Short Communication
Mouthwash as a Low-Cost and Safe Specimen Transport
Medium for Human Papillomavirus DNA Testing of
Cervicovaginal Specimens
Philip E. Castle,
1
Mark Sadorra,
2
Francisco A.R. Garcia,
3
Allison P. Cullen,
4
Attila T. Lorincz,
4
Amy L. Mitchell,
3
Denise Whitby,
5
Ronald Chuke,
4
and Janet R. Kornegay
2
1
Division of Cancer Epidemiology, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland;
2
Roche Molecular Systems, Alameda, California;
3
University of Arizona Health Sciences Center, Tucson, Arizona;
4
Digene Corporation,
Gaithersburg, Maryland; and
5
Science Applications International Corporation-Frederick, Frederick, Maryland
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 z94% total agreement and k values of z0.88
between media at each time point for PCR-detected
carcinogenic HPV. We observed a z74% total agreement,
z0.62 unweighted k , and z0.75 linearly weighted k
between media at each time point for PCR-detected HPV
cancer risk category. Finally, we observed an 88% total
agreement and k 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 f15
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
840
Cancer Epidemiol Biomarkers Prev 2007;16(4). April 2007
Received 10/27/06; revised 1/8/07; accepted 1/29/07.
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.
Requests for reprints: Philip E. Castle, Division of Cancer Epidemiology and Genetics,
National Cancer Institute, 6120 Executive Boulevard, Room 5004, EPS MSC 7234, Bethesda,
MD 20892-7234. Phone: 301-435-3976; Fax: 301-402-0916. E-mail: castlep@mail.nih.gov
Copyright D 2007 American Association for Cancer Research.
doi:10.1158/1055-9965.EPI-06-0909
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