Garset-Zamani M., Lynggaard C.D., Jensen J.S., Grønhøj C., von Buchwald C. A Contemporary Systematic Review on Repartition of HPV-Positivity in Oropharyngeal Cancer Worldwide. Viruses. 2021;13:1326. doi: 10.3390/v13071326. - DOI - PMC - PubMed
1. Doorbar J., Quint W., Banks L., Bravo I.G., Stoler M., Broker T.R., Stanley M.A. The Biology and Life-Cycle of Human Papillomaviruses. Vaccine. 2012;30((Suppl. 5)):F55–F70. doi: 10.1016/j.vaccine.2012.06.083. - DOI - PubMed

Publication types

Actions

LinkOut - more resources

Full Text Sources

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Novel Immunotherapeutic Approaches to Treating HPV-Related Head and Neck Cancer

Affiliations

Novel Immunotherapeutic Approaches to Treating HPV-Related Head and Neck Cancer

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

LinkOut - more resources

Full Text Sources