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ORIGINAL RESEARCH |
From the Division of Gynecologic Oncology, University of Arkansas for Medical Science, Little Rock, Arkansas; and the Department of Biostatistics, University of California, Los Angeles, School of Public Health, Los Angeles, California.
Address reprint requests to: Groesbeck P. Parham, MD Division of Gynecologic Oncology University of Arkansas for Medical Science 4301 Markham Street, Slot 518 Little Rock, AR 72205-7199 E-mail: parhamgroesbeckp{at}exchange.uams.edu
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Abstract |
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Methods: This was a prospective study of asymptomatic women ages 13–60 years, regularly scheduled for pelvic examinations. All women had Papanicolaou smears and magnified visual examinations with speculoscopy. Women with negative Papanicolaou smears and positive speculoscopy results were quasirandomized to immediate or deferred colposcopy groups.
Results: A total of 800 women completed all phases of the study, 124 of whom had negative Papanicolaou smears and positive speculoscopy results. Among 57 women who had immediate colposcopies, 64.9% had histologic evidence of neoplasia. Sixty-seven women had their scheduled colposcopies deferred for 6 months. During this period, 21% (14) were lost to follow-up and 29% (13) of those evaluated converted from speculoscopy positive to speculoscopy negative. Among the 32 (71%) women who remained speculoscopy positive, 90% were found to have histologic evidence of neoplasia on colposcopic biopsy.
Conclusion: In women with normal Papanicolaou smears and positive speculoscopy results, the diagnostic yield can be improved by deferring colposcopy for 6 months. Deferral should be considered only for women who are reliable for follow-up.
Previous studies have demonstrated that speculoscopy, a visual evaluation of the cervix using a blue-white chemiluminescent light source, Speculite (The Trylon Corporation, Torrance, CA), significantly increased detection rates of underlying low-grade and high-grade cervical neoplasias when combined with the Papanicolaou smear as Pap Plus Speculoscopy (The Trylon Corporation).1–3 However, like other adjunctive visual tests, such as Cervicography and colposcopy, speculoscopy predictably results in an increase in false-positive identifications compared with Papanicolaou smear alone.4–6 The identification of abnormal tests in women who have no underlying cervical neoplasia has been cited as a potential source of needless anxiety and expense. This potential cost has to be balanced against the benefit of a significant increase in sensitivity with the addition of the visual adjunct.
One of the questions frequently raised regarding the Pap Plus Speculoscopy screening protocol is how to manage the subgroup of women with normal Papanicolaou smears and positive speculoscopy results. Previous studies have shown that 45–65% of these women have underlying cervical abnormalities.1–3 It has been suggested that high-risk women should have immediate colposcopy and low-risk women should be rescheduled for a repeat Pap Plus Speculoscopy in 6–12 months.1 It has been postulated that this interval would allow the spontaneous resolution of some low-grade cervical lesions.7,8 The current study evaluated the effect of such a delay in this subgroup of women.
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Methods |
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After admission to the study, the women had Papanicolaou smears done routinely using an Ayres spatula and endocervical cytobrush to prepare single slide specimens. An illuminated blue-white Speculite (The Trylon Corporation) was attached to the speculum before insertion. The cervix and vaginal vault were irrigated with 5% acetic acid. After 1 minute, the room lights were extinguished and the cervix was viewed with a hand-held optic providing 4–6x magnification (Perisphere Industries, Torrance, CA). Examinations were done by nurse practitioners and residents trained in speculoscopy by viewing a training video. The results of the speculoscopy examinations were recorded on a data sheet that became part of the patient’s record. As described previously,1–3 a speculoscopy examination was considered positive if an acetowhite area with at least one distinct border was seen. Speculoscopy was considered negative if no distinct acetowhite areas were seen. In women with positive speculoscopy results, a sample was collected for human papillomavirus (HPV) DNA testing using the hybrid capture technique (Digene Diagnostics, Silver Spring, MD).
Papanicolaou smears were interpreted using the Bethesda system of classification9 and were read at the University of Arkansas for Medical Science Medical Center, Department of Pathology, or at LabCorp of America (State Health Department patients). In each laboratory, the same guidelines were used for slide interpretation, and the two laboratories had similar rates for positive Papanicolaou smears and for atypical squamous cells of undetermined significance (ASCUS). A positive Papanicolaou smear was defined as low-grade squamous intraepithelial lesions (SIL) or worse for the purposes of Pap Plus Speculoscopy test result classification. Women with Papanicolaou smears read as ASCUS were considered separately because such women are typically managed by specific protocols. The positive or negative speculoscopy results for women with Papanicolaou smears read as ASCUS were reported so that the contribution of speculoscopy to each group could be evaluated. There was no secondary interpretation of slides determined to be positive or to have ASCUS.
Negative Papanicolaou smears from the State Health Department were sent for re-evaluation by computerized quality control using the PapNet system (Neuro-medical Systems, Suffern, NY). Negative Papanicolaou smears from the University of Arkansas were subjected to an internal 20% review. Any changes in Papanicolaou smear interpretation resulting from this quality-assurance review were considered the final Papanicolaou smear results for data analysis.
For classifying Pap Plus Speculoscopy results, six different categories were defined (Table 1
). Women with positive Papanicolaou smears or smears with ASCUS were scheduled for immediate colposcopy and biopsy. Women with negative Papanicolaou smears and positive speculoscopy results were assigned in a quasirandom fashion to two groups, one scheduled for colposcopy within 4 weeks and the other with colposcopy deferred for 6 months (the desired follow-up period). Group assignment was done at enrollment using the women’s social security numbers (odd or even) as the determinant. Women in the deferred group had a repeat Pap Plus Speculoscopy examination at the time of deferred colposcopy. Any changes in their initial and repeat Pap Plus Speculoscopy results were compared. Colposcopy was done by an experienced colposcopist (more than 5 years of experience), and if any abnormalities were seen, punch biopsies were performed. If the colposcopy was inadequate, an endocervical curettage was performed.
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2 analysis and Fisher exact test. Where appropriate, data were analyzed with the McNemar adaptation of the 2 test. Quantitative data were compared using Student t test. |
Results |
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, along with the results of the colposcopies.
A total of 124 women had negative Papanicolaou smears and positive speculoscopy results and were assigned to immediate or deferred colposcopy. Table 2 shows that there were no significant differences in age, percentage of positive colposcopies, and overall prevalence of disease between these groups, making them appropriate for comparison from an epidemiologic perspective. Whereas all 57 women in the immediate-colposcopy group underwent colposcopy, only 45 of the 67 women in the deferred group returned for a repeat Pap Plus Speculoscopy examination and colposcopy. The mean follow-up period for these 45 women was 6.75 ± 1.0 months, with a median follow-up of 6 months. Only two women were followed up more than 8 months later.
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shows that 32 of the 45 women (71%) in the deferred colposcopy group continued to have positive speculoscopy results. In two of these 32 women the Papanicolaou smear was positive, in four the smear showed ASCUS, and 26 of 32 still had negative Papanicolaou smears. In 13 women, repeat speculoscopy results became negative; the Papanicolaou smear remained negative in 12 and was read as ASCUS in one.
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Of the 22 women in the deferred-colposcopy group who did not follow up at one of the study centers, information was available that seven women had followed up with other clinics or physicians (data not available), and one woman had undergone hysterectomy. The remaining 14 women were considered lost to follow-up after they failed to respond to three attempts at contact. Table 4 presents a univariate comparison of multiple demographic factors between this group of 14 women and the 32 women who did have follow-up.
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Discussion |
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show that nearly two-thirds of the women with negative Papanicolaou smears and positive speculoscopy results in this study had underlying cervical neoplasia that would have gone undetected without the addition of speculoscopy. In the deferred-colposcopy arm, for women who initially had normal Papanicolaou smears but positive speculoscopy results, repeat smears using low-grade SIL or ASCUS as the criterion for positivity were still insensitive for detecting cervical neoplasia. In contrast, the presence or absence of visual abnormalities on speculoscopy in these women correlated closely with biopsy-confirmed neoplasia.
Although speculoscopy and other in vivo screening adjuncts improve the sensitivity of screening for cervical pathology,2,3,12–15 one of the concerns raised with these tests is the possibility that the increase in sensitivity will be accompanied by a significant increase in false-positive results, which could impair the cost-effectiveness of adding a second test to the Papanicolaou smear. In the current study, we investigated the benefits of delaying colposcopy in Papanicolaou-negative, speculoscopy-positive women for approximately 6 months, allowing for spontaneous regression of low-grade lesions. After 6 months, 29% (13 of 45) of these women’s speculoscopy results converted from positive to negative (Table 3). Biopsy data showed that the prevalence of neoplasia in this converted subgroup of women was small (2 of 13, 15%) and of a low-grade nature.
In contrast to these 13 women, 32 women (71%) in the deferred group still had positive speculoscopy results on repeat examinations. Comparing the data from this group with the data from those women whose speculoscopy results reverted to normal (Tables 2 and 3), it is clear that waiting 6 months before performing colposcopy in Papanicolaou-negative, speculoscopy-positive women significantly increases the yield from colposcopy. By waiting 6 months, 13 women with initially positive Pap Plus Speculoscopy tests converted to negative results and, in clinical practice, would not require colposcopy. In those with persistently positive Pap Plus Speculoscopy results, colposcopy would have a yield of neoplasia in excess of 90%.
As described earlier, 14 of the 67 women (21%) in the deferred-colposcopy group were lost to follow-up. Univariate comparison of the factors listed in Table 4 using a two-sample t test or Fisher exact test showed that only cigarette smoking history was significantly different between the groups. A logistic regression analysis16 confirmed that only smoking history was significantly different between the groups (P < .015). This analysis indicated that in the high-risk clinic population at the State Health Department, there did not appear to be any identifiable patient-related factors that would allow a clinician to accurately predict compliance with eventual follow-up for repeat Pap Plus Speculoscopy.
The data from this study indicated that from the standpoint of improving the use of colposcopy services, there was an advantage in delaying colposcopy in women with normal Papanicolaou smears and positive speculoscopy results. This advantage was manifested by the conversion of both positive speculoscopy results and cervical neoplasia in nearly 30% of the women with initial Papanicolaou-negative, speculoscopy-positive screening results in the deferred arm of this study. These data are similar to data reported in studies that evaluated delaying colposcopy in women with Papanicolaou smears showing ASCUS or minimally abnormal cells17–21 and are consistent with the theory that a proportion of low-grade SIL will regress spontaneously.
Although the data from the current study showed that delaying colposcopy in Papanicolaou-negative, speculoscopy-positive women can increase the diagnostic yield from women with persistently positive speculoscopy, it must be kept in mind that these data are from a single series of 800 high-risk patients and may not be directly applicable to other populations. It is also important to recognize that although there was an improvement in the diagnostic yield from colposcopy associated with a delay in this procedure, there is a risk that some women will not return for their repeat Pap Plus Speculoscopy examinations. In the current investigation, just over 20% of the women in the deferred-colposcopy arm were lost to follow-up. Although this degree of patient loss is applicable only to this limited population of high-risk women, the data presented in Table 4 indicate that demographics and history do not help in selecting women who are appropriate for referral. Thus, it appears that only practices with high retention rates should consider deferring colposcopy in women with normal Papanicolaou smears and positive speculoscopy results. In these practice scenarios, the data from this study indicate a possible improvement in the diagnostic yield of colposcopy and a more cost-effective use of resources. Further data from practice situations in which this triage is in place will help clarify how much improvement will be realized.
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Footnotes |
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Received April 14, 1999. Received in revised form July 16, 1999. Accepted August 5, 1999.
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References |
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