Erin Ellison has challenged our contention that the false-negative rate for conventional Papanicolaou (Pap) smears is much higher than it is generally perceived to be.1 A recent meta-analysis conducted in primary screening settings indicated an average sensitivity of 51% (95% confidence interval 0.37–0.66).2 This figure will be shocking to anyone, like Ellison, whose knowledge base includes studies that were plagued by verification bias (also known as diagnostic workup bias) or involved the triage of equivocal or minor abnormalities, which are situations with a high prevalence of lesions. Screening sensitivity in studies affected by verification bias is invariably overestimated3 and should not be included in pooled overviews, a precaution that was taken in the aforementioned meta-analysis.2 In fact, it has been recommended that cost-effectiveness models of cervical cancer screening should be revised to use more conservative estimates of Pap test sensitivity.4
Ellison's arguments about the drawbacks of liquid-based cytology notwithstanding, this technique does represent an improvement over conventional smear techniques. The few studies that satisfy today's stringent criteria for quality of evidence have found liquid-based cytology to be significantly more sensitive than the conventional Pap test.2,5
The evidence for the effectiveness of the Pap test as a cancer control measure was obtained in an era before the randomized controlled trial paradigm became widespread. Newer techniques are being judged by criteria that are far more stringent than the ones used to place the Pap test on its current pedestal. Well-designed studies with suitable end points are expensive and take many years. Privileged observers of the cervical cancer screening scene, such as Ellison, should take this into account before prematurely repudiating new methods.
We agree that it is unfortunate that reliance on new technologies may limit the practice of cervical cancer screening to a few commercial interests. However, as these technologies gain ground, competition is likely to ensue and the present monopolies will disappear.
Signatures
Eduardo L. Franco
Departments of Oncology and Epidemiology McGill University Montreal, Que.
Eliane Duarte-Franco
Department of Oncology McGill University Montreal, Que.
Alex Ferenczy
Department of Pathology McGill University Montreal, Que.
References
- 1.Franco EL, Duarte-Franco E, Ferenczy A. Cervical cancer: epidemiology, prevention and the role of human papillomavirus infection. CMAJ 2001; 164(7):1017-25. [PMC free article] [PubMed]
- 2.McCrory DC, Matchar DB, Bastian L, Datta S, Hasselblad V, Hickey J, et al. Evaluation of cervical cytology. Evidence report/technology assessment no 5; AHCPR publ no 99-E010. Rockville (MD): Agency for Health Care Policy and Research; 1999. [PMC free article] [PubMed]
- 3.Franco EL. Statistical issues in human papillomavirus testing and screening. Clin Lab Med 2000; 20:345-67. [PubMed]
- 4.Nanda K, McCrory DC, Myers ER, Bastian LA, Hasselblad V, Hickey JD, et al. Accuracy of the Papanicolaou test in screening for and follow-up of cervical cytologic abnormalities: a systematic review. Ann Intern Med 2000;132:810-9. [DOI] [PubMed]
- 5.Hutchinson ML, Zahniser DJ, Sherman ME, Herrero R, Alfaro M, Bratti MC, et al. Utility of liquid-based cytology for cervical carcinoma screening: results of a population-based study conducted in a region of Costa Rica with a high incidence of cervical carcinoma. Cancer 1999; 87:48-55. [DOI] [PubMed]