Human Papillomavirus, or HPV, is a widespread virus. For most people, an infection is temporary and resolves without health issues. However, a persistent infection with a “high-risk” type of HPV is linked to the development of several cancers. The virus’s ability to cause disease stems from specific proteins it produces after infecting human cells.
Two proteins, E6 and E7, are the primary drivers of cancer development. These oncoproteins interfere with the normal functions of infected cells, creating an environment for viral replication. In doing so, they can initiate a cascade of events that leads to malignant transformation. Understanding the roles of E6 and E7 explains how an HPV infection can progress to cancer.
The Function of HPV Oncoproteins E6 and E7
Human cells have built-in safety mechanisms to prevent cancer that monitor cell division and health. If a cell becomes damaged or divides uncontrollably, these systems can halt the process or trigger a self-destruct sequence called apoptosis. Two proteins in this defense network are p53 and the retinoblastoma protein (pRb), which function as tumor suppressors to stop abnormal growth.
The E6 and E7 oncoproteins from high-risk HPV directly target these cellular guardians. The primary job of the E6 oncoprotein is to neutralize p53 by marking it for destruction. This action removes the brakes on cell death. Without p53, a cell with genetic errors loses its ability to undergo apoptosis and can continue to divide.
Simultaneously, the E7 oncoprotein targets the retinoblastoma protein, pRb. The function of pRb is to control the cell cycle, preventing division until it is appropriate. E7 binds to and inactivates pRb, forcing the cell into a state of continuous replication. The combined actions of E6 and E7 disable the cell’s self-destruct mechanism while forcing it to multiply, paving the way for uncontrolled growth.
How E6 and E7 Drive Cancer Development
With p53 and pRb neutralized by E6 and E7, cells begin to divide without restraint. This constant replication is error-prone, and without a functional p53 to halt the process, genetic mutations accumulate rapidly. The cell’s genome becomes increasingly unstable, leading to further abnormalities in genes that regulate growth and survival.
This accumulation of genetic damage first leads to precancerous conditions, known as dysplasia or intraepithelial lesions. In these lesions, the cells appear abnormal but have not yet invaded surrounding tissues. For cervical cancer, this is seen as cervical intraepithelial neoplasia (CIN), which is graded by severity. The persistent expression of E6 and E7 drives the progression from low-grade to high-grade lesions.
If the infection persists and E6 and E7 are expressed over many years, the genetic damage can lead to a malignant cell. This cell can break through the initial tissue layer and invade deeper structures, establishing an invasive cancer. While this process is associated with cervical cancer, the same mechanism drives other HPV-associated cancers, including:
- Oropharynx (throat)
- Anus
- Vulva
- Vagina
- Penis
Testing for Active E6 and E7 Expression
Diagnosing HPV-related risks involves more than just detecting the virus’s presence. A standard HPV DNA test identifies the genetic material of high-risk HPV types. However, a positive DNA test only indicates an infection and not what the virus is doing within the cells. Many high-risk HPV infections are transient and cleared by the immune system without causing cellular changes.
A more specific test, the HPV E6/E7 mRNA test, provides a clearer picture of immediate risk. This test detects messenger RNA (mRNA) from the E6 and E7 genes, not the virus’s DNA. The presence of E6/E7 mRNA is direct evidence that the viral genes are active and producing oncoproteins. This test helps distinguish a simple HPV presence from an infection actively progressing towards cancer, providing a more accurate risk assessment.
Interpreting E6/E7 Test Results
The results of an HPV E6/E7 mRNA test have direct implications for patient management. A positive result indicates a higher risk of having or developing high-grade precancerous lesions compared to a positive HPV DNA test alone. This finding prompts more immediate follow-up to assess the extent of any existing abnormalities.
For individuals with a positive E6/E7 mRNA test, the next step is often a colposcopy. This procedure allows a provider to visually examine the cervix or other areas under magnification. A vinegar-like solution is applied to highlight abnormal areas, which may then be biopsied. The tissue samples are then examined by a pathologist to determine the grade of any precancerous changes.
A positive E6/E7 test is not a diagnosis of cancer but a risk indicator that helps guide clinical decisions. It allows for earlier intervention in those with the highest risk of progression. This targeted approach aims to identify and treat precancerous lesions before they can develop into invasive cancer.