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Human Papillomavirus-Associated Oral Cavity Squamous Cell Carcinoma: An Entity with Distinct Morphologic and Clinical Features

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Abstract

Background

HPV-associated oral cavity squamous cell carcinoma (SCC) is not well-characterized in the literature, and also has a clinical significance that is poorly understood.

Methods

We gathered a cohort of oral cavity (OC) SCC with nonkeratinizing morphology, either in the invasive or in situ carcinoma (or both), tested for p16 by immunohistochemistry and high risk HPV E6/E7 mRNA by RTPCR (reference standard for transcriptionally-active high risk HPV) and gathered detailed morphologic and clinicopathologic data.

Results

Thirteen patients from two institutions were proven to be HPV-associated by combined p16 and high risk HPV mRNA positivity. All 13 patients (100%) were males, all were heavy smokers (average 57 pack/year), and most were active drinkers (9/11 or 81.8%). All 13 (100%) involved the tongue and/or floor of mouth. All had nonkeratinizing features, but maturing squamous differentiation varied widely (0–90%; mean 37.3%). Nonkeratinizing areas had high N:C ratios and larger nests, frequently with pushing borders, and minimal (or no) stromal desmoplasia. The carcinoma in situ, when present, was Bowenoid/nonkeratinizing with cells with high N:C ratios, full thickness loss of maturation, and abundant apoptosis and mitosis. HPV was type 16 in 11 patients (84.6%) and type 33 in two (15.4%). Nine patients had treatment data available. These underwent primary surgical resection with tumors ranging from 1.6 to 5.2 cm. Most had bone invasion (6/9–66.7% were T4a tumors), and most (6/9–66.7%) had extensive SCC in situ with all 6 of these patients having final margins positive for in situ carcinoma.

Conclusions

HPV-associated OCSCC is an uncommon entity that shows certain distinct clinical and pathologic features. Recognition of these features may help pathologic diagnosis and could potentially help guide clinical management.

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Data Availability

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Funding

Research was performed using discretionary funds from the Department of Pathology, Microbiology, and Immunology. The work also utilized 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 Shared Instrumentation Grant S10 OD023475. This work was supported by funds from the NIH Grant R01DE026471 (Wang). This work was also supported by the National Cancer Institute (NCI) K07CA218247 (PI: Krystle Kuhs); Vanderbilt Clinical Oncology Research Career Development Program (K12 CA090625); and the Vanderbilt Institute for Clinical and Translational Research (UL1 TR000445 from NCATS/NIH). This work was supported by funds from the NIH Grant U24 DK059637-16.

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Authors and Affiliations

  1. Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, 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.

  3. Department of Pathology, University of Kentucky, Lexington, KY, USA

    Molly H. Smith

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

    Xiaowei Wang & Fangjia Tong

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

    Krystle A. Lang-Kuhs

  6. Markey Cancer Center, University of Kentucky, Lexington, KY, USA

    Krystle A. Lang-Kuhs

  7. 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.

Authors
  1. James S. Lewis Jr.
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  2. Molly H. Smith
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  3. Xiaowei Wang
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  4. Fangjia Tong
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  5. Mitra Mehrad
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  6. Krystle A. Lang-Kuhs
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Contributions

All authors whose names appear on the submission made substantial contributions to the conception or design of the work, to the acquisition, analysis, or interpretation of data, and/or drafted the work or revised it critically for important intellectual content including approving the version to be published. They agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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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 work.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was performed with approval of the respective institutional review boards of Vanderbilt University Medical Center and the University of Kentucky and complies with required ethical standards. Given the retrospective nature of the study, with consultation with the institutional review boards, it was determined that the study did not need ethical approval. Patients were never contacted, and we did not require informed consent or specific consent to publish.

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Lewis, J.S., Smith, M.H., Wang, X. et al. Human Papillomavirus-Associated Oral Cavity Squamous Cell Carcinoma: An Entity with Distinct Morphologic and Clinical Features. Head and Neck Pathol 16, 1073–1081 (2022). https://doi.org/10.1007/s12105-022-01467-0

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