CHLAMYDIA TRACHOMATIS (CT) and Neisseria gonorrhoeae (GC) are the most common sexually transmitted bacteria reported in young men and women, causing infections of the epithelial cells lining the cervix and/or urethra. These organisms often infect the lower genital tract without symptoms, enabling them to go undetected and untreated. This asymptomatic presence may result in ascending infections, especially in women, resulting in upper genital tract complications1 with high morbidity and substantial costs.2C. trachomatis infection has been shown to increase the risk of human immunodeficiency virus acquisition3 and also may be a risk factor for the development of cervical cancer.4 Prevention of pelvic inflammatory disease, ectopic pregnancy, and tubal factor infertility resulting from CT or GC will require screening programs of sexually active young men and women.
Nucleic acid amplification (NAA) assays such as transcription meditated amplification (TMA), strand displacement amplification (SDA), polymerase chain reaction (PCR), and ligase chain reaction (LCR) are sensitive and specific methods for testing traditional samples from the lower genital tract such as cervical and urethral swabs.5 Recognition that asymptomatic patients will need to be screened to control CT and GC has led to an interest in evaluating the performance of the NAA tests on noninvasive specimens such as first-catch urine (FCU), vulva, introital, and vaginal swabs.6–14 Collectively, these studies have shown that urine testing detects an equal number or slightly fewer infections compared with traditional sampling. A few studies have addressed the comfort and preference of self-collecting noninvasive samples for diagnosing sexually transmitted infections (STIs).15–18 Because patient-collected vaginal swabs could serve as screening samples in populations that are at risk and difficult to reach, we embarked on a multicentered study to determine the ease and preference of them compared with urine, clinician-collected cervical swabs, and vaginal swabs after these women participated in a larger study that compared the ability of Gen-Probe Incorporated’s APTIMA COMBO 2 Assay (AC2), APTIMA CT Assay for CT, and the APTIMA GC Assay for GC to detect C. trachomatis and N. gonorrhoeae in various samples.
Subjects and Study Sites
A total of 1509 women were enrolled in a diagnostic study from clinics for family planning, sexually transmitted diseases (STDs), teenagers, and student health from 8 North American centers, including Hamilton (HAM), Ontario; Jacksonville (JAX), Florida; New Orleans (NOR), Louisiana; Pittsburgh (PIT), Pennsylvania; Houston (HOU), Texas; Chicago (CHI), Illinois; Birmingham (BIR), Alabama; and San Francisco (SAN), California. Subjects were classified as symptomatic if they reported symptoms such as discharge, dysuria, and pelvic pain. Asymptomatic status was assigned to those patients who did not report symptoms regardless of any signs detected by the clinician during examination. A total of 45 patients were withdrawn from the study because they had taken antibiotics within 21 days (n = 2), urinated within 1 hour previous to providing an FCU specimen or did not provide the required number of specimens (n = 11), erroneously enrolled twice (n = 11), decided to withdraw from the study (n = 4), or did not provide a valid signed consent (n = 17). This left a total of 1464 patients and their samples for the assay comparisons.
One of the 8 study sites declined to administer the questionnaire concerning ease and preference of collection, and an additional 172 women across all the other sites either declined to complete it or provided an incomplete form, which eliminated appropriate comparisons. This provided a total of 1090 completed forms.
Each of the 8 sites obtained Investigational Review Board approval, which required written or oral informed consent before recording of patient information and specimen collection.
Patient-Collected Vaginal Swab Ease and Preference Survey
After all specimens were collected, subjects were asked to answer 15 questions using a 5-point Likert scale to indicate how easy or difficult it was to read the vaginal swab collection instructions, understand the vaginal swab self-collection instructions, understand the diagrams, and use the vaginal swab. They were also asked additional dichotomous questions to indicate their highest level of education achieved and whether English was their second language. They answered yes or no to whether they had ever been tested for an STI and whether they had ever had gonorrhea, chlamydia, or trichomoniasis; or had more than one sex partner in the past 6 months. Other questions included whether they had ever 1) used tampons, 2) looked at their vagina, 3) used a diaphragm, 4) used a vaginal swab before, or 5) been pregnant. To determine preference, they were asked whether they preferred a vaginal swab over a pelvic examination or urine collection and whether they would test themselves more often if a vaginal swab was available.
Specimen Collection and Processing
Five different specimens were collected from each enrollee. The patient collected urine and a vaginal swab. Gen-Probe Incorporated provided illustrated instructions for both patient and clinician vaginal swab collections (Fig. 1). Subjects were allowed to choose whether a nurse or clinician supervised their own vaginal swab collection and whether they wanted to perform the collection standing or sitting. Vaginal swabs and urine were collected in the clinic followed by the clinician collection of another vaginal swab and 2 randomized cervical swabs.
Data Management and Analysis
Data from the survey in ease and preference of collection were analyzed and frequency distributions and averages were calculated for each of the 4 questions in each of the following 5 categories: very easy, somewhat easy, neither easy nor difficult, somewhat difficult, and very difficult. Results were stratified by demographics such as age, education level, English as a second language, clinical study site, and whether a nurse was present.
Ease and Preference for Self-Sampling
Of the 1330 women surveyed, 1090 (82%) completed the ease and preference questionnaire. The average age of the 1090 women was 26.6 years (range, 15–71 years). Racially, 59.6% were black, 25.5% white, 11% Hispanic, 1.9% Asian, and 2% unknown. Most of the women had come to the clinic for an STI screen (57.9%); an additional 22.6% for an annual examination and the rest for reasons such as infertility, contact tracing, or a prenatal workup. In answer to the questions on experience, 35.1% had more than one sex partner in the past 6 months, 84.9% had been previously tested for an STI, and 49.2% had experienced an STI (34.4% GC, 57.4% CT, and 42.5% trichomoniasis). Only 5.3% had ever used a diaphragm, but 16.2% had previously self-collected a vaginal swab and 87% indicated that they had looked at their vagina. A total of 63.3% had been pregnant.
Table 1illustrates that 89.6% of women found that it was very easy to collect their own vaginal swab (range, 98.1–83.6%). Although “somewhat easy” or “neither easy nor difficult” was the option chosen by small numbers of patients across sites, very few women expressed difficulty in collecting their own vaginal swab. Similarly, these women found it very easy to follow, read, and understand the instructions.
In answer to the ease or difficulty related to the steps in the self-collection process, over 90% of the subjects reported that handling the swabs and tubes was very easy. Inserting, rotating, and withdrawing the swab was very easy for 84%, but an additional 10% indicated that this part of the instructions was somewhat easy (data not shown).
Examination of the effect of age on ease of collection of a vaginal swab indicated over 90% of the women in each age group found the procedure to be very easy or somewhat easy. Similarly, the level of education did not affect the ease of collection scores (data not shown).
Sampling preference showed that 76% preferred a vaginal swab over a pelvic examination and 60% over a urine collection. When asked “Would you test yourself more often for an STI if the self-collected vaginal swab was available?,” 94% answered “yes.”
Of the 1464 subjects who collected their own vaginal swab, 881 (60.2%) did it while standing, 579 while seated, 3 lying down, and one unknown. Self-collection position did not significantly affect the ability to detect an infected patient (seated—CT 98.3%; GC 100%; standing—CT 95.8%; GC 98.1%) and did not impact on ease or preference of self-collection (data not shown).
This multicentered study, which questioned women from 7 regions in North America, demonstrated that, given a set of clear instructions, a majority of women found it very easy to collect their own vaginal swabs, which, when tested in the combined NAA assay (AC2), yielded highly accurate results for the diagnosis of C. trachomatis and N. gonorrhoeae infections of the lower genital tract. The results of testing self-collected vaginal swabs were almost identical to those achieved by the sample collected by the clinician. The ability of patients to do as well as clinicians when collecting their own vaginal swabs for CT or GC diagnosis has been observed in other studies.13,19 Variations in ease of collection were minimal from one clinical setting to another for following, reading, and understanding collection instructions and using the vaginal swab. When questioned about preference; 76% of the women preferred a vaginal swab over a pelvic examination and 60% over a urine; 94% answered that they would get tested more often for an STI if self-collection of a vaginal swab was available. Our study and several recent publications15–18 indicate that most women preferred a self-sampling approach to diagnose an STI over a clinician-collected sample that required a pelvic examination. Our study also showed that a vaginal swab was preferred over both a urine sample and a cervical swab. This was different from a study by Newman15 on preferences of collection methods in female prisoners, which showed that approximately 30% of participants said they would prefer to give a swab specimen in the future rather than collect urine, but nearly half expressed no preference in one over the other. Richardson17 found that women attending street and student health clinics showed a greater preference for collecting their own vaginal swab than those attending family physician offices, birth control clinics, or STD clinics. However, some studies have found a patient preference for collecting urine. In female army recruits, Hsieh et al18 found that more women would prefer urine collection over self-administered vaginal swabs both in the field and at home, and that women of races other than white had less preference for the vaginal swab and felt more uncomfortable using it. Serlin et al16 found that adolescents attending university or HMO clinics in San Francisco ranked urine collection slightly more favorably than vaginal swabbing and that 25% of participants refused to collect vaginal swabs giving reasons of “lack of time” or “lack of trust” in the new technique. There may be several reasons why patients might prefer one less-invasive procedure over another for the diagnosis of STIs, including experience with their own anatomy, how simplified the collection process is made,19 experience with collecting the first 20 mL of urine, voluntary ease of urination when asked to, perception of whether a patient-collected sample is reliable,20 or the physical well-being felt during an initial pelvic examination. Perhaps the care we took in providing a clear set of instructions, together with a diagram, had an influence on the patients’ preferences.
Age and level of education did not influence the ease and preference outcomes in our study. Similarly, there was very little variation of ease and preference from one clinical site to another, except for the University of Alabama clinics, where 83.6% of respondents scored the collection process as “very easy” (approximately 10% lower than the other sites), but an additional 11.1% said it was “somewhat easy.”
The multiplex AC2 Assay performed on urine has been shown to be equally effective to testing cervical swabs in detecting patients infected with CT and slightly less effective in diagnosing GC.21 Vaginal swabs and urines tested by NAA assays have been shown to be effective in identifying women infected with CT and GC. Our studies have shown that the AC2 Assay performed on vaginal swabs identified as many or more patients infected with CT and/or GC as cervical swabbing.23 In symptomatic women in whom speculum examinations are indicated, collection of both sample types may enhance the diagnosis. Like most other studies comparing vaginal swabs with urine, more positive patients were identified with the vaginal swabs in our study. In the multicentered study published by Schachter et al,13 both TMA and PCR performed on vaginal swabs identified 24.4% and 16.3% more cases of CT than the urine sample, whereas both samples were equally efficient in the LCR test. Using LCR on samples from female army recruits, Hsieh et al18 found that the urine sample yielded 6.6% more chlamydial infections than vaginal swabs. The observations of Shafer et al14 using the LCR test were similar to ours with AC2 in which vaginal swabs consistently identified more cases of CT and GC than the urine specimen. These observations of differences in the ability of these less-invasive sampling procedures to identify infected patients may be the result of inhibitors in the samples, which are specific for the NAA test used22–25 or may reflect the amount of target nucleic acid present, which may be influenced by the site of infection.
The AC2 assay is very sensitive and specific when performed on noninvasive samples such as vaginal swabs. Women of all ages and backgrounds found it very easy and preferred to collect their own vaginal sample to diagnose CT and GC. These observations should enhance the implementation of screening programs for these STIs.
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