Literature review > Issue_5 > Review on Koumas et al. 

The ability to perform multiple tests on a single specimen, such as that used for liquid-based cervical cytology (LBC), is attractive. Oncogenic human papillomavirus (HPV) testing of the remaining LBC sample is now an optional 'reflex' procedure to guide the triage of a woman whose cervical cytology shows atypical cells of undetermined significance (ASCUS) [1]. Koumans and colleagues have now strengthened the evidence that the methanol-based PreservCyt (Cytyc Corp., Boxborough, Mass.) LBC fixative solution supports multiplex testing since it preserved the nucleic acids of Chlamydia trachomatis and Neisseria gonorrhoeae under various storage conditions. Accordingly, at least one commercially available nucleic acid amplification test for both organisms is now licensed for use with PreservCyt specimens (COBAS AMPLICOR, Roche Diagnostic Systems, Branchburg, N.J.).

If methanol itself is the essential ingredient for storage of nucleic acids, then it is conceivable that methanol could be used as an inexpensive storage medium for organisms and their nucleic acids in genitourinary specimens. Importantly, this potentially removes the requirement to link acquisition of specimens with LBC activities and renders irrelevant any debate about the cost effectiveness of LBC and conventional cytology [2]. This study shows another potential shortcoming of linking multiplex testing with LBC - the amount of specimen left over after LBC had been done. The remaining specimen volume was inadequate for testing beyond LBC in 12% (36/291) of the young women in this study. This is a shortcoming of any strategy based on LBC and it needs to be addressed.

The agreement between specimens stored in PreservCyt and those in proprietary test media for C. trachomatis or N. gonorrhoeae was assessed conservatively using the kappa statistic to determine residual agreement after agreement expected due to chance is removed. Overall, the levels of agreement were excellent. The problem of false positives, i.e., lower specificity, in NAAT for C. trachomatis in contrast to N. gonorrhoeae was consistently present with specimens stored in PreservCyt and with those stored in a proprietary transport medium (LCx, Abbott Laboratories, Chicago, Ill.). There does not seem to be any suggestion from these data that contamination among specimens occurs during the LBC procedure prior to performing a NAAT for C. trachomatis.

A strength of this study, which increases its internal and external validity, is the prospective, simultaneous collection of specimens from women within the age group of interest for C. trachomatis screening. In future research it would be of interest to know if there is any association between the two bacterial infections and inflammation on LBC [3], as this might support a selective use of reflex testing for infection just as the finding of ASCUS does for HPV testing. Continued research and test development are needed to resolve the remaining technical problems with multiplex testing for C. trachomatis and N. gonorrhoeae and to identify the most effective and efficient screening strategies based on a common specimen that can be tested in multiple ways.

Reference:

1. Wright TC, Cox JT, Massad LS, Twiggs LB, Wilkinson EJ. 2001 consensus guidelines for the management of women with cervical cytological abnormalities. J Amer Med Assoc 2002;287:2120-9.

2. McCrory DC, Mather DB, Bastian L et al. Evaluation of cervical cytology. Evidence Report/Technology Assessment No. 5. AHCPR Publication No. 99-E010. Rockville, MD: Agency for Health Care Policy and Research. February 1999.

3. Anguenot JL, de Marval F, Vassilakos P, Auckenthaler R, Ibecheole V, Campana A. Combined screening for Chlamydia trachomatis and squamous intra-epithelial lesions using a single liquid-based cervical sample. Hum Reprod 2001;16:2206-10.

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