What is HPV?
HPV stands for human papillomavirus. It is the most common sexually transmitted infection in the US. It is a very ancient virus, as old as modern humans. Annually, about 14 million new genital HPV infections occur, and nearly all sexually active men and women will be infected with HPV at some point in their lives.
There are more than 200 known HPV types, and many more are presently uncharacterized, especially in the oral cavity. HPV types are classified as cutaneous or mucosal types depending on what the HPV infects: either the skin or the mucus. About 40 HPV types are infecting the genital area. Of these 40 mucosal HPV types, they are further characterized as low-risk or high-risk HPV types, based on their association with cancer development. There are at least 14 high-risk HPV types identified so far. HPV 16 and HPV 18 represent approximately 70% of high-risk HPV infections.
In the majority of cases, an HPV infection does not cause any visible symptoms. In healthy individuals, about 50% of new HPV infections are cleared naturally by the body (without any treatment) within 6 months time, and 90% of HPV infections will be cleared within 2 years. Low-risk HPV infection can cause genital warts, and high-risk HPV infection can lead to tumor development in a minority of individuals (<5%). E6 and E7 proteins encoded by high-risk HPV types are oncogenes, they can inactivate tumor suppressor genes p53 and pRb respectively, which initiates the development of a tumor.
HPV is mainly transmitted through sexual contact: vaginal, anal, or oral sex. Upon initiation of sexual activity, about 40% women become positive for HPV infection in 24 months. A small fraction of HPV infection can be transmitted through hand-to-genital or other skin-to-skin contact. It is reported that about 1% of virgins are positive for HPV infection and about 10% virgins reporting non-penetrating sex are positive for HPV infection. Because most incidences of HPV infection are asymptomatic, most people do not know whether they are infected with HPV or not, and only molecular assays can determine the presence of HPV infection. Although the body can clear an HPV infection, a small fraction of HPV remains in the body and dormant. This dormant HPV can be re-activated even 10-20 years later when our body’s immune system is weakened as part of a normal aging process.
Use of a condom or a dental dam can reduce the risk of HPV infection, but cannot fully protect one from HPV infection, because HPV can infect skin that remains uncovered during sexual activity.
The best way to prevent HPV infection proactively is through an HPV vaccine–before a person becomes sexually active. The FDA-approved Gardasil covers four HPV types: HPV 6, 11, 16, and 18. HPV 6 and 11 are low-risk HPV types, and can cause genital warts; while HPV 16 and 18 are high-risk HPV types, and are responsible for 70% of cervical cancer cases. The HPV vaccine is highly effective in preventing HPV infection as well as the development of genital warts and cervical precancer lesions. However, HPV vaccine is prophylactic, thus it does not provide protection for individuals who are already exposed to HPV. The protection gained from the HPV vaccine is type-specific; it does not provide protection of infection of other HPV types besides these four HPV types.
Persistent HPV Infection Increases Risk of Cancer
HPV is the most common sexually transmitted infection. Almost every adult will be exposed to HPV infection in his/her lifetime. Yet, only a small fraction of HPV infected individuals have increased risk of developing cancer. Currently, there is no diagnostic test that can accurately identify such individuals, expect routine HPV testing.
Although most of us with a healthy immune system can clear HPV infection within 6-24 months, HPV virus can remain latent in our body for many years. These dormant HPV viruses can strike back when our immune system is weakened. These reactivated HPV infections are indistinguishable from newly acquired HPV infections. Currently, there is no diagnostic test that can accurately determine who and when a latent HPV infection will reactivate, only routine HPV testing can.
- People who are engaged in risky sexual behaviors are at an increased risk of having persistent HPV infection
- Early age of sexual activity
- Increased number od lifetime sexual partners
- Unprotected sex and sexual contact
- People who have weakened immune systems are at an increased risk of having persistent HPV infection
- Tobacco smoking
- People with certain genetic predisposition are at an increased risk of having persistent HPV infection
- Family history of persistent genital HPV infection and cervical lesions
HPV infects stratified epithelium cells and requires micro-abrasion to reach basal layer cells. Once infected, various HPV proteins are expressed in cells in different layers of the epithelium. Mature HPV viral particles are assembled at the top layer, then released and are then ready infect new cells.
High-risk HPV viruses encode two oncogenes, E6 and E7, that inactivate the two most important tumor suppressor genes in cells: p53 and pRb. Without these two tumor suppressor genes, the cell continues to accumulate additional mutations, ultimately leading to malignant transformation.