The Pap Test
The Pap test has never been examined in a randomized controlled trial. A large body of consistent observational data, however, supports its effectiveness in reducing mortality from cervical cancer. Both incidence and mortality from cervical cancer have sharply decreased in a number of large populations following the introduction of well-run screening programs.[16,17,18,19] In Iceland, the mortality rate declined by 80% for more than 20 years, and in Finland and Sweden by 50% and 34%, respectively.[16,20] Similar reductions have been observed in large populations in the United States and Canada. Reductions in cervical cancer incidence and mortality were proportional to the intensity of screening.[16,20] Mortality in the Canadian provinces was reduced most remarkably in British Columbia, which had screening rates two to five times those of the other provinces.
Case-control studies have found that the risk of developing invasive cervical cancer is three to ten times greater in women who have not been screened.[22,23,24,25] Risk also increases with long duration following the last normal Pap test, or similarly, with decreasing frequency of screening.[26,27] Screening every 2 to 3 years, however, has not been found to increase significantly the risk of finding invasive cervical cancer above the risk expected with annual screening.[27,28]
Alternative Screening and Treatment Strategies in Low-resource Settings
Choice in methods of screening for cervical cancer in resource-limited countries or underserved populations has prompted the evaluation of one-time screen-and-treat approaches for cervical cancer screening.
A clustered randomized, controlled trial in rural India evaluated the impact of one-time visual inspection of the cervix with acetic acid (VIA) and immediate colposcopy, directed biopsy, and cryotherapy (where indicated) on cervical cancer incidence and mortality in healthy women aged 30 to 59 years. Fifty-seven clusters (n = 31,343 women) received the intervention, while 56 control clusters (n = 30,958 women) received counseling and education about cervical cancer screening. After 7 years of follow-up, with adjustments for age, education, marital status, parity, and cluster design, there was a 25% relative reduction in cervical cancer incidence in the intervention arm compared with the control group (hazard ratio [HR] = 0.75; 95% confidence interval [CI], 0.55-0.95). Using the same adjustments, cervical cancer mortality rates demonstrated a 35% relative reduction in the intervention arm compared with the control group (HR = 0.65; 95% CI, 0.47-0.89); the age-standardized rate of death due to cervical cancer was 39.6 per 100,000 person-years for the intervention group versus 56.7 per 100,000 person-years for the control group. However, the same authors have subsequently reported that HPV testing is superior at reducing cervical cancer mortality using the same cohort. This population was essentially screen naive at entry into the study and demonstrated a much higher overall risk for cervical cancer death (11% of the controls) than that observed in the U.S. population; the applicability of these findings to the United States and similar western health care systems is therefore difficult to assess. Histological diagnosis of cervical lesions happened after treatment had already taken place, and approximately 27% of patients in this trial received cryotherapy for lesions later determined to be nonmalignant.