By Jason Wasserman MD PhD FRCPC
July 31, 2024
HPV associated dysplasia of the larynx is a precancerous condition in which the squamous cells that cover the inside surface of the larynx begin to show abnormal growth due to infection with the human papillomavirus (HPV). If not treated effectively, this condition can progress to a type of laryngeal cancer called squamous cell carcinoma. This condition can affect any part of the larynx, although an area of the larynx called the glottis is most commonly affected.
Patients with HPV associated dysplasia may not notice any symptoms early in the disease. However, as the disease progresses, common symptoms include hoarseness (a change in the quality of the voice), throat pain, difficulty swallowing, persistent cough, and difficulty breathing.
HPV associated dysplasia of the larynx is caused by chronic (long-standing) infection with certain types of HPV, particularly the high-risk variants 16 and 18. These variants also cause squamous cell carcinoma of the oropharynx, cervix, and anal canal. HPV infects the squamous cells of the larynx and induces changes that can lead to dysplasia.
The diagnosis of HPV associated dysplasia in the larynx is typically made through a biopsy of the affected tissue. This sample is examined under a microscope to assess the presence and degree of dysplasia. Additionally, the presence of high-risk HPV RNA or DNA may be confirmed through molecular testing tests such as in situ hybridization (ISH) or polymerase chain reaction (PCR).
Microscopically, HPV associated dysplasia is characterized by abnormalities in the squamous cells that cover the inside surface of the larynx. These abnormalities include pleomorphism (variation and nuclear size and shape), increased nuclear-to-cytoplasmic ratio, hyperchromatic nuclei, and possibly increased mitotic activity. The architectural organization of epithelium may also be disrupted. Pathologists often describe this type of dysplasia as nonkeratinizing because the abnormal squamous cells have not undergone a process called keratinization. This makes the abnormal squamous cells appear blue when examined under the microscope. In contrast, HPV independent squamous dysplasia looks pinker as the cells typically undergo keratinization.
Unlike HPV-independent dysplasia, HPV associated dysplasia of the larynx is not graded because grade has not been shown to accurately correlate with the risk of developing cancer.
p16 is a protein that is commonly overexpressed in cells affected by high-risk variants of HPV. Pathologists test for p16 as a biomarker for HPV associated dysplasia and cancers because its presence strongly correlates with HPV infection. Overexpression of p16 in the cells of a biopsy is used to support the diagnosis of HPV-related pathology. The p16 test can be particularly useful as it helps differentiate HPV-associated lesions from other conditions that are not related to HPV.
Currently, there is not enough evidence for doctors to accurately predict the risk of developing cancer in patients with HPV associated dysplasia of the larynx. However, the limited data available suggests that the risk is lower compared to patients with HPV independent dysplasia.
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