Cervical cancer is a sexually transmitted disease, caused by certain, specific types of the HPV virus family. Type 16 causes 50%, type 18 causes 15%, and the ten other types cause 35% of cervical cancers. Unlike women who have never had sex, sexually active women, even those who don’t have intercourse, are at risk and the risk rises with the number of intimate partners.

Luckily, most women who get infected with the HPV virus clear it spontaneously within two years. However, a small minority develops persistent infection, which can take 10 to 30 years to cause cervical cancer. Current screening recommendations are based on these two facts: a) the high spontaneous resolution rate and b) the long delay between infection and cancer. Consequently, because adolescent girls have a high rate of transient HPV infection and an extremely low rate of cervical cancer, screening should not begin before age 21. Moreover, because the risk of cervical cancer is extremely low after a negative HPV test and a negative Pap smear, re-screening need not be repeated more frequently than every five years.

In cervical cancer screening, a shift is occurring away from the traditional Pap smear towards testing for the HPV virus. Studies lasting more than ten years have shown that women who have no detectable HPV have only a 1% risk of developing cervical cancer. In contrast, women with detectible HPV have a 5% to 10% chance of developing cervical cancer. An eight-year trial in India confirmed that women who were HPV negative rarely died of cervical cancer.

Uncertain areas remain, however, because of the imperfections inherent to Pap smears and HPV tests. In a minority of cases, abnormal Pap smears may not be associated with detectable HPV, but nevertheless, may lead to cervical cancer. Also, a minority of positive HPV smears may not be associated with abnormal Pap smears, but may still lead to cervical cancer. Because of these two caveats, two strategies have evolved: a) screening with Pap smears every three years and testing for HPV only the Pap smears that reveal abnormalities, or b) co-screening with both Pap smear and HPV every five years.

Because in women ages 21 to 29, HPV prevalence is high but the risk of cervical cancer is extremely low, Pap smears only every three years are recommended. This is because testing for HPV will cause undue worry and lead to unnecessary cervical surgeries.

For women 30 to 65 years, however, co-testing with Pap smear plus HPV every five years, or else testing with Pap smears alone every three years, are the contesting strategies. When both the Pap and HPV smears are negative, the risk of cervical cancer is half that of negative Pap smears alone. Hence, among 300,000 women in the Kaiser Permanente database, of those co-tested and found to have negative Pap and HPV smears, the incidence of cervical cancer was 2/10,000 women, and the incidence of pre-cancer was 2/1000 women.

Screening is no longer recommended in women who have a low risk of cervical cancer. These include women over 65 with history of negative Pap smears, women who have had a hysterectomy for non-malignant reasons, and women who have never had sex. Heightened screening is recommended for women whose immunity is suppressed, and in those who smoke, use oral contraceptives, or have multiple births.

HPV screening alone is less expensive than co-testing with both Pap smear and HPV, and is just as good. In the study of Kaiser Permanente Northern California, the risk of cervical cancer was 0.16% after both negative Pap smears and HPV, and 0.17% after negative HPV alone. Consequently, a shift towards only HPV cervical smears every five years may soon supplant the traditional Pap smear because it is more cost effective and needs to be done less frequently.

Less than 10% of women show positive results on co-testing with both Pap and HPV smears. The commonest combination is a positive HPV and negative Pap smear, which occurs in 4% of women older than 29. Among such women, the 5-year cancer risk is 10%, which means that 90% will clear their HPV infection with time. The second commonest combination is an ambiguous Pap smear and negative HPV, which occurs in 5% of women, putting their 5-year risk of cervical cancer at about 0.05% in contrast to 0.01% for those with both, negative HPV and Pap smears. Until more data is collected, co-testing every five years with both Pap smear and HPV seems to be the preferred US strategy thus far.

Mark Schiffman, M.D., M.P.H., and Diane Solomon, M.D. Cervical-Cancer Screening with Human Papillomavirus and Cytologic Co testing. New England Journal Of Medicine 396; 24 December 12, 2013.