Applied Evidence

Natural History of HPV Infections

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Transmission of HPV

Most papillomavirus infections are transmitted through close skin-to-skin or mucosa-to-mucosa contact. Epidemiologic studies clearly indicate that sexual intercourse is the primary route for anogenital HPV infection.1 Infection is relatively uncommon in women who have not had intercourse, and there is a strong and consistent relationship between the number of both lifetime and recent sexual partners and the prevalence of HPV in women. There is also a strong association between having had a recent new sexual partner(s) and incident anogenital HPV infection. Consistent condom use reduces—but does not eliminate—HPV transmission.2 In a prospective study on college students who initiated sexual intercourse either after or immediately prior to enrollment, the overall rate of anogenital HPV infection was 89 per 100 patient-years of follow-up in those whose partners rarely used condoms during sexual intercourse, compared with 38 per 100 patient-years of follow-up among those whose partners always used condoms.

Penetrative sexual intercourse is not a requirement for HPV transmission. Both oral and digital HPV infections occur, and there is evidence that digital-genital and oral-genital contact can result in the transmission of HPV, albeit at relatively low rates. In a study of college students from Seattle, the 2-year cumulative incidence of HPV infections was 38.8% in those who were sexually active at enrollment.3 Among college students who remained virginal, the 2-year cumulative incidence of HPV was 9.7% in those who reported nonpenetrative sexual contact, but only 1.3% in those who reported no sexual contact whatsoever. HPV also can be transmitted perinatally.1

Although the clinical significance of HPV perinatal transmission is unknown, this route of transmission is well documented. A recent study of oral and genital HPV infections in infants born to both HPV-positive and HPV-negative women detected HPV DNA in 6% of the infants at birth, 13% at 6 weeks after birth, and 9% between 3 to 24 months of age.4 Approximately half of the HPV infections in infants were oral and half were genital. Interestingly, persistence of HPV infection was uncommon in the newborns—only 1.4% had the same HPV type detected on 2 or more occasions. Therefore, most of these infections appear to be very transient, and it is unlikely that the majority have adverse clinical consequences.

Initial HPV infections and prevalence of HPV in the population

Most sexually active adolescents and women become infected with HPV within several years of initiating sexual activity. A prospective follow-up study of sexually naïve college students found that within 12 months of initiating sexual intercourse, 30% became HPV positive; within 48 months, 54% were HPV positive.3 Other follow-up studies of adolescents and young women have found that with repeated testing and long-term follow-up, HPV is detected in more than two-thirds over a several-year period.5-7

Women with transient HPV infections often develop cytological abnormalities while they are actively shedding HPV DNA. This occurs because productive HPV infections result in cytological abnormalities in the infected epithelial cells. Cells with these cytological features are found in about one-third of HPV-infected women and result in a diagnosis of either low-grade squamous intraepithelial lesions (LSIL) or atypical squamous cells of undetermined significance (ASC-US).8 If followed, cytological abnormalities continue to be detected for approximately 1 to 2 years, but by 4 years, the risk of having an abnormal cervical cytology is similar to that of women in the general population.9

The majority of HPV infections are self-limited and spontaneously clear within a several-year period as a result of cell-mediated immunity. In one study, two-thirds of adolescents infected with low-risk HPV types spontaneously cleared their infections by 12 months, as did over half of those infected with high-risk HPV types ( FIGURE 1 ).5 By 23 months, more than 80% had cleared their HPV infections. In another follow-up study of adolescents and young women with LSIL, 91% of HPV-infected individuals cleared their infections after 36 months of follow-up.10 However, many women who spontaneously clear one specific type of HPV become infected with another HPV type. This is part of the reason that infection with multiple types of HPV is quite common in sexually active adolescents and young women.

The natural history of HPV infections explains the prevalence of HPV infection in women in the general population. Since infection is sexually transmitted and is usually transient, the prevalence of HPV infections is highest among sexually active women in their 20s. With increasing age, women tend to have fewer new sexual partners, and prevalence decreases. After age 45, the prevalence of high-risk HPV infections tends to stabilize, and less than 5% of women in the general population are DNA positive for high-risk types of HPV. The prevalence of HPV DNA positivity drops to less than 3% of women with a normal cervical cytology result.11


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