Hypothesis: the act of taking a Papanicolaou smear reduces the prevalence of human papillomavirus infection: a potential impact on the risk of cervical cancer

Abstract

Background: Based on data collected in a case–control study of hormonal contraceptive use and invasive cervical cancer among South African colored and black women, we have reported a five-fold reduction in incidence among women who in their lifetimes had previously received as few as two Papanicolaou (Pap) smears. Given the conditions prevailing in the community under study, a reduction in risk of this magnitude was surprising. We hypothesized that the act of performing a Pap smear may trigger an immune response to human papillomavirus (HPV) infection and thus reduce the risk of cervical cancer. Methods: Among 1540 control women we compared prevalence rates of infection with specific HPVs known to cause cervical cancer among those who previously received 0, 1, 2 or ≥3 Pap smears in their lifetimes. Findings: Overall, 16% of the controls were HPV-positive. Among women who received 0, 1, 2 and ≥3 Pap smears the HPV positivity rates were 24, 17, 12, and 11%, respectively. Compared with never having received a smear, the confounder-adjusted relative risk estimates for the receipt of 1, 2, and ≥3 smears were 0.7 (95% confidence interval, 0.5–1.0), 0.5 (0.3–0.8), and 0.5 (0.3–0.7), respectively (test for trend among Pap smear recipients: p = 0.04). The data were consistent within strata of age, parity, and race. Interpretation: The data are compatible with the hypothesis that the minor trauma involved in taking a Pap smear may reduce the risk of cervical cancer by triggering an immune response to HPV infection.