p16

p16 is a protein produced by many cells in the body. It plays an important role in regulating how cells grow and divide. Because it helps prevent cells from growing uncontrollably, p16 is known as a tumor suppressor protein. When cells lose control of their growth, it can lead to cancer. Pathologists often test for p16 because high levels of this protein are commonly seen in certain types of cancer, especially those linked to infection with human papillomavirus (HPV).

What types of normal cells and tissues express p16?

Under normal conditions, p16 is made by many different types of cells throughout the body. It is usually produced in small amounts, just enough to help control cell growth. Most of the p16 protein is located in the nucleus, the part of the cell that contains DNA, although smaller amounts can also be found in the cytoplasm, which surrounds the nucleus.

How do pathologists test for p16?

Pathologists test for p16 using a laboratory method called immunohistochemistry (IHC). In this test, special antibodies are applied to a thin slice of tissue on a glass slide. If the p16 protein is present, the antibodies bind to it, causing a visible colour change that can be observed under the microscope. The pathologist then determines whether the staining is positive (meaning p16 is present) or negative (meaning it is absent). If the staining is positive, they may also describe whether the staining is strong and diffuse (involving most of the tumor cells), which is especially important for cancers associated with HPV.

What types of tumours express p16?

Several types of tumours commonly show high levels of p16. These include:

HPV-related precancerous and cancerous tumours:

• Cervical squamous intraepithelial lesions (SIL)
• Cervical adenocarcinoma in situ (AIS)
• Usual vulvar, vaginal, and penile intraepithelial neoplasia (VIN, VAIN, PeIN)
• Squamous cell carcinoma of the anogenital region and oropharynx (throat)

Other p16-positive tumours:

• Some squamous cell carcinomas of the esophagus and bladder
• Endocervical adenocarcinoma
• Uterine serous carcinoma
• High-grade serous carcinoma of the ovary, fallopian tube, or peritoneum
• Some malignant mixed Müllerian tumours (carcinosarcomas) and undifferentiated carcinomas of the female reproductive tract

Why is p16 important in a pathology report?

Testing for p16 helps pathologists make an accurate diagnosis and guide treatment decisions. The presence and pattern of p16 staining can provide useful information in several ways:

• To confirm HPV-related tumours: Cancers caused by HPV often show strong, widespread (diffuse) p16 staining. This is helpful for confirming a diagnosis of cervical or oropharyngeal cancer and can also provide information about how the tumour might behave and respond to treatment.

• To distinguish between similar tumour types: Even in tumours not caused by HPV, p16 testing can help pathologists differentiate between cancers that look similar under the microscope but behave differently.

Overall, the results of a p16 test add valuable information that can help doctors choose the most appropriate and effective treatment for each patient.

Questions to ask your doctor

• What does the p16 result mean in my pathology report?

• Does the presence of p16 suggest that my tumour is caused by HPV?

• Will the p16 result affect my treatment or follow-up plan?

• Are additional tests needed to confirm the diagnosis?

• Is p16 testing useful for monitoring my condition in the future?