# Detection of Human Papillomavirus (HPV) in HPV-Associated Oropharyngeal Squamous Cell Carcinoma: A Review of Diagnostic Approach and Its Importance for the Head and Neck Oncologist

**Authors:** Amanda J. Bastien, Daniel Manzoor, Evan S. Walgama, Kevin S. Scher, Julie K. Jang, Justin Moyers, Zachary S. Zumsteg, Allen S. Ho, Jon Mallen-St. Clair

PMC · DOI: 10.3390/cancers18010056 · Cancers · 2025-12-24

## TL;DR

This paper reviews methods to detect HPV in oropharyngeal cancer and emphasizes its importance for accurate diagnosis and treatment.

## Contribution

The paper provides a comprehensive review of current and emerging diagnostic techniques for HPV-associated oropharyngeal cancer.

## Key findings

- Multiple histopathologic techniques like immunohistochemistry and in situ hybridization are used to detect HPV in oropharyngeal cancer.
- Professional organizations have developed guidelines for diagnosing HPV-associated oropharyngeal squamous cell carcinoma.
- Newer methods like liquid biopsy may enhance future diagnosis and cancer surveillance.

## Abstract

The incidence of Oropharyngeal Squamous Cell Carcinoma is increasing in the United States, largely due to the human papillomavirus. Understanding the histopathologic assessment for oropharyngeal squamous cell carcinoma, including the identification of the human papilloma virus (HPV), is essential for successful prognostication and treatment. Several histopathologic techniques are now available for the identification of HPV-associated Oropharyngeal Squamous Cell Carcinoma. These techniques include immunohistochemistry, in situ hybridization and newer approaches such as the liquid biopsy. These variable techniques and approaches have prompted the development of practice guidelines by multiple professional organizations, including the National Comprehensive Cancer Network, the American Society of Clinical Oncology, and the College of American Pathologists. This paper reviews and discusses these guidelines and the current literature surrounding HPV-Associated Oropharyngeal Cancer. Understanding the tumor histopathology is essential for the head and neck oncologist and will better inform multidisciplinary discussions so patients receive maximal patient-centered care.

Introduction: Histopathologic assessment of surgical specimens imparts crucial information that is essential for diagnosis, treatment planning and prognostication for patients with Oropharyngeal Squamous Cell Carcinoma (OPSCC). This review explores the range of diagnostic techniques utilized to assess the HPV (Human Papilloma Virus) status in OPSCC. It covers both traditional methods—such as p16 immunohistochemistry, HPV in situ hybridization, and DNA polymerase chain reaction (PCR)—and newer, evolving strategies including circulating HPV tumor DNA analysis and oral HPV DNA/mRNA PCR testing. Discussion: There are currently several histopathologic techniques for the diagnosis of HPV-associated OPSCC. This complexity of care has led to guidelines from numerous authorities (NCCN, ASCO, CAP), which this paper discusses and summarizes for head and neck oncology specialists. Conclusion: The ability to detect HPV in HPV-associated OPSCC is imperative for diagnosis, prognostication, staging, and management of the disease. Advances including liquid biopsy (TTMV-HPV DNA) may be utilized as an adjunct to diagnosis, treatment, and cancer surveillance in the future.

## Linked entities

- **Proteins:** CDKN2A (cyclin dependent kinase inhibitor 2A)
- **Diseases:** Oropharyngeal Squamous Cell Carcinoma (MONDO:0044704)

## Full-text entities

- **Genes:** CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029] {aka ARF, CAI2, CDK4I, CDKN2, CMM2, INK4}
- **Diseases:** OPSCC (MESH:D000077195), cancer (MESH:D009369)
- **Species:** Homo sapiens (human, species) [taxon 9606], Human papillomavirus (species) [taxon 10566]

## Full text

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## Figures

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## References

79 references — full list in the complete paper: https://tomesphere.com/paper/PMC12784711/full.md

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Source: https://tomesphere.com/paper/PMC12784711