Human Papillomavirus (HPV) is a common group of small, double-stranded DNA viruses that specifically infect the epithelial cells of the skin and mucous membranes. Over 200 different genetically distinct types, or genotypes, of HPV have been identified, each assigned a number based on the sequence of its genome. These numerous types are responsible for a wide range of clinical outcomes, from common, harmless skin warts to certain cancers.
High-Risk Versus Low-Risk Classification
Scientists categorize the numerous HPV types primarily based on their potential to cause cellular changes that can lead to cancer, which is referred to as their oncogenic potential. This classification divides the viruses into two main groups: low-risk HPV types and high-risk HPV types. The distinction serves as a fundamental framework for clinical relevance, guiding screening and management strategies for infected individuals.
Low-risk types are generally associated with benign lesions, such as warts, which typically do not progress to malignancy. Conversely, high-risk types are those that can lead to persistent infections, which may eventually cause abnormal cell growth and the development of cancer over many years. This grouping is applied specifically to the approximately 40 HPV types that infect the genital and mucosal areas.
Low-Risk Types and Associated Conditions
Low-risk HPV types are responsible for the vast majority of benign growths on the skin and mucosal surfaces. The most clinically recognized low-risk types are Human Papillomavirus Type 6 and Type 11. These two genotypes are responsible for causing over 90% of all anogenital warts, also known as condylomata acuminata.
These warts are non-cancerous skin lesions that can appear on or around the genitals or anus, often presenting as small, flesh-colored bumps or cauliflower-like growths. While generally harmless, they can be a source of discomfort and psychological distress. Types 6 and 11 can also cause a rare condition called recurrent respiratory papillomatosis, where benign tumors develop in the respiratory tract, particularly in the larynx.
Other low-risk HPV types are responsible for common warts that appear on other areas of the body, such as the hands, feet, and knees. These cutaneous HPV types, like HPV Type 1 and Type 2, cause plantar warts and common skin warts, respectively, by infecting the squamous epithelial cells of the skin.
High-Risk Types and Cancer Development
The high-risk HPV types are the main concern for public health because of their established link to several types of cancer. There are about 12 to 14 genotypes classified as high-risk, with HPV Type 16 and Type 18 being the most significant. Together, HPV 16 and 18 are implicated in approximately 70% of all cervical cancer cases worldwide.
HPV 16 is the most prevalent high-risk type and is associated with roughly 50% to 60% of cervical cancers, and it is also the primary cause of HPV-related cancers in other sites. These types are known to cause six different types of cancer, including cervical, anal, vaginal, vulvar, penile, and oropharyngeal cancers (cancers of the throat, tonsils, and base of the tongue). Persistent infection with a high-risk type is the necessary biological step for cancer to potentially develop.
The mechanism by which these viruses can drive cancer involves the expression of two viral oncoproteins known as E6 and E7. These proteins interfere with the host cell’s natural mechanisms for controlling growth and preventing tumors.
Specifically, the E6 protein targets and promotes the degradation of the tumor suppressor protein p53, which normally triggers cell death in damaged cells. Concurrently, the E7 protein binds to and inactivates the retinoblastoma protein (pRb), a protein that regulates the cell cycle.
By inactivating pRb, E7 forces the cell into a state of continuous, uncontrolled proliferation. This, combined with the failure of p53 to eliminate the damaged cell, leads to genomic instability and the gradual progression to dysplasia and eventual invasive cancer. Other high-risk types, such as HPV 31, 33, 45, 52, and 58, account for an additional 15% to 20% of cervical cancers.
Identifying Specific HPV Types
The clinical determination of which specific HPV type an individual has is generally performed as part of cancer screening or follow-up for abnormal test results. The traditional Papanicolaou (Pap) test is a key screening tool that examines collected cervical cells under a microscope to look for abnormal changes, or cytology. An abnormal Pap test often triggers further investigation.
A more direct and increasingly common approach is specific HPV DNA testing, which detects the genetic material of the virus itself. This test is primarily designed to identify the presence of the 14 high-risk HPV genotypes that pose the greatest cancer risk. Testing may be performed as an initial screening (primary HPV testing) or combined with a Pap test, a strategy known as co-testing.
For managing high-grade cervical lesions, some advanced tests also look for the expression of the viral oncoproteins E6 and E7 messenger RNA (mRNA), which is a more specific marker for a progressive, cancer-causing infection. In contrast, for benign conditions like common skin warts or genital warts caused by low-risk types, specific genotyping is usually not necessary for standard clinical care.