Genital HPV: Not Necessarily for Life

ABSTRACT & COMMENTARY

Synopsis: Ho et al suggest that a more conservative approach, such as close follow-up without surgical intervention, may be appropriate for young women with newly diagnosed HPV infection or low-grade intraepithelial lesions.

Source: Ho G, et al. N Engl J Med 1998;338:423-428.

Ho and colleagues examined the prevalence of genital human papillomavirus (HPV) infection in 608 college women who were followed for up to three years with cervicolavage specimens for detection of HPV DNA by PCR and Southern Blot analysis every six months, and annual Pap smears. Twenty-six percent of the women were found to be HPV-positive at baseline. The cumulative, 36-month incidence of infection was 43%, although nearly one-half of the infections occurred within the first 12 months.

Risk factors for HPV infection included younger age, racial or ethnic minority status, increased alcohol use, and four or more sexual partners within the previous six months. Even if a woman had a single partner, her chances of acquiring cervical HPV were higher if she engaged in anal sex, frequent vaginal intercourse, or if her partner was not also enrolled in college.

The median duration of HPV infection was eight months (7-10 months, 95% C.I.). Seventy percent of infections resolved within 12 months of the incident infection, and only 9% of patients remained infected by 24 months. Persistent infection was more likely to occur in older women or in women infected with a high-risk HPV type or multiple HPV types. Squamous intraepithelial lesions were detected in 31 women, two of which were high grade. The risk of an abnormal Pap smear increased in women with prolonged HPV infections, especially those infected with high-risk types. Women with HPV infections detected at baseline were three times more likely to develop an abnormal Pap smear.

COMMENT BY CAROL A. KEMPER, MD

Cervical cancer is the second most common cancer occurring among women worldwide, although the routine use of Pap smears has substantially reduced its incidence. In addition to animal and human data demonstrating an association between certain types of HPV and cervical dysplasias and cancer, this study suggests that persistent cervical HPV infection is associated with an increased risk of squamous intraepithelial disease. While most women successfully clear their infection by age 30, persistent infection in some women, especially older women, possi- bly due to defects in cell mediated immunity, explains the peak incidence of genital cancer in women older than 40. At least 75 types of HPV are known-more than 20 of which were detected in cervicolavage samples in this study. Types 16, 18, 31, and 45 are most commonly associated with cervical cancer and are found in up to 80% of such malignancies. While the cumulative 24-month incidence of the 16 high-risk HPV types in this study was only 3%, types 16 and 18 were associated with both an increased incidence (7% and 4%, respectively) and an increased duration of infection (11 and 12 months, respectively).

Several epidemiological studies, including this one, reveal that genital HPV infections are extremely common and are acquired early in the course of a young woman's sexual life. During this three-year study, cervical HPV infection was detected at some point in almost 60% of female college students. The majority of these infections are transient, and spontaneously resolve with- in 12 months or less. Many such infections could, therefore, conceivably be missed by annual Pap smears and may never come to the attention of the clinician.

Only a relatively small proportion of women infected with HPV develop detectable cervical epithelial abnormalities, and an even smaller number develop severe dysplasia or invasive cervical cancer. Based on their findings, Ho et al suggest that a more conservative approach, such as close follow-up without surgical intervention, may be appropriate for young women with newly diagnosed HPV infection or low-grade intraepithelial lesions. (Dr. Kemper is Associate Director, AIDSProgram, Division of Infectious Diseases, Santa Clara Valley Medical Center.)