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Oropharyngeal Squamous Cell Carcinoma Morphology and Subtypes by Human Papillomavirus Type and by 16 Lineages and Sublineages

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Abstract

Oropharyngeal squamous cell carcinoma (SCC) is increasing in incidence and, in Western countries, strongly associated with transcriptionally-active high-risk human papillomavirus (HPV). Within HPV-positive tumors, there is wide morphologic diversity with numerous histologic subtypes of SCC. There are also variable degrees of keratinization, anaplasia, stromal fibrosis, and maturing squamous differentiation. Unlike in the uterine cervix, where associations between HPV types and lineages/sublineages within types have been investigated with some clear correlations identified, little to no data exists for oropharyngeal SCC. In this study, for a large cohort of oropharyngeal SCC patients, we performed RTPCR for high-risk HPV. For the HPV positive patients, we sequenced the DNA of the entire HPV16 genome and determined lineages and sublineages, correlating HPV status, genotype, and HPV16 lineages/sublineages with SCC subtype and various histologic features. Of the 259 patients, 224 (86.5%) were high-risk HPV positive, of which 210/224 (93.8%) were HPV type 16 and 6/224 (2.7%) HPV type 33. Of the four HPV16 lineages, A was the most frequent (192/214 or 89.8%) and of the HPV16 A sublineages, A1 was the most frequent (112/210 or 53.3%). Patients with HPV negative tumors were more often keratinizing vs other types (23/35 or 65.7%) and thus more likely to have more maturing squamous differentiation and stromal desmoplasia. There was no significant correlation between HPV type (16 versus other), between HPV16 lineage (A versus others), or HPV16 A sublineages (A1 or A2 versus others) and morphologic type of SCC nor the various morphologic features of anaplasia/multinucleation, degree of keratinization, nor amount of stromal desmoplasia. In summary, in our cohort, there was no correlation between the type of HPV, the HPV 16 lineage or sublineage, and any of the histologic features or morphologic SCC subtypes.

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Acknowledgements

We would like to acknowledge the Translational Pathology Shared Resource (TPSR) at Vanderbilt University Medical Center which is supported by NCI/NIH Cancer Center Support Grant 5P30 CA68485-19 and the Vanderbilt Mouse Metabolic Phenotyping Center Grant 2 U24 DK059637-16. This work was also supported by funds from the NIH Grant R01DE026471 (Wang) and by funds from the intramural research program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH (Mirabello).

Funding

Research was performed using the Translational Pathology Shared Resource (TPSR) at Vanderbilt University Medical Center which is supported by NCI/NIH Cancer Center Support Grant 5P30 CA68485-19 and the Vanderbilt Mouse Metabolic Phenotyping Center Grant 2 U24 DK059637-16. This work was supported by funds from the NIH grant R01DE026471 (Wang), and also by funds from the intramural research program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH (Mirabello).

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Authors and Affiliations

  1. Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Vanderbilt University Hospital, Room 3020D 1121 Medical Center Drive, Nashville, TN, 37232-2561, USA

    James S. Lewis Jr. & Mitra Mehrad

  2. Department of Otolaryngology – Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

    James S. Lewis Jr. & Krystle A. Lang-Kuhs

  3. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA

    Lisa Mirabello, Maisa Pinheiro, Meredith Yeager, Joseph F. Boland, Michael Cullen, Mia Steinberg & Sara Bass

  4. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA

    Ping Liu

  5. Department of Pharmacology and Regenerative Medicine, The University of Illinois at Chicago, Chicago, IL, USA

    Xiaowei Wang

  6. Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA

    William D. Dupont & W. Dale Plummer

  7. Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc, Frederick, MD, USA

    Meredith Yeager, Joseph F. Boland, Michael Cullen, Mia Steinberg & Sara Bass

  8. Department of Otolaryngology, Head and Neck Surgical Oncology, Massachusetts Eye and Ear, Boston, MA, USA

    Connor O’Boyle, Maoxuan Lin & Daniel L. Faden

  9. Massachusetts General Hospital, Boston, MA, USA

    Daniel L. Faden

  10. Harvard Medical School, Boston, MA, USA

    Daniel L. Faden

  11. Department of Epidemiology, University of Kentucky College of Public Health, Lexington, KY, USA

    Krystle A. Lang-Kuhs

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  1. James S. Lewis Jr.
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  2. Lisa Mirabello
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  3. Ping Liu
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  4. Xiaowei Wang
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  8. Meredith Yeager
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  10. Michael Cullen
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  12. Sara Bass
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  13. Mitra Mehrad
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  14. Connor O’Boyle
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  15. Maoxuan Lin
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  16. Daniel L. Faden
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  17. Krystle A. Lang-Kuhs
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Corresponding author

Correspondence to James S. Lewis Jr..

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The authors declare that they have no conflicts of interest as it relates to this research.

Ethical Approval

This study was performed with approval of the respective institutional review boards and complies with required ethical standards. Given the retrospective nature of the study, patients were never contacted, and we did not require informed consent.

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Lewis, J.S., Mirabello, L., Liu, P. et al. Oropharyngeal Squamous Cell Carcinoma Morphology and Subtypes by Human Papillomavirus Type and by 16 Lineages and Sublineages. Head and Neck Pathol 15, 1089–1098 (2021). https://doi.org/10.1007/s12105-021-01318-4

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  • DOI: https://doi.org/10.1007/s12105-021-01318-4

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