Human Papillomavirus (HPV) is a highly common infection, comprising over 200 related viruses. The virus is primarily transmitted through intimate skin-to-skin contact, making it the most prevalent sexually transmitted infection globally. Most people infected with HPV never know they have it, as the immune system typically clears the virus naturally within one to two years. However, a small subset of HPV types are classified as high-risk because they can persist for years and cause abnormal cellular changes, leading to the development of various cancers.
Identifying the High-Risk Types
Only a fraction of HPV types are known to cause cancer; these are collectively referred to as oncogenic, or high-risk, types. There are approximately 12 high-risk types, but HPV 16 and HPV 18 are the most significant contributors, causing about 70% to 80% of all HPV-associated cancers worldwide. The classification as high-risk is based on their ability to interfere with normal cellular growth and division. The other high-risk types include HPV 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59. Persistent infection with these types increases the potential for precancerous lesions to develop over time, distinguishing them from low-risk types like HPV 6 and 11, which cause genital warts.
Cancer Development Pathways
The progression from a persistent high-risk HPV infection to cancer is a slow process requiring the virus to hijack the host cell’s regulatory machinery. This oncogenic process is driven by two specific viral proteins, E6 and E7, produced by the high-risk HPV strains. Continuous expression of E6 and E7 defines a persistent and potentially cancerous infection.
The E6 protein targets the cellular tumor suppressor protein p53, marking it for degradation. The p53 protein normally halts cell division or initiates programmed cell death (apoptosis) when a cell is damaged. By destroying p53, E6 removes a primary cellular safeguard against genetic instability and mutation.
In parallel, the E7 protein binds to and inactivates the retinoblastoma protein (pRb), another powerful tumor suppressor. The pRb protein normally prevents the cell from progressing through the cell cycle and dividing. By disabling pRb, E7 forces the cell into continuous, unregulated proliferation.
This dual assault allows the infected cell to divide indefinitely, accumulating the genetic damage necessary for malignant transformation. While cervical cancer is the most common association, high-risk HPV is also responsible for the majority of anal cancers, as well as a significant portion of vaginal, vulvar, penile, and oropharyngeal cancers. Cancer development typically occurs only after years, sometimes decades, of persistent infection and the gradual accumulation of pre-cancerous lesions known as dysplasia.
Screening and Detection Methods
Screening programs focus on identifying high-risk HPV infections and the abnormal cellular changes they cause before cancer can develop. The two main tools for cervical cancer screening are the Pap test and HPV DNA testing. The Pap test, or cytology, involves collecting cells from the cervix and examining them under a microscope to look for abnormal or pre-cancerous cells.
The HPV DNA test directly detects the genetic material of the high-risk HPV types in a cervical sample, confirming the presence of the cancer-causing virus. For individuals over the age of 30, guidelines often recommend “co-testing,” which involves performing both the Pap test and the HPV test simultaneously to maximize detection sensitivity. Primary HPV screening, which uses the HPV DNA test as the first-line screen, is becoming the preferred method for people aged 25 and older.
A positive HPV test or an abnormal Pap test result does not mean cancer is present, but it does signal a need for further evaluation. Follow-up procedures, such as colposcopy, allow a healthcare provider to use a specialized magnifying instrument to closely examine the cervix for any suspicious areas. If pre-cancerous lesions are confirmed during this examination, they can be removed with highly effective, minimally invasive treatments, preventing progression to invasive cancer.
Vaccination as Primary Prevention
Vaccination represents the most proactive and effective strategy to prevent infection by the high-risk HPV strains. The current vaccine, Gardasil 9, is designed to protect against nine types of HPV. This includes the two highest-risk types, HPV 16 and 18, and five of the other high-risk oncogenic types: HPV 31, 33, 45, 52, and 58.
The vaccine works by generating an immune response to the viral surface proteins, ensuring the body can recognize and neutralize the virus before it can establish a persistent infection. Routine vaccination is recommended for pre-teens, typically starting at age 11 or 12, because the vaccine provides the strongest protection when administered before any exposure to the virus has occurred.
Individuals who start the series before age 15 require only two doses, spaced six to twelve months apart, due to their robust immune response. Those who begin the series later, between ages 15 and 26, generally require three doses over a six-month period. The vaccine is also approved for some adults up to age 45, following a discussion with a healthcare provider about potential benefit.