Abstract
The usefulness of mouthwash as a transport medium for cervical specimens for carcinogenic human papillomavirus (HPV) DNA testing has not been evaluated. Two cervical specimens were collected from each of 34 patients, with one placed in mouthwash (Scope, Proctor and Gamble, Inc.) and the other in a liquid cytology medium commonly used for HPV DNA testing in alternating order. Paired specimens were tested by a PCR assay for carcinogenic HPV and a PCR HPV genotyping assay for 37 HPV types at 0, 3, and 6 weeks after collection; the results of the HPV genotyping assay were categorized into HPV risk groups according to cancer risk (HPV-16 > HPV-18 > other carcinogenic HPV types > noncarcinogenic HPV types > negative). After 4 months of storage, specimens were tested using a second, non-PCR test for carcinogenic HPV. We observed a ≥94% total agreement and κ values of ≥0.88 between media at each time point for PCR-detected carcinogenic HPV. We observed a ≥74% total agreement, ≥0.62 unweighted κ, and ≥0.75 linearly weighted κ between media at each time point for PCR-detected HPV cancer risk category. Finally, we observed an 88% total agreement and κ of 0.77 between media for carcinogenic HPV detection using a second test after 4 months of storage. We suggest that mouthwash might be used as a low-cost, safe, nonflammable storage and transport medium for cervical specimens for HPV DNA testing in cervical cancer screening programs. (Cancer Epidemiol Biomarkers Prev 2007;16(4):840–3)
Introduction
Cervical cancer screening using Papanicolaou (Pap) smears or cytology has significantly reduced the incidence and mortality of cervical cancer where effective programs have been instituted (1). However, arguably, cytology has reached its limits in global effect on cervical cancer incidence and mortality. Cytology is an insensitive test for the detection of precancerous lesions (2) and is poorly reproducible (3). Its effectiveness in screening programs is the consequence of repeated screening to detect precancerous lesions during their slow progression to cervical cancer. The cervical cancer prevention program in the United States based on cytology screening, as successful as it is, comes at a significant price of $6 billion or more annually (4). The cost ineffectiveness of this program makes it unlikely for effective adoption in resource-limited regions.
It is now widely recognized that cervical infections by ∼15 cancer-associated (carcinogenic) human papillomavirus (HPV) infections cause virtually all cervical cancer (5-7) and its immediate precursor, precancerous lesions (8). It is the failure to clear HPV infections and the subsequent progression of persistent carcinogenic HPV infections that are the key steps in cervical carcinogenesis (9). Based on this central role of persistent carcinogenic HPV infections in the development of cervical cancer, DNA tests for carcinogenic HPV have been developed, and one has been approved for use by the Food and Drug Administration. HPV DNA testing has proved to be more accurate, with greater sensitivity albeit slightly less specificity, than cervical cytology (2), and is much more reliable (10, 11).
The improved clinical performance of HPV DNA testing compared with cervical cytology might be used to expand coverage of cervical cancer screening programs by combining self-collection of cervicovaginal specimens with HPV DNA testing. Self-collection with HPV DNA testing could be used to overcome some barriers to participation in screening programs such as the unwillingness of women to undergo pelvic exams or unwillingness to attending a screening clinic due to geographic or financial barriers. It can also reduce the cost and burden at the clinic by reducing the number of patients attending primary screening.
Overcoming these barriers could be the most challenging, especially for women living in rural regions. However, with self-collection at home, it is important to maximize safety while preserving the specimen for many days until its return by mail or self-delivery to the laboratory for testing. Although liquid cytology medium might preserve a self-collected specimen for many days until a woman either mailed or self-delivered the specimen to the clinic or clinical lab, the toxicities of these buffers make their presence in the homes of reproductive-age women unacceptable.
A safe and inexpensive method for the preservation of self-collected specimens is needed. Mouthwash has been used to collect buccal cells for genetic epidemiologic studies (12) and could be a potential preservative of cervical specimens for HPV DNA testing. Therefore, we undertook a preliminary study to compare detection of HPV DNA in mouthwash to a liquid cytology medium commonly used for HPV DNA testing.
Materials and Methods
Cervical Specimens and Data
Thirty-four women attending a colposcopy clinic at the Women's Health and Resource Center at the University of Arizona for cytologic abnormalities were enrolled. Anonymized, paired cervical specimens were collected using Dacron swabs and one was placed in PreservCyt (Cytyc Corp., Marlborough, MA) and the other in Scope (Proctor and Gamble, Cincinnati, OH) in alternating order. Specimens were collected using Dacron swabs, and the collection order was alternated to control for any effects due to the order of collection. On collection, specimens were stored at ambient temperature for ≤3 h and then refrigerated (5°C) until shipped via a commercial courier at ambient temperature to the testing lab. The institutional Review Board of University of Arizona approved the study, and the use of these specimens was deemed exempt from review by National Cancer Institute Institutional Review Board.
HPV Testing
One aliquot from each specimen was tested using the commercially available Linear Array HPV genotyping test (Roche Molecular Systems, Alameda, CA) and another aliquot by AMPLICOR MWP assay (Roche) according to the manufacturer's instructions in the product insert. Briefly, DNA was extracted from clinical specimen aliquots using the QIAamp MinElute Media Kit (Qiagen, Inc., Valencia, CA), and target DNA amplified by PCR. Linear Array uses the PGMY09/11 L1 consensus primer system and includes coamplification of a human cellular target, β-globin, as an internal control. Detection and HPV genotyping are achieved using a reverse line-blot method and this test includes probes to genotype for 37 anogenital HPV types [6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 45, 51-56, 58, 59, 61, 62, 64, 66-73, 81, 82 subtype (IS39), 82 subtype (W13b), 83, 84, and 89]. In some multitype infections, the presence of HPV-52 cannot be confirmed or ruled out (i.e., a band appears, which could be the result of a HPV-52 infection or to cross-reactivity). MWP (also known as AMPLICOR) is a PCR amplification test that detects a pool of 13 carcinogenic HPV types (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) without distinguishing the type (13, 14). A positive cutoff point of 0.2 was used.
The only deviation from the Linear Array and MWP product insert protocol was to implement an automated sample preparation for extraction of up to 96 specimens at a time on the Qiagen MDx platform (using the MinElute Media MDx Kit and manufacturer's instructions) rather than processing 24 specimens per batch with the manual vacuum method. Results from specimens that failed to amplify the β-globin internal control, indicating poor DNA recovery and an invalid sample, were excluded from the study. Specimens in both media were stored at ambient temperature and aliquots were drawn on days 0, 21, and 42 for DNA purification and testing by Linear Array and MWP.
Residual specimens6
Collection of specimens using Dacron swabs is not an approved method for clinical testing by Hybrid Capture 2 although this method of collection has been successfully used for Hybrid Capture 2 testing within natural history studies of HPV (16).
Statistics
Linear Array testing results were categorized hierarchically into groups according to cancer risk (HPV-16 > HPV-18 > other carcinogenic HPV types > noncarcinogenic HPV types > PCR negative; HPV cancer risk group).
We compared the agreement for detection of carcinogenic HPV and HPV risk groups by calculating κ statistics (unweighted and linearly weighted) and crude agreement. We tested for statistical differences in test positivity using the McNemar's χ2 test. Spearman correlation coefficient was calculated for signal strengths of paired results. Wilcoxon sign-rank test was used to test for differences in Hybrid Capture 2 signal strength, a semiquantitative measure of HPV viral load (17), between paired specimens.
General estimating equations were used to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for the comparison of paired results at all testing (storage) times for either Linear Array or MWP for specimens stored in the two media, controlling for storage times and the order of collection.
Results
A comparison of MWP test results for the paired PreservCyt and Scope specimens from 34 women is shown in Fig. 1. At each time point of testing the paired specimens, there was a ≥94% total agreement and κ values of ≥0.88 for MWP results for carcinogenic HPV. There were no significant differences in testing positive for carcinogenic HPV for the specimens in each medium at each time point of testing.
MWP test results for carcinogenic HPV on paired PreservCyt (PC) and Scope specimens tested at time days 0, 21, and 42. Signal strength is shown on the left (▴, day 0; □, day 21; +, day 42) and the tabulation of the results is shown on the right. A positive cutoff point of 0.2 signal strength was used. The circled results represent the day 0, day 21, and day 42 discordant test results for paired specimens from one patient.
MWP test results for carcinogenic HPV on paired PreservCyt (PC) and Scope specimens tested at time days 0, 21, and 42. Signal strength is shown on the left (▴, day 0; □, day 21; +, day 42) and the tabulation of the results is shown on the right. A positive cutoff point of 0.2 signal strength was used. The circled results represent the day 0, day 21, and day 42 discordant test results for paired specimens from one patient.
When we compared the results of HPV genotyping as detected by Linear Array and ranked hierarchically according to cancer risk (Table 1), there was a ≥74% total agreement, ≥0.62 unweighted κ, and ≥0.75 linearly weighted κ at each time point of testing for both media. There were no significant differences between specimens in each medium at each time point of testing for HPV cancer risk group. A comparison between the two media of the combined results of HPV types detected for the three tests done at different time points is shown in Table 2.
Linear Array results for HPV genotypes, categorized according to HPV risk group (HPV-16 > HPV-18 > carcinogenic HPV types other than HPV-16 and HPV-18, noncarcinogenic HPV types, PCR negative) on paired PreservCyt and Scope specimens tested at days 0, 21, and 42
PreservCyt . | Scope . | . | . | . | . | . | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
. | PCR− . | Noncarc . | Carc . | HPV-18 . | HPV-16 . | Total . | ||||||
Day 0 | ||||||||||||
PCR− | 9 | 0 | 1 | 0 | 0 | 10 | ||||||
Noncarc | 2 | 2 | 0 | 0 | 0 | 4 | ||||||
Carc | 2 | 1 | 11 | 0 | 0 | 14 | ||||||
HPV-18 | 0 | 0 | 1 | 1 | 0 | 2 | ||||||
HPV-16 | 0 | 0 | 0 | 0 | 4 | 4 | ||||||
Total | 13 | 3 | 13 | 1 | 4 | 34 | ||||||
Agreement, 79%; κ = 0.71; weighted κ = 0.79; P = 0.6 | ||||||||||||
Day 21 | ||||||||||||
PCR− | 9 | 2 | 1 | 0 | 0 | 12 | ||||||
Noncarc | 1 | 2 | 1 | 0 | 0 | 4 | ||||||
Carc | 2 | 0 | 10 | 0 | 0 | 12 | ||||||
HPV-18 | 0 | 0 | 2 | 0 | 0 | 2 | ||||||
HPV-16 | 0 | 0 | 0 | 0 | 4 | 4 | ||||||
Total | 12 | 4 | 14 | 0 | 4 | 34 | ||||||
Agreement, 74%; κ = 0.62; weighted κ = 0.75; P = 0.7 | ||||||||||||
Day 42 | ||||||||||||
PCR− | 9 | 2 | 1 | 0 | 0 | 12 | ||||||
Noncarc | 2 | 1 | 0 | 0 | 0 | 3 | ||||||
Carc | 1 | 1 | 11 | 0 | 0 | 13 | ||||||
HPV-18 | 0 | 0 | 1 | 1 | 0 | 2 | ||||||
HPV-16 | 0 | 0 | 0 | 0 | 4 | 4 | ||||||
Total | 12 | 4 | 12 | 1 | 4 | 34 | ||||||
Agreement, 76%; κ = 0.67; weighted κ = 0.79; P = 1.0 |
PreservCyt . | Scope . | . | . | . | . | . | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
. | PCR− . | Noncarc . | Carc . | HPV-18 . | HPV-16 . | Total . | ||||||
Day 0 | ||||||||||||
PCR− | 9 | 0 | 1 | 0 | 0 | 10 | ||||||
Noncarc | 2 | 2 | 0 | 0 | 0 | 4 | ||||||
Carc | 2 | 1 | 11 | 0 | 0 | 14 | ||||||
HPV-18 | 0 | 0 | 1 | 1 | 0 | 2 | ||||||
HPV-16 | 0 | 0 | 0 | 0 | 4 | 4 | ||||||
Total | 13 | 3 | 13 | 1 | 4 | 34 | ||||||
Agreement, 79%; κ = 0.71; weighted κ = 0.79; P = 0.6 | ||||||||||||
Day 21 | ||||||||||||
PCR− | 9 | 2 | 1 | 0 | 0 | 12 | ||||||
Noncarc | 1 | 2 | 1 | 0 | 0 | 4 | ||||||
Carc | 2 | 0 | 10 | 0 | 0 | 12 | ||||||
HPV-18 | 0 | 0 | 2 | 0 | 0 | 2 | ||||||
HPV-16 | 0 | 0 | 0 | 0 | 4 | 4 | ||||||
Total | 12 | 4 | 14 | 0 | 4 | 34 | ||||||
Agreement, 74%; κ = 0.62; weighted κ = 0.75; P = 0.7 | ||||||||||||
Day 42 | ||||||||||||
PCR− | 9 | 2 | 1 | 0 | 0 | 12 | ||||||
Noncarc | 2 | 1 | 0 | 0 | 0 | 3 | ||||||
Carc | 1 | 1 | 11 | 0 | 0 | 13 | ||||||
HPV-18 | 0 | 0 | 1 | 1 | 0 | 2 | ||||||
HPV-16 | 0 | 0 | 0 | 0 | 4 | 4 | ||||||
Total | 12 | 4 | 12 | 1 | 4 | 34 | ||||||
Agreement, 76%; κ = 0.67; weighted κ = 0.79; P = 1.0 |
Abbreviations: Carc, carcinogenic HPV types other than HPV-16 and HPV-18; Noncarc, noncarcinogenic HPV types; PCR−, PCR negative.
The combined linear array results for HPV genotypes on paired PreservCyt and Scope specimens for the three tests at different time points (days 0, 21, and 42)
. | Scope, n (%) . | PreservCyt, n (%) . |
---|---|---|
HPV-16 | 4 (12) | 4 (12) |
HPV-18 | 1 (3) | 2 (6) |
HPV-31 | 5 (15) | 6 (18) |
HPV-33 | 2 (6) | 3 (9) |
HPV-39 | 5 (15) | 4 (12) |
HPV-40 | 1 (3) | 1 (3) |
HPV-42 | 2 (6) | 2 (6) |
HPV-51 | 3 (9) | 4 (12) |
HPV-52* | 2 (6) | 2 (6) |
HPV-53 | 2 (6) | 3 (9) |
HPV-54 | 0 (0) | 1 (3) |
HPV-55 | 1 (3) | 2 (6) |
HPV-56 | 1 (3) | 1 (3) |
HPV-58 | 2 (6) | 1 (3) |
HPV-59 | 3 (9) | 2 (6) |
HPV-61 | 1 (3) | 2 (6) |
HPV-62 | 2 (6) | 3 (9) |
HPV-66 | 2 (6) | 2 (6) |
HPV-67 | 3 (9) | 3 (9) |
HPV-68 | 2 (6) | 2 (6) |
HPV-70 | 2 (6) | 1 (3) |
HPV-81 | 2 (6) | 0 (0) |
HPV-84 | 1 (3) | 0 (0) |
HPV-89 | 1 (3) | 0 (0) |
Total | 50 | 51 |
. | Scope, n (%) . | PreservCyt, n (%) . |
---|---|---|
HPV-16 | 4 (12) | 4 (12) |
HPV-18 | 1 (3) | 2 (6) |
HPV-31 | 5 (15) | 6 (18) |
HPV-33 | 2 (6) | 3 (9) |
HPV-39 | 5 (15) | 4 (12) |
HPV-40 | 1 (3) | 1 (3) |
HPV-42 | 2 (6) | 2 (6) |
HPV-51 | 3 (9) | 4 (12) |
HPV-52* | 2 (6) | 2 (6) |
HPV-53 | 2 (6) | 3 (9) |
HPV-54 | 0 (0) | 1 (3) |
HPV-55 | 1 (3) | 2 (6) |
HPV-56 | 1 (3) | 1 (3) |
HPV-58 | 2 (6) | 1 (3) |
HPV-59 | 3 (9) | 2 (6) |
HPV-61 | 1 (3) | 2 (6) |
HPV-62 | 2 (6) | 3 (9) |
HPV-66 | 2 (6) | 2 (6) |
HPV-67 | 3 (9) | 3 (9) |
HPV-68 | 2 (6) | 2 (6) |
HPV-70 | 2 (6) | 1 (3) |
HPV-81 | 2 (6) | 0 (0) |
HPV-84 | 1 (3) | 0 (0) |
HPV-89 | 1 (3) | 0 (0) |
Total | 50 | 51 |
NOTE: Types not detected in either specimen at any time point are not listed. (P = 1.0, Pearson χ2).
In some multitype infections, the presence of HPV-52 cannot be confirmed or ruled out, which occurred in four Scope specimens and three PreservCyt specimens.
To compare all test results for specimens in both media at all time points, we used general estimating equations to control for the autocorrelation of multiple test results from an assay on the same specimen and to adjust for covariates (storage time). Specimens in Scope were slightly less likely to test positive by MWP (OR, 0.86; 95% CI, 0.75-0.98; P = 0.02) than those in PreservCyt. The within-person correlation for these results was 0.94. Storage time was not associated with testing positive. Excluding one patient whose Scope specimen tested negative at all three time points and the PreservCyt specimen tested positive at all three time points (Fig. 1) negated this negative association with the Scope specimen (OR, 0.96; 95% CI, 0.88-1.0; P = 0.3) versus PreservCyt specimens, with a within-person correlation of 0.98. There were no significant differences for Linear Array test results between the paired specimens in the two media (data not shown).
Hybrid Capture 2 testing was conducted post hoc on these paired specimens 4 months after collection (13 mouthwash specimens leaked during transport to the testing lab; Fig. 2). The Spearman correlation of the Hybrid Capture 2 signal strength (relative light units per positive calibrator) was 0.91; among those specimens that either or both tested positive, the correlations were 0.81 or 0.68, respectively. There was an 88% total agreement and κ of 0.77 for Hybrid Capture 2 test results. There were no statistical differences in testing positive for carcinogenic HPV for the specimens in each medium (P = 0.6). There were no statistical differences in the signal strength for all paired specimens (P = 0.5), for those specimens in which at least one tested positive (P = 0.9), and for those specimens in which both tested positive (P = 0.9). The aforementioned pair of specimens from a patient for whom the Scope specimen tested negative at all time points whereas the PreservCyt specimen tested positive at all time points by Linear Array and MWP tested negative by Hybrid Capture 2 (i.e., there was no discordance between the two specimen types).
Hybrid Capture 2 test results for carcinogenic HPV on paired PreservCyt and Scope specimens. Signal strengths (RLU/pc) are shown in the graph. Inset, tabulation of the paired [negative (Neg) or positive (Pos)] test results; a signal strength of 1.0 RLU/pc was used as the positive cutoff point. PC, PreservCyt. Open symbols, specimen leaked in transit to the testing laboratory. Percent agreement, 88%; κ = 0.77; P = 0.6.
Hybrid Capture 2 test results for carcinogenic HPV on paired PreservCyt and Scope specimens. Signal strengths (RLU/pc) are shown in the graph. Inset, tabulation of the paired [negative (Neg) or positive (Pos)] test results; a signal strength of 1.0 RLU/pc was used as the positive cutoff point. PC, PreservCyt. Open symbols, specimen leaked in transit to the testing laboratory. Percent agreement, 88%; κ = 0.77; P = 0.6.
Two patients were diagnosed with histologic cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and three patients were diagnosed with histologic CIN2 (Table 3). For patients with CIN3/CIS, both specimens tested positive for carcinogenic HPV at all three time points by both PCR tests and tested positive for carcinogenic HPV by Hybrid Capture 2 after 4 months. Both specimens from patients diagnosed with CIN2, a less certain diagnosis of cervical precancer (3), were positive for carcinogenic HPV by MWP at all three time points but the test results for Linear Array at the three time points and for post hoc Hybrid Capture 2 testing were variable. One possible explanation is that the CIN2 lesions were relatively small and therefore had a lower viral load, resulting in more variable test results in less analytically sensitive assays.
Results from MWP, Linear Array, and Hybrid Capture 2 testing of cases of histologic CIN2 or CIN3/CIS for paired specimens in Scope and PreservCyt
ID . | Histology . | MWP . | . | . | . | . | . | Linear Array . | . | . | . | . | . | Hybrid Capture 2 . | . | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | . | Scope . | . | . | PreservCyt . | . | . | Scope . | . | . | PreservCyt . | . | . | Scope . | PreservCyt . | |||||||||||
. | . | Day 0 . | Day 21 . | Day 42 . | Day 0 . | Day 21 . | Day 42 . | Day 0 . | Day 21 . | Day 42 . | Day 0 . | Day 21 . | Day 42 . | . | . | |||||||||||
SP005 | CIN3/CIS | + | + | + | + | + | + | 31 | 31 | 31 | 31 | 31 | 31 | + | + | |||||||||||
SP018 | CIN3/CIS | + | + | + | + | + | + | 16 | 16 | 16 | 16, 42 | 16, 42 | 16, 42 | + | + | |||||||||||
SP020 | CIN2 | + | + | + | + | + | + | 16 | 16 | 16 | 16 | 16 | 16 | + | — | |||||||||||
SP023 | CIN2 | + | + | + | + | + | + | 42, 81, 84, 89 | 42, 81, 89 | 42, 81, 84, 89 | 52 | — | — | + | + | |||||||||||
SP039 | CIN2 | + | + | + | + | + | + | — | — | 31, 66 | 66 | 31, 66 | 31, 66 | — | — |
ID . | Histology . | MWP . | . | . | . | . | . | Linear Array . | . | . | . | . | . | Hybrid Capture 2 . | . | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | . | Scope . | . | . | PreservCyt . | . | . | Scope . | . | . | PreservCyt . | . | . | Scope . | PreservCyt . | |||||||||||
. | . | Day 0 . | Day 21 . | Day 42 . | Day 0 . | Day 21 . | Day 42 . | Day 0 . | Day 21 . | Day 42 . | Day 0 . | Day 21 . | Day 42 . | . | . | |||||||||||
SP005 | CIN3/CIS | + | + | + | + | + | + | 31 | 31 | 31 | 31 | 31 | 31 | + | + | |||||||||||
SP018 | CIN3/CIS | + | + | + | + | + | + | 16 | 16 | 16 | 16, 42 | 16, 42 | 16, 42 | + | + | |||||||||||
SP020 | CIN2 | + | + | + | + | + | + | 16 | 16 | 16 | 16 | 16 | 16 | + | — | |||||||||||
SP023 | CIN2 | + | + | + | + | + | + | 42, 81, 84, 89 | 42, 81, 89 | 42, 81, 84, 89 | 52 | — | — | + | + | |||||||||||
SP039 | CIN2 | + | + | + | + | + | + | — | — | 31, 66 | 66 | 31, 66 | 31, 66 | — | — |
Discussion
In this study, we showed that HPV testing of cervical specimens stored in mouthwash was comparable to cervical specimens stored in PreservCyt, a liquid cytology medium commonly used for HPV DNA testing. We found very similar results using three different HPV assays, one signal amplification assay, and two target amplification (PCR) assays that use two different primer systems. Testing results by the two PCR-based assays seemed to be unaffected with storage time of >6 weeks, suggesting that both media preserved HPV DNA. After 4 months of storage, we found a very good agreement for Hybrid Capture 2 test results for the paired specimens, even with leakage of some mouthwash-preserved specimens in transport.
Based on limited data, we suggest that storage of cervical specimens in mouthwash such as Scope may be viable for HPV DNA testing and robust enough for low-resource settings, including accidental leakage and ambient temperature storage over many weeks. Thus, Scope could be used to transport either physician-collected specimens from outreach clinic or self-collected cervicovaginal from home to a central HPV testing laboratory. Scope also preserved tissue culture cells (data not shown), which raises the possibility that it could also be used for cervical cytology. Scope is low-cost, safe for accidental ingestion, nonflammable, and bacteriostatic. The composition of Scope includes two antiseptic compounds, cetylpyridinium chloride and sodium benzoate, and ∼20% ethanol, which possibly preserves HPV DNA in a similar fashion as the methanol does in PreservCyt. Other mouthwashes have different compositions, some with greater ethanol content. Although it is likely that these other ethanol-containing mouthwashes will perform similarly, they need independent confirmation including optimization for HPV DNA testing. In summary, we provide preliminary evidence that mouthwash might be useful as a transport/preservation medium for HPV DNA testing in cervical cancer screening. Further evaluations are warranted.
Grant support: Intramural Research Program of the NIH, National Cancer Institute.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.