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Use of combined chlamydia testing and cervical cytology

Interest in combined cervical cancer and chlamydia screening stems from the realisation that STD clinic-based testing is probably not going to be sufficient to control chlamydial genital tract infection. In many countries, women already undergo regular cervical examination for cervical cancer screening, so why not take advantage of the opportunity? This is not a new concept. The FDA approved adjunctive testing of human papilloma virus (a sexually transmitted infection) from cervical cytology specimens some years ago. A paper on the potential of concurrent testing for chlamydia and cervical abnormalities was published by Lentrichia et al., in 1998. However cervical cancer screening is primarily focussed at older women whereas chlamydial genital tract infection is most prevalent in women aged 18 to 25 years, so feasibility and cost benefit studies are clearly required.

The original paper of  Lentrichia et al., 1998 was subsequently extended  [Imhorn et al., 2001].   Cervical scrapings were collected for the ThinPrep Papanicolau cervical cytology test and then a second swab was used to collect an endocervical sample for conventional diagnostic chlamydial direct fluorescence assay (DFA). The DFA slide prepared from the ThinPrep cytology fluid and the conventional DFA sample were evaluated independently in a blinded, multi-centre study. Residual specimen from discrepant cases were revaluated by direct Chlamydia DNA testing. On 636 cases, 582 (91.5%) were negative on both slides, 43 (6.8%) positive by both and 11 (1.7%) discrepant. The prevalence of C. trachomatis infection by conventional DFA was  7.9%. There was no statistical differences between the two tests [Imhorn et al., 2001].

Anguenot et al 2001 were concerned that cervicitis might alter cytological interpretation and thus might compromise a combined screening for chlamydial cervicitis and cervical neoplasia. However they point out that liquid-based cytological methods are believed to limit obscuring factors as well as permiting the detection of sexually transmitted infections agents by DNA amplification. Accordingly they obtained two cervical samples from 590 women considered at high risk for genital chlamydial infection and compared the conventional Abbott LCx method with a modified LCx based on specimens collected in the AutoCyte^® cytology preservative fluid. They found total agreement for 588 of 590 cervical samples using the two LCR protocols (Kappa = 0.96; 95% confidence interval: 0.91-1.00). Furthermore the quality of cervical cytology was not compromised by chlamydial cervicitis.

In a large study, Bianchi et al., 2002 in France used the Roche COBAS AMPLICOR CT/NG PCR test to detect C. trachomatis infection in PreservCyt^® transport medium (Cytyc Corporation, US) from 22 of 1000 women aged 15 to 25 years undergoing routine cervical cytology screening. Only 9 of these 22 positive women agreed to retesting by conventional COBAS AMPLICOR PCR using material collected into sucrose phosphate chlamydia transport buffer, but all 9 of these women were again positive. Chlamydial DNA was found to be stable in PreservCyt transport medium for at least 6 weeks at room temperature. These authors presented their results at the IUSTI-Europe 2002 conference in Vienna and kindly agreed to their presentation being reproduced below [see figures 1 - 16].

Figure 1. Title slide, presentation made by Dr A Bianchi at IUSTI-Europe 2002, Vienna. Presented here by courtesy of the authors. © Bianchi et al., 2002.	Figure 2. Sexually active young women also need to be monitored for pre-cancerous lesions of the cervix.	Figure 3. The aim of the study.	Figure 4. Protocol for preliminary laboratory testing of PreservCyt medium versus chlamydial 2SP transport buffer as a basis for COBAS AMPLICOR PCR.
Figure 5. The study population.	Figure 6. Specimen processing.	Figure 7. Protocol for testing the stability of chlamydial DNA at room temperature in cytology medium over 6 weeks.	Figure 8. Results of preliminary laboratory testing. Cytology medium did not cause inhibition of AMPLICOR PCR amplification.
Figure 9.Laboratory testing: detection sensitivity	Figure 10. Detection limit for C. trachomatis was 10 inclusion forming units per ml.	Figure 11. 22 of 1000 asymptomatic women with normal cytology were positive for C. trachomatis.	Figure 12. Chlamydial DNA was stable for at least 6 weeks at room temperature when stored in cytology medium.
Figure 13. Other studies.	Figure 14. Storage of DNAin cytology media.	Figure 15. Conclusion: combined STI and cervical cytology testing is feasible.	Figure 16. Collaborators and acknowledgements.

Cytology media can also be used for the storage and detection of RNA [Dimulescu et al., 1998]. It remains to be determined whether these media are suitable for diagnostic tests based on chlamydial RNA.

[MEW November 2002].

[MEW Comment: The feasibility of using DNA amplification based tests for the diagnosis of chlamydial genital tract infection on material collected in cervical cytology transport media has been clearly demonstrated. More studies are needed to define whether there is any loss of diagnostic sensitivity inherent in this approach. Furthermore, studies are needed to define the cost and public health benefits of simultaneously screening for chlamydial infection and abnormal cervical cytology. Screening at cytology clinic has the potential to reach new populations. However, dependent on local circumstances, combined screening is probably only justified from the chlamydial viewpoint for 'at risk' women, mainly those in the sexually active 15 to 25 age group. However this age group is not at high risk of cervical neoplasia and is often poorly covered by cervical cancer screening programs. Public health economists will need to model the benefits carefully. Conversely, as Bianchi and colleagues point out, sexually active older women attending an STD clinic should have a cervical cytology screen if they have not recently had one. In this case the ability to perform combined STI and cancer screening on the same sample may be very useful].

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References

Inhorn, S. L., Wand, P. J., Wright, T. C., Hatch, K. D., Hallum, J. & Lentrichia, B. B. (2001). Chlamydia trachomatis and Pap testing from a single, fluid-based sample. A multicenter study. Journal of Reproductive Medicine 46, 237 - 242.

Lentrichia, B. B., Hecht, S. S., Lapen, D. & Corkill, M. K. (1998). Potential for routine concurrent determination of chlamydia and cervical abnormalities by single fluid-based sampling. Primary Care Update in Obstetrics and Gynaecology 5, 149 - 150.

[MEW November 2002]