by Jason Wasserman MD PhD FRCPC
April 10, 2026
HPV-associated dysplasia of the oral cavity is a precancerous condition in which the cells lining the inside of the mouth develop abnormal features due to infection with the human papillomavirus (HPV). The word dysplasia means that the cells have started to grow and behave abnormally — they are not cancer yet, but without treatment, they can progress to a type of oral cancer called squamous cell carcinoma over time.
Receiving this diagnosis means that an abnormal area was found in your mouth, a biopsy was taken, and the pathologist has identified precancerous changes driven by HPV. This is a serious finding that warrants treatment, but it is not cancer. When precancerous changes like these are identified and treated before they progress, the outcome is generally excellent.
What is HPV and how does it cause dysplasia?
HPV is a very common virus that infects squamous cells — the flat cells that line the surfaces of the mouth, throat, genitals, and other sites in the body. There are more than 100 types of HPV. Most cause no lasting harm and are cleared by the immune system on their own. However, certain high-risk types — particularly HPV 16 and HPV 18 — can persist in cells and disrupt the normal mechanisms that regulate cell growth and division.
Specifically, high-risk HPV produces proteins that block the function of tumor-suppressor proteins — the molecular brakes that normally prevent cells from dividing out of control. When these brakes are disrupted, cells begin to grow abnormally, and over time this can lead to dysplasia and eventually cancer. This is the same mechanism by which high-risk HPV causes precancerous changes in the oropharynx, cervix, and anal canal.
HPV is spread through direct skin-to-skin contact, including sexual contact and oral-genital contact. It is one of the most widespread viruses in the world — most sexually active adults will have at least one HPV infection during their lifetime. The vast majority of infections clear without causing any lasting changes. HPV-associated dysplasia of the oral cavity develops only in a small subset of people with persistent infection with a high-risk type.
What are the symptoms?
Many people with HPV-associated dysplasia of the oral cavity have no symptoms at all, particularly in the early stages. This is one of the reasons regular dental and medical checkups are valuable — the condition may be identified before it causes any noticeable problems.
When symptoms are present, they may include:
- A red, white, or mixed red-and-white patch inside the mouth that does not go away.
- A slightly raised or thickened area of tissue on the tongue, floor of the mouth, or inner cheek.
- Mild pain, tenderness, or a burning sensation in the affected area.
- Difficulty swallowing, if the lesion is large or in an awkward location.
Any patch or sore in the mouth that has not healed within two to three weeks should be evaluated by a dentist or doctor.
How is the diagnosis made?
The diagnosis is made by a pathologist after a tissue sample is removed from the abnormal area. A doctor or dentist who notices an unusual patch or lesion in the mouth will perform a biopsy — a small procedure in which a sample of tissue is taken and sent to the pathology laboratory for examination.
In the laboratory, the pathologist examines the tissue under the microscope to assess the degree of cellular abnormality. In most cases, additional testing is performed to confirm that the dysplasia is driven by HPV rather than by other causes such as tobacco. These tests include:
- p16 immunohistochemistry. This test detects a protein called p16, which is produced in large amounts by cells infected with high-risk HPV. Strong, widespread p16 staining in dysplastic cells supports a diagnosis of HPV-associated dysplasia.
- In situ hybridization (ISH) or PCR. In situ hybridization and polymerase chain reaction (PCR) are molecular tests that detect HPV DNA or RNA directly within the tissue. These tests confirm the presence of the virus in the abnormal cells and can identify the specific HPV type.
What does the pathology report describe?
Microscopic appearance
Under the microscope, HPV-associated dysplasia of the oral cavity has a distinctive appearance. The squamous cells in the affected area show a range of abnormal features, including:
- Pleomorphism. Pleomorphism means variation in the size and shape of cells. Normal squamous cells are relatively uniform in appearance; in dysplasia, the cells look uneven and irregular.
- Hyperchromatic nuclei. The nuclei — the control centers of the cells that contain the DNA — appear darker than normal. Pathologists call this hyperchromasia. It reflects abnormal DNA activity in the cells.
- Increased mitotic activity. More cells than usual are dividing, a finding called increased mitotic activity. This is a sign that the cells are growing more rapidly than normal.
- Nonkeratinizing appearance. HPV-associated dysplasia is typically described as nonkeratinizing, meaning the abnormal cells have not undergone keratinization — a process by which cells produce a tough protein called keratin. Because of this, the cells appear blue or basaloid under the microscope rather than the pink color seen in HPV-independent dysplasia. This nonkeratinizing appearance is one of the features that helps the pathologist distinguish HPV-associated dysplasia from other types of oral dysplasia.
- Disrupted architecture. The normal organized layering of squamous cells in the epithelium is disturbed, with abnormal cells found throughout rather than being neatly arranged from base to surface.
Grading
Unlike HPV-independent dysplasia, HPV-associated dysplasia of the oral cavity is not assigned a grade (mild, moderate, or severe). Research has shown that grading does not reliably predict cancer risk in HPV-associated lesions. For this reason, the focus is on the presence of the dysplasia itself — and on whether it has been completely removed — rather than on a specific grade.
p16 result
p16 is a protein that acts as a brake on cell division. When cells are infected by high-risk HPV, the virus disables this brake, causing p16 to accumulate in large amounts throughout the cell. Pathologists detect this accumulation using immunohistochemistry. A strong, widespread positive p16 result in the dysplastic cells supports the diagnosis of HPV-associated dysplasia. If your report says the dysplasia is “p16 positive,” this confirms the HPV connection and is an expected finding for this diagnosis.
Margin
The margin is the edge of the tissue that was removed. Margin status is particularly important for a precancerous condition because it indicates whether all abnormal cells were removed.
- Negative margin (clear margin). No dysplasia is found at the cut edge of the tissue. This means the abnormal area appears to have been completely removed and is associated with a significantly lower risk of progression to cancer.
- Positive margin. Dysplastic cells are present at the cut edge, meaning some abnormal tissue may have been left behind. Your doctor will discuss whether additional treatment is needed to ensure complete removal.
- Cannot be assessed. If the tissue was fragmented or if the biopsy was small, it may not be possible to reliably evaluate the margin. In this case, complete excision of the remaining lesion is usually recommended.
What is the risk of developing cancer?
HPV-associated dysplasia of the oral cavity is a precancerous condition, and without treatment it carries a real risk of progressing to squamous cell carcinoma over time. Studies to date suggest that approximately 10 to 15% of patients with this diagnosis will develop oral cavity cancer if the dysplasia is not completely removed.
Surgical excision — complete removal of the dysplastic area — is associated with a substantially lower risk of cancer and a better overall outcome. This is why complete removal with clear margins is the goal of treatment.
It is also worth knowing that HPV-associated oral cavity cancer, when it does develop, tends to respond better to treatment than HPV-independent oral cavity cancer. This is consistent with what is seen in HPV-associated cancers at other sites such as the oropharynx.
What happens next?
The primary treatment for HPV-associated dysplasia of the oral cavity is surgical removal — excision of the abnormal area with the goal of achieving clear margins. This is typically performed by an oral surgeon or a head and neck surgeon and is done as a minor procedure under local anesthesia in most cases.
After excision, follow-up is important. The specific schedule will depend on factors such as the margin status, the extent of the dysplasia, and your overall health and risk factors. In general:
- If the dysplasia was completely removed with clear margins, regular surveillance of the oral cavity is still recommended, since new dysplastic changes can develop over time in patients with persistent HPV infection.
- If margins were positive or the lesion was not fully removed, re-excision or additional treatment will likely be recommended.
- If the dysplasia recurs or if new lesions appear, repeat biopsy and further treatment may be needed.
Quitting smoking and reducing alcohol consumption — if applicable — are strongly recommended, as tobacco and alcohol are independent risk factors that can accelerate the progression of oral dysplasia to cancer.
For family members or close contacts who have not yet been vaccinated, it is worth knowing that the HPV vaccine is highly effective at preventing infection with the high-risk HPV types that cause dysplasia and cancer. While vaccination cannot treat an existing infection, it can protect uninfected individuals. Vaccination is most effective when given before exposure to HPV, typically in adolescence, but it is also recommended for adults up to age 26, and may benefit some adults up to age 45.
Questions to ask your doctor
- Was the dysplastic area completely removed, and what did the margins show?
- Do I need additional surgery or treatment?
- How often should I come back for follow-up checkups, and what will those involve?
- What symptoms should prompt me to contact you before my next scheduled visit?
- Are there lifestyle changes — such as stopping smoking or reducing alcohol — that would reduce my risk?
- Should my family members or sexual partners be aware of anything related to this diagnosis?
- Is HPV vaccination relevant for anyone in my household?
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