Most HPV infections are asymptomatic and result in no clinical disease. Clinical manifestations of HPV infection include anogenital warts, recurrent respiratory papillomatosis, cervical cancer precursors (cervical intraepithelial neoplasia), and cancers, including cervical, anal, vaginal, vulvar, penile, and some head and neck cancer.
Human papillomaviruses are small, double-stranded DNA viruses that infect the epithelium. More than 100 HPV types have been identified; they are differentiated by the genetic sequence of the outer capsid protein L1. Most HPV types infect the cutaneous epithelium and cause common skin warts. About 40 types infect the mucosal epithelium; these are categorized according to their epidemiologic association with cervical cancer. Infection with low-risk, or nononcogenic types, such as types 6 and 11, can cause benign or low-grade cervical cell abnormalities, genital warts and laryngeal papillomas. High-risk, or oncogenic, HPV types act as carcinogens in the development of cervical cancer and other anogenital cancers. High-risk types (currently including types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 69, 73, 82) can cause low-grade cervical cell abnormalities, high-grade cervical cell abnormalities that are precursors to cancer, and anogenital cancers. High-risk HPV types are detected in 99% of cervical cancers. Type 16 is the cause of approximately 50% of cervical cancers worldwide, and types 16 and 18 together account for about 70% of cervical cancers. Infection with a high-risk HPV type is considered necessary for the development of cervical cancer, but by itself it is not sufficient to cause cancer because the vast majority of women with HPV infection do not develop cancer.
In addition to cervical cancer, HPV infection is also associated with anogenital cancers less common than cervical cancer, such as cancer of the vulva, vagina, penis and anus. The association of genital types of HPV with non-genital cancers is less well established, but studies support a role for these HPV types in a subset of oral cavity and pharyngeal cancers.
HPV has not been isolated in culture. Infection is identified by detection of HPV DNA from clinical samples. Assays for HPV detection differ considerably in their sensitivity and type specificity, and detection is also affected by the anatomic region sampled as well as the method of specimen collection.
Currently, only the Digene Hybrid Capture 2® (hc2) High-Risk HPV DNA Test is approved by the Food and Drug Administration for clinical use The hc2 uses liquid nucleic acid hybridization and detects 13 high-risk types (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68). Results are reported as positive or negative and are not type-specific. The hc2 test is approved for triage of women with equivocal Papanicolaou (Pap) test results (ASC-US, atypical cells of undetermined significance) and in combination with the Pap test for cervical cancer screening in women 30 years of age and older. The test is not clinically indicated nor approved for use in men.
Epidemiologic and basic research studies of HPV generally use nucleic acid amplification methods that generate type-specific results. The PCR assays used most commonly in epidemiologic studies target genetically conserved regions in the L1 gene.
The most frequently used HPV serologic assays are VLP-based enzyme immunoassays. However, laboratory reagents used for these assays are not standardized and there are no standards for setting a threshold for a positive result.
HPV is transmitted by direct contact, usually sexual, with an infected person. Transmission occurs most frequently with sexual intercourse but can occur following nonpenetrative sexual activity.
Studies of newly acquired HPV infection demonstrate that infection occurs soon after onset of sexual activity. In a prospective study of college women, the cumulative incidence of infection was 40% by 24 months after first sexual intercourse. HPV 16 accounted for 10.4% of infections.
Genital HPV infection also may be transmitted by nonsexual routes, but this appears to be uncommon. Nonsexual routes of genital HPV transmission include transmission from a woman to a newborn infant at the time of birth.
HPV infection occurs throughout the world.
HPV is presumably communicable during the acute infection and during persistent infection. This issue is difficult to study because of the inability to culture the virus. Communicability can presumed to be high because of the large number of new infections estimated to occur each year.
Viruses in the papillomavirus family affect other species (notably rabbits and cows). However, humans are the only natural reservoir of HPV.
Risk factors for HPV infection are related to sexual behavior, including the number of sex partners, lifetime history of sex partners, and the partners’ sexual history. Most studies suggest that young age (less than 25 years) is a risk factor for infection. Results of epidemiologic studies are less consistent for other risk factors, including young age at sexual initiation, inconsistent condom use, number of pregnancies, genetic factors, smoking, lack of circumcision of male partner, and oral contraceptive use.
There is no known seasonal variation in HPV infection.
HPV transmission can be reduced but not eliminated with the use of physical barriers such as condoms. Recent studies demonstrated a significant reduction in HPV infection among young women after initiation of sexual activity when their partners used condoms consistently and correctly. Abstaining from sexual activity (i.e., refraining from any genital contact with another individual) is the surest way to prevent genital HPV infection. For those who choose to be sexually active, a monogamous relationship with an uninfected partner is the strategy most likely to prevent future genital HPV infections.
Most cases and deaths from cervical cancer can be prevented through detection of precancerous changes within the cervix by cervical cytology using the Pap test. Currently available Pap test screening can be done by a conventional Pap or a liquid-based cytology. CDC does not issue recommendations for cervical cancer screening, but various professional groups have published recommendations. The American College of Obstetricians and Gynecologists (ACOG), the American Cancer Society (ACS), and the U.S. Preventive Services Task Force (USPSTF) guidelines recommend that all women should have a Pap test for cervical cancer screening within 3 years of beginning sexual activity or by age 21, whichever occurs first. While the USPSTF recommends a conventional Pap test at least every 3 years regardless of age, ACS and ACOG recommend annual or biennial screening of women younger than age 30, depending on use of conventional or liquid–based cytology. According to these national organizations, women over age 30 with three normal consecutive Pap tests should be screened every 2 to 3 years.
The use of HPV vaccine does not eliminate the need for continued Pap test screening, since 30% of cervical cancers are caused by HPV types not included in the vaccine.
Souce: Human Papillomavirus
Epidemiology and Prevention of Vaccine-Preventable Diseases
The Pink Book: Course Textbook - 12th Edition Second Printing (May 2012)
For more information about Human Papillomavirus vaccines, please see the following sections from the Human Papillomavirus chapter of The Pink Book, 12th Edition