CERVICAL DISEASE

Which test should be used first?

Basic screening principles suggest that, whenever 2 tests are used in combination, the most sensitive test should be used first, with patients who test positive tested again using the second, more specific, test. These principles suggest we should be using HPV testing alone as the initial screening test and limiting the use of cytology to triage HPV-positive women. This sequence of testing could potentially be done in a “reflex” fashion.

The large Italian screening trial by Ronco and colleagues randomized 33,364 women aged 35 to 60 years to 2 different screening strategies: routine conventional cytology or liquid-based cytology with HPV testing.³ In the routine cytology arm, researchers identified only 51 cases of CIN 2,3 or cancer, but in the experimental arm, they identified 75 cases. A breakdown of the initial screening results in the women found to have CIN 2,3 or cancer in the experimental arm shows that cytology adds very little benefit. Only 2 of 75 women with CIN 2,3 or cancer were identified by cytology alone. In contrast, 21 (28%) of the cases of CIN 2,3 or cancer were in women who were high-risk HPV-positive and cytology-negative (TABLE 2).

TABLE 2

How cytology and HPV testing compare: Results from the Italian screening trial

The United States is falling behind other countries in assessing how best to utilize HPV testing for screening. Ongoing trials in The Netherlands, Italy, United Kingdom, Canada, and Finland are evaluating whether cytology can be replaced by HPV DNA testing for screening. Currently, HPV testing is only approved as an adjunct to cytology for cervical cancer screening in the United States, and no similar trials are under way.

OCs not linked to HPV infection, and condoms afford some protection

Vaccarella S, Lazcano-Ponce E, Castro-Garduno JA, et al. Prevalence and determinants of human papillomavirus infection in men attending vasectomy clinics in Mexico. Int J Cancer. 2006;119:1934–1939.

Vaccarella S, Franceschi S, Herrero R, et al. Sexual behavior, condom use, and human papillomavirus: pooled analysis of the IARC human papillomavirus prevalence surveys. Cancer Epidemiol Biomarkers Prev. 2006;15:326–333.

Winer RL, Hughes JP, Feng Q, et al. Condom use and the risk of genital human papillomavirus infection in young women. N Engl J Med. 2006;354:2645–2654.

No question: Anogenital HPV infections are transmitted almost exclusively through intimate sexual contact.³ The standard markers of sexual exposure, such as the number of sexual partners and the number of partners that one’s partner has had, are key risk factors for infection with HPV. Women often ask whether other factors such as oral contraceptive (OC) use, diet, smoking, and condom use affect their risk for infection. But nonsexual risk factors are difficult to evaluate because the strength of sexual risk factors is so high.

To clarify the role played by non-sexual factors, the International Association for Research on Cancer (IARC) pooled data from multiple HPV prevalence studies involving more than 15,000 women from 14 different areas worldwide. This study clearly indicates that the use of OCs is not associated with HPV infection. Current, former, and never users of OCs all had the same risk of being HPV-positive. Therefore, although OCs are a risk factor for cervical cancer, the elevated risk cannot be explained by an increased susceptibility to HPV infection. This study also found that the menopausal transition had no clear effect on HPV infection.

New data show condoms to be more beneficial than not

Condoms are widely recognized as an effective barrier to the sexual transmission of HIV; their efficacy in blocking the transmission of other sexual diseases is less well documented. Most studies that have evaluated the impact of condom use on HPV infection have failed to find a beneficial effect. This may reflect the fact that condoms are often used inconsistently. In addition, there is a tendency to use condoms when having higher-risk sexual encounters, such as with a new partner.

In a recent study from Seattle, Winer and colleagues followed 82 female university students who first initiated sex while enrolled in the study or within 2 weeks of joining the study. The incidence of HPV infection was 38 per 100 patient-years of follow-up among women whose partners used condoms during all acts of intercourse, compared with 89.3 per 100 patient-years of follow-up among women whose partners used condoms less than 5% of the time. Risk reductions were observed for both high- and low-risk types of HPV.

Condoms also appeared to protect against the development of CIN. There were no cases of CIN during 32 patient-years among women whose partners consistently used condoms, compared with 14 cases of incident CIN during 97 patient-years of follow-up among women whose partners did not use condoms or who used them less consistently.