Facts summarized on the Human Papilloma Virus (HPV) from Report of an External Consultants’ Meeting. Department of Health and Human Services, Atlanta: Centers for Disease Control and Prevention (CDC), December 1999.

• Approximately 30 types cause infection of genital mucosal sites, and these genital types are generally characterized as “high-risk” types (e.g., HPV 16, 18, 31, 33, 35, 39, 45, 51, 52), which are associated with low- and high-grade squamous intraepithelial lesions (LSIL and HSIL) and invasive cancer, and “low-risk” types (e.g., HPV 6, 11, 42, 43, 44), which are primarily associated with genital warts, LSIL, and re-current respiratory papillomatosis (RRP).
  
  
• A recent assessment of the magnitude of various STD in the U.S. estimated an annual incidence of genital HPV infection of 5.5 million and a prevalence of current infection (detectable HPV DNA) of 20 million. The majority of infections with all types appear to be subclinical, detectable neither by physical exam nor cytology, but only by the use of HPV DNA detection tests.
  
  
• Among sexually active women, over 50% have been infected with one or more genital HPV types, approximately 15% have evidence of current infection, 50-75% of which is with high-risk types, and 1% have genital warts.
  Although smoking, pregnancy, and use of oral contraceptives have been variably associated with genital HPV infection, the most consistent predictor Factor is the # of sexual partners.
  
  
• Over the last 15 years, however, the central role of HPV in the pathogenesis of cervical cancer has been firmly established. High-risk types of HPV are found in > 93% of cervical cancers worldwide, with HPV 16 present in 50% and HPV 18, 31, and 45 in another 30%.
• In the U.S., incidence rates for cervical cancer are currently 8.3/100,000, with approximately 14,000 cases and 5000 deaths annually.
  
  
• An estimated 2.5 million Pap smears with low-grade abnormalities (e.g., atypical squamous cells of undetermined significance–ASCUS, atypical glandular cells of undetermined significance–AGUS, and LSIL) and 200,000-300,000 Pap smears with HSIL are detected annually in the U.S.
  
  
• Estimates for genital warts incidence rates in the U.S. may be as high as 100 per 100,000 with a prevalence of 1.4 million.
  
  
• Estimates for RRP, a disease of both children and adults in which papillomas of the larynx and upper respiratory tract cause hoarseness and respiratory obstruction, are similarly imprecise, with estimated incidence rates of 0.4 to 1.2 per 100,000 children. the likely mode of transmission for RRP is upper respiratory tract exposure to infected genital mucosa, at the time of delivery in juvenile-onset disease and presumably through oral-genital sexual contact for adults.
  
  
• Median duration of HPV incident genital infection is reported to be 8 months, with rates of persistence of only 30% after 1 year and 9% after 2 years.
  
  
• An increasing body of data suggests that the majority of type-specific genital HPV infections are only transiently detectable by DNA detection techniques. Most studies have noted an inverse relationship of age with infection as measured by detection of HPV DNA. Peak rates are found in women < 25 years old, which is speculated to result from clearance of infection over time in most women as an effective immunologic response is induced.
  
  
• Women with persistent infection, especially those with high-risk types, are at greater risk for developing CIN.
  
  
• HPV testing for triage of low-grade Pap smear abnormalities (e.g., ASCUS, AGUS, and LSIL) : Although the majority of women with these cytologic findings have normal histology or lesions which are likely to regress (CIN 1), a minority (5-20%) will have CIN 2/3. The largest evaluation to date of HPV testing for triage, demonstrate high sensitivity (approximately 90%) and acceptable specificity (40-65%) for detection of CIN2/3 for women with ASCUS; similar results have been found in women with AGUS. Test specificity and positive predictive value for detecting CIN2/3 are lower in settings where the prevalence of HPV infection is higher, such as younger women or those with LSIL.
  
  
• The use of HPV testing to manage women with confirmed CIN, interest stems from natural history studies which indicate that persistent high-risk HPV infection predicts subsequent development of CIN 2/3, and from studies of women with treated CIN which indicate that persistent HPV is associated with recurrent CIN.
  
  
• Because the large majority of CIN 1 lesions regress without treatment, their routine treatment is not recommended, although close follow-up is required when treatment is deferred. Determination of whether high-risk HPV types are present, and if so, whether they persist, may help select a group in whom closer follow-up and/or treatment may be most useful. Likewise, following ablative treatment of CIN, approximately 10-15% of women will experience a recurrence. Presence of high-risk types of HPV DNA is associated with recurrences, and follow-up HPV testing could enhance identification of those most likely to recur, allowing more intensive follow-up.
  
  
• Modeling studies suggest that CIN has a higher probability of regression in younger than older women, which is likely a result of higher rates of recently acquired genital HPV infection in young women, whose manifestations are usually transient, in contrast to the greater likelihood of persistent infection in older women.
  
  
• Because the large majority of cervical lesions in adolescents are self-limited, in those with low-grade cytologic abnormalities (e.g., ASCUS, LSIL) consideration should be given to conservative follow-up by repeat Pap smear rather than triage by HPV testing (since predictive value in adolescents is not well-characterized) or by early colposcopy/biopsy.
  
  
• Studies which have attempted to assess male condom benefit for women have generally found no evidence of protection against infection. There are data suggesting a benefit of condom use for men, although the studies are limited, and no data is available for female condoms for either women or men.
  
  
• t has been speculated that treatment of genital warts might be useful in reducing infectiousness. This premise is difficult to test because of the lack of assays for infectivity, but is supported by observations that treatment of genital warts with the imunomodulating agent imiquimod reduces viral DNA and mRNA in post-treatment biopsies and that therapy of CIN results in clearance of HPV in follow-up cervical swabs in 70-80% of women. However, clinically normal skin and mucosa in the vicinity of HPV-associated lesions often contain HPV. This reservoir is thought to explain the typical recurrence rates of 10-20% after treatment for CIN, and 20-50% after treatment of genital warts and the fact that treatment of partners does not influence recurrence rates of genital warts.
  
  
• Thus, based on limited existing data, currently available therapies for HPV-related lesions may reduce but probably do not eliminate infectiousness, and whether the reduction in viral load which occurs with treatment impacts future transmission remains unclear.
  
  
• Because duration of infectiousness is unknown and because genital HPV is so common among persons who have been sexually active, the value of disclosing a past diagnosis of HPV infection to future sex partners is unclear, although candid discussions about past STD should be attempted whenever possible.
  
  
• Anal cancer is a relatively uncommon malignancy, with a current U.S. incidence rate of only 0.9/100,000. However, incidence rates are reported to have increased over the past 20-30 years in several countries, including the U.S., where rates increased by 96% for men and 39% for women from 1973-97. This increase has been partly ascribed to changes in sexual activity. There is a growing body of data linking anal cancer to sexual behavior, especially anal intercourse, and HPV infection.
  
  
• Women with previous cervical cancer are also at higher risk for anal cancer, an association likely attributable to the presence of HPV infection at both sites.
  
  
• These data have lead to consideration of the potential benefit of anal cancer prevention programs through cytologic screening, since evaluations to date suggest that anal Pap smears may be similar in sensitivity to cervical smears.