A significant number of Papanicolaou (Pap) smears are obtained in the United States annually, and approximately 2.5 million of them are reported to have low-grade cytologic abnormalities. Based on the Bethesda system for reporting Pap smear results, they are classified as minimally abnormal and include benign cellular changes, reactive cellular changes associated with inflammation, atypical squamous cells of undetermined significance (ASCUS), and low-grade squamous intraepithelial lesions (LSIL). Although these minimally abnormal Pap smear results are common, management strategies vary from treatment with topical or oral antibiotics to repeating the Pap smear in three to six months. Because recent data have shown a link between minimally abnormal Pap smears and bacterial vaginosis, treatment with antibiotics should, in theory, resolve the abnormality. Ferrante and colleagues studied the efficacy of 0.75 percent metronidazole vaginal gel therapy in asymptomatic patients who had minimally abnormal Pap smear results.
Study participants included women who had routine Pap smears with minimally abnormal results, defined as limited by inflammation, benign cellular changes, reactive cellular changes, or ASCUS, that did not favor any neoplastic process. Women who agreed to participate completed a questionnaire to elicit demographic information and risk factors for cervical cancer. Participants were randomized to receive treatment with 0.75 percent metronidazole vaginal gel, one applicator-full at bedtime for five days, or no treatment. Pap smears were repeated three to four months after enrollment in the study. A follow-up questionnaire was completed at that time to collect data on risk factors for abnormal Pap smears and any side effects of the antibiotic treatment.
Of the 145 women who agreed to participate in the study, 114 followed up in the appropriate time frame and were included in the data analysis. There was no difference between the control and treatment groups with regard to demographics and risk factors for abnormal Pap smears. Fifty-four percent of the follow-up Pap smears were normal. Among women whose follow-up Pap smear was normal, there was no statistical difference between those who did or did not receive treatment. Only one Pap smear worsened to LSIL during the study. The authors found no subgroups in the study for whom the treatment was effective.
The authors conclude that the use of 0.75 percent metronidazole vaginal gel to treat women with minimally abnormal Pap smears does not improve the rate of reversion to normal cytology. They conclude that metro-nidazole vaginal gel used before follow-up in women with minimally abnormal Pap smears provides no benefit and is unnecessary.
editor's note: When coping with abnormal Pap smear results, physicians face the dilemma of determining the best strategy for management. The fact that Pap smears with high-grade squamous intraepithelial lesions should be assessed by colposcopic examination of the cervix is not questioned in the literature. However, minimally abnormal Pap smear results do not have a clear-cut management strategy. The study by Ferrante and colleagues provides information about something that does not have an effect on abnormalities (i.e., empiric treatment with antibiotics). Patients with minimal abnormalities can be followed with repeat Pap smears in four to 12 months, based on their risk factors. An important comment made by the authors is that the vast majority of invasive cervical cancers occur in women who have received no screening, so we should concentrate our efforts on that population.—k.e.m.