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Screening for Cervical Cancer : an Overview

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Screening for Cervical Cancer : an Overview J Obstet Gynecol India Vol. 56, No. 2 : March/April 2006 Pg 115-122 REVIEW ARTICLE The Journal of Obstetrics and Gynecology of India Screening for cervical cancer : an overview Rajendra A Kerkar, Yogesh V Kulkarni Consultant, Division of Gynaecological Oncology, Tata Memorial Cancer Centre, Mumbai Key words : cervical cancer, screening methods, Pap smear, liquid based cytology, automated screening technology, HPV-DNA testing, visual inspection of cervix, speculoscopy, cervicography, polar proble, laser induced flurescence, compluter imaging Introduction one of the leading causes of cancer deaths amongst women. Cancer of the uterine cervix is a leading cause of mortality Nearly 400,000 new cases of cervical cancer are diagnosed annually worldwide and 80% of these are diagnosed in the and morbidity among women worldwide. In developing developing countries 1. There are 1.7 million prevalent cases countries it is the most common gynecological cancer and Normal cervix 80% regress HPV related changes 20% progress 60-80% regress Low grade SIL 15-20% progress within 2-3 years High grade SIL 30-70% progress in 10 years Invasive cervical cancer Figure 1. Progression from normal cervix to invasive cancer. Paper received on 08/12/2005 ; accepted on 06/02/2006 Correspondence : Dr. Rajendra A. Kerkar 31, Seville, St. Paul’s Road, Bandra West, Mumbai - 400 50. 115 Rajendra A Kerkar in the developing world and as many as 5-13 million women A variety of screening tests have therefore been developed have precancerous lesions 2. As the female population in the in an attempt to overcome the innate limitations of developing countries continues to rise with an increase in life conventional cytology. These are currently under evaluation expectancy, the proportion of older women will also and it is hoped that they may improve upon the accuracy of necessarily rise. It is expected that the number of cases of conventional screening cytology. cancer cervix will rise further in the years to come. Screening tests for cervical carcinoma Natural history of cervical carcinoma Screening technics for cervical cancer include 6 – The natural history of cervical cancer represents a stepwise ? Conventional exfoliative cervicovaginal cytology i.e. the progression from a histologically normal cervix to frank cervical (Pap) smear invasive cancer 3 (Figure 1). ? Fluid sampling technics with automated thin layer preparation (liquid based cytology) Why is screening for cervical cancer effective? ? Automated cervical screening technics An ideal screening test is one that is minimally invasive, ? Neuromedical systems easy to perform, acceptable to the subject, cost-effective and efficacious in diagnosing the disease process in its ? HPV testing preinvasive or early invasive state when the disease ? Polar probe process is more easily treatable and curable. ? Laser induced fluorescence ? Visual inspection of cervix after applying Lugol’s iodine In all probability cervical cancer is the only gynecological (VILI) or acetic acid (VIA). cancer that satisfies the well recognized WHO criteria for implementation of a screening program – ? Speculoscopy ? Cervicography. ? Existence of well defined premalignant lesions Exfoliative cytology (conventional Pap smear) ? Long latent period in which premalignant change or occult cancers can be detected and effectively treated Exfoliative cervicovaginal cytology has been regarded as the thereby altering the natural history of the disease gold standard for cervical cancer screening programs. Despite ? A clearly defined viral etiology which could be the apparent success of the Pap smear in detecting preinvasive incorporated as a marker in mass screening program cancer, the expected beneficial impact vis-à-vis mortality 7 ? Easy and direct access of the uterine cervix for reduction has not been significant . The standard technic examination and sampling for Pap smear collection is to sample the portio vaginalis of the cervix and the endocervical canal using a cervical spatula ? Effective treatments available for the premalignant changes. and endocervical brush. The collected sample is smeared on a slide and then fixed immediately with cytology fixative. Most clinicians are concerned with reducing sampling errors Screening for cervical carcinoma by focusing on the technic of smear acquisition and eliminating Screening programs for cervical cancer have been instituted drying artifacts through rapid fixation. in developed countries for decades and over a period of time have been shown to be effective in reducing the overall There are various problems associated with conventional mortality from this disease. Such programs however can cytology – 8 only be made to work provided the necessary infrastructure ? Incorrect and inadequate sampling in 5-10% of cases and funds are available 4. ? Only upto 20% of harvested cells are transferred on the slide leading to a reduction in the sensitivity of the test 8 Following its introduction by Papanicolau in 1927 5 exfoliative 9 cervicovaginal cytology has been extensively investigated and ? Mean sensitivity of only 55-60% 10 used as a screening test for cervical cancer. Over the years ? Reported false negative rates varying from 25 to 50% 11 it has been found that this test has well recognised ? Reported false positive rates varying from 15 to 20 % limitations. A better understanding of the natural history of ? Interobserver variation in the interpretation of cytological cervical cancer as also increasing evidence for the putative abnormality making reporting subjective and poorly role of the human papilloma virus (HPV) in its causation has reproducible 12 now prompted investigators to find viable alternatives to conventional exfoliative cytology. ? Equivocal smears and mildly irregular Pap results have a 116 Review Article low yield of underlying high grade pathology and represent sensitivity of the screening test was also found to be increased a significant cost in terms of specialist referral and follow with ThinPrep. up 7 It is now generally accepted that the improvement in the ? Epidemiological data suggest that the current method of Pap smear testing is unlikely to prevent more than 60% detection rates with these tests is more marked in centers of the cases of cervical cancer 13. with a low risk population as compared to those catering to high risk populations (65% improvement as against 6%). Owing to these problems, several technics have been recently developed in an attempt to automate the various steps of Pap Hartmann et al 18 performed an extensive review of sampling smear preparation and processing in order to try and improve technics and found that most studies of the thin layer technics the sensitivity and specificity of conventional cervical did not have a proper control group thus hindering the ability cytology. to assess the true sensitivity, specificity and predictive value of the technics. They concluded that the current evidence is Fluid sampling technics with automated thin layer not adequate enough to recommend that the ThinPrep test is preparation superior to conventional Pap smear testing. They also Recently liquid based cytological technologies have been suggested that the cost-effectiveness of these tests needs to developed and have gained popularity because in preliminary be assessed very carefully as these tests appear to have a studies the use of such technics was associated with a lower specificity than conventional Pap smear testing, thus reduction in the incidence of inadequate cervical smears 14,15. leading to more specialist referrals. Two such technics that have been extensively tested are Automated screening technology ThinPrep (Cytyc Corp, Booxborough, MA) and Autocyte (TriPath Imaging, Burlington, NC). These fluid sampling The effectiveness of any cervical cancer screening program that relies on cervical cytology is the quality devices have been approved by the USFDA. control of the cytological review of Pap smears. This is A special sampling device is used for sampling the cervix in essential for reducing the false positives and false the usual manner as in the traditional Pap smear. The sampling negatives that invariably result from inter- and intra- device is then directly placed in a vial containing a special observer variation. preservative with additional hemolytic and mucolytic agents. The general idea is to provide a well preserved sample that is Automated screening technics have recently been automatically transferred to a slide as a coin sized thin layer. developed that can not only perform this quality control rescreening but also can be used for primary screening In the laboratory, the cells are collected either by extraction of cervical smears. across a special filter (ThinPrep) or by layering onto a density reagent. The following automated screening technics that rely largely on neural network technology and are based on the Comparisons of the conventional Pap smear with thin layer fluid preparations have shown a marked improvement in the computerized imaging and identification of abnormal cervical adequacy of the specimen as evidenced by a more even cells are available – distribution of cells, and reduction in cellular debris and RBCs. ? Autopap300 (TriPath Imaging, Burlington NC) This in turn leads to a decrease in the incidence of false ? PAPNET (Neuromedical systems). positive diagnosis of cytological atypia and an excellent correlation with the detection of squamous abnormalities. Of these, only the Autopap300 is approved by the USFDA for primary
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