|Year : 2016 | Volume
| Issue : 1 | Page : 74-76
Pap test accuracy and severity of squamous intraepithelial lesion
RNO Cobucci, MJAS Maisonnette, EJS Macêdo, FC Santos Filho, PEF Rodovalho, MM Nóbrega, AKS Gonçalves
Department of Gynecology and Obstetrics, Universidade Potiguar–UnP, Natal, Brazil
|Date of Web Publication||28-Apr-2016|
Department of Gynecology and Obstetrics, Universidade Potiguar–UnP, Natal
Source of Support: None, Conflict of Interest: None
Background: Cytology smears and guided biopsies are the most widely used diagnostic standards for cervical cancer (CC) screening in the developing countries. Aim: To evaluate the performance of conventional cytology in estimating the presence and grade of cervical disease against the reference standard of histopathology. Settings and Design: After primary screening for CC, directed biopsies were performed and compared with histopathology results. Materials and Methods: Papanicolaou (Pap) smears and biopsies from 3194 women in the age group of 14-98 years were included. Cytology results were provided by doctors who performed the cervical biopsies. Statistical Analysis: The accuracy of Pap smear was measured by sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) calculated using the statistical analysis program PSPP 0.7.8. Results: The sensitivity of conventional cytology (Pap smear) for women with low-grade cervical intraepithelial neoplasia or less serious lesions (CIN1-) was 93% and specificity was 73%. The sensitivity and specificity of cytology for women with high-grade cervical intraepithelial neoplasia or cancer (CIN2+) was 64% and 84%, respectively. Conclusion: Cytology is a sufficiently sensitive test for detection of cervical lesions and can be used as a primary testing tool to triage.
Keywords: Cancer, cytology, uterine cervical diseases
|How to cite this article:|
Cobucci R, Maisonnette M, Macêdo E, Santos Filho F C, Rodovalho P, Nóbrega M M, Gonçalves A. Pap test accuracy and severity of squamous intraepithelial lesion. Indian J Cancer 2016;53:74-6
|How to cite this URL:|
Cobucci R, Maisonnette M, Macêdo E, Santos Filho F C, Rodovalho P, Nóbrega M M, Gonçalves A. Pap test accuracy and severity of squamous intraepithelial lesion. Indian J Cancer [serial online] 2016 [cited 2020 Jun 6];53:74-6. Available from: http://www.indianjcancer.com/text.asp?2016/53/1/74/180825
| » Introduction|| |
Cervical cancer (CC) is still a health problem in countries where CC screening is not routinely performed; despite this, CC remains the only human malignancy to have been successfully reduced by medical intervention.
CC screening using conventional cytology has been conducted worldwide to reduce the incidence and mortality of this disease. Despite being the most widely used, Papanicolaou (Pap) smear has presented several limitations, which result from the number of consecutive compulsory steps required to reach a satisfactory outcome. Imperfect sensitivity as well as errors in sample collection and professional interpretation are grounds for frequent repeated screening. To address these issues, researchers have begun to look for greater accuracy in technological advances, such as using liquid-based cytology (LBC) and high-risk human papillomavirus (HPV) tests.,
In recent years, high-risk HPV testing has been incorporated into screening triage algorithms by the American Society for Colposcopy and Cervical Pathology (ASCCP), as well as in post-colposcopy and post-treatment surveillance. Several studies evaluating double testing accuracy ( Pap smear More Details and HPV testing) showed that HPV testing has greater sensitivity but lower specificity in detecting high-grade cervical intraepithelial neoplasia (CIN) compared with cytology.,,
Over several years, numerous debates have taken place in attempts to identify the optimal method of internal quality control for cervical cytology. The scientific community agrees that the most rigorous method to avoid screening errors and consequently monitoring the quality of routine Pap smears in laboratories is repeat scrutiny of all routine tests defined as negative. Re-assessment of negative smears is the most common approach used to detect false-negative results. The methods used include retrospective review, review of cases based on clinical risk criteria, and a 10% random review of negative results. Other methods entail rapid screening techniques, or rapid review of all negative smears, and, more recently, rapid pre-screening of all smears.
The ideal screening strategy should identify those CC precursors likely to progress to invasive cancers, thus maximizing the benefits of screening. It should also avoid the detection and unnecessary treatment of transient HPV infection, and its associated benign lesions not destined to become cancerous, consequently minimizing the potential harm associated with screening.
Comparison of cytology with histology results allows us to evaluate diagnostic capabilities and reflect on clinical usefulness in detecting cancer of the cervix early. This study aims to evaluate the accuracy of cytology in detecting precancerous lesions and CC.
| » Materials and Methods|| |
This cross-sectional study was conducted at the Pathology Laboratory from January to December 2011. We included all biopsies performed during the study period, totaling 3194 histopathological results. Patient age and Pap smear results were obtained from biopsy patient information forms sent to the laboratory. The Bethesda System 2001 was the nomenclature used for exam classification.
Negative cytology was defined as inflammatory changes and squamous metaplasia, whereas positive cytology was defined as atypical cells in the squamous or glandular epithelium and more severe lesions.
The Bethesda System classifies lesions in the squamous epithelium as atypical squamous cells of undetermined significance (ASC-US), which are probably not neoplastic, and atypical squamous cells of undetermined significance, which cannot exclude the diagnosis of high-grade lesion (ASCH), low-grade intraepithelial lesions (LSIL), high-grade intraepithelial lesions (HSIL), as well as invasive carcinoma (CA). In glandular epithelium lesions are classified as: Atypical glandular cells (AGC) and adenocarcinoma.
The product of the biopsy was routinely prepared (hematoxylin/eosin) and submitted to a histopathological examination. Histopathology results were classified into five categories of increasing disease severity: Normal/no neoplastic abnormalities, CIN, identified at varying levels of severity (CIN1, CIN2, CIN3), and CA.
The study outcome was defined as CIN1 and less serious lesions (CIN1-) or CIN2 and more serious lesions (CIN2+), and this disease threshold was used to calculate sensitivity, specificity, and predictive values of the screening tests. The final reference diagnosis was based on the histopathology findings. The statistical analysis program used was PSPP 0.7.8.
This research project was approved by the Ethics Committee on Human Research. All involved patients were properly informed concerning the aims of the study and were included only after they agreed to participate and sign an informed consent form (no. 047/047/2011).
| » Results|| |
The women included in this study were between the ages of 14 and 98, with an average of 34.9 years (SD ± 10.1). The average age of the women with negative Pap smears, ASC-US, ASCH, AGC, LSIL, HSIL, and CA were 33.4, 34.6, 37.3, 36.6, 38.1, and 56.8 years, respectively [Table 1].
The cytology results were described as negative in 18% (n = 574) of the cases. Positive results (n = 2620) were as follows: ASC-US 11.8% (n = 378), ASCH 0.3% (n = 8), AGC 0.4% (n = 14), LSIL 55.9% (n = 1786), HSIL 13.1% (n = 418), and CA 0.5% (n = 16) [Table 1].
Within the 3194 histopathological exams analyzed, 24.4% (n = 778) were found to be negative. Positive results were found in 75.6% (n = 2416), where 62% (n = 1981) were determined as CIN1, 13.2% (n = 422) as CIN2 or CIN3, and 0.4% (n = 13) as CA [Table 1].
The histopathological examination confirmed negative results in 176 women of the 574 cases found negative by cytology and positive results in 2018 of the 2620 cases found to have ASC-US+ cytology; accuracy was found to be 77%, sensitivity 83%, specificity 23%, PPV 77%, and NPV 30% [Table 2].
When comparing conventional cytology (LSIL and atypical changes) with the gold standard of histopathology (CIN1-), sensitivity was found to be 93%, specificity 73%, PPV 90%, and NPV 73% [Table 3].
Similarly, when comparing conventional cytology (HSIL and CA) with the gold standard of histopathology (CIN2+), sensitivity, specificity, PPV, and NPV were 64%, 84%, and 99%, respectively [Table 3].
| » Discussion|| |
The efficiency and effectivity of the Pap smear depends on how engaged the women are in the cancer screening programs, adequate sample collection, and the quality of laboratory analysis. Insufficient or inadequate samples are responsible for approximately two-thirds of all false-negative results. In this study, 9.4% (132/1432) of the Pap smears were false negatives. Of these women found to have normal cytology, histopathological examination revealed CIN1 in 127 and CIN2+ in 5. Some studies report that false negatives occur in 1% to 20% of the examinations, with an average of between 1% and 5%.
Pimple et al. observed the main cause of cytological false negatives in HSIL patients to be air-drying artifact as well as immature squamous metaplasia. Improper interpretation of laboratory slides is the most probable explanation outside greater city areas in underdeveloped countries. In our study, cytology produced good results for both CIN2+ (sensitivity 64%, specificity 84%) and CIN1- (sensitivity 93%, specificity 73%) groups; however, again, such results require good laboratory services and skilled cytologists, both found in the pathology service of our university. In a recent meta-analysis, Chen et al. supported some of these findings by reporting a sensitivity of 59% and a specificity of 94%. However, Nanda et al. found a much greater variation in sensitivity and specificity, with a range from 30-87% and 86-100%, respectively. The discrepancy in the literature is most probably caused by the aforementioned factors. The lowest specificity for CIN1 in this study can be explained by the fact that some cytological changes suggestive of LSIL, which are caused by other microorganisms such as fungus and bacteria, easily confound examiner interpretation. This results in an increased rate of false-negative cytology results.
In similar studies, which compare cytology to histology, sensitivity ranged from 23.5 to 76%, specificity from 63.2% to 99, 4%, PPV from 42% to 100%, and NPV from 43.7% to 96%. Higher specificity values were consistently found related to CIN2+, thus supporting our study.,,,,,,,,,
Several studies reported a progressive increase in the severity of the lesion with advancing age. LSIL is found to peak between 20 and 29 years, HSIL between 30 and 39 years, and CA between 50 and 59 years of age.,, Comparably, in our study, the mean age of patients with LSIL was 34.4 years, and those with HSIL and CA were 38.1 and 56.8 years, respectively.
Our research found epithelial cell abnormalities in 82% of the smears. Prevalence of ASC-US was 11.8% (378 cases). Squamous intraepithelial lesions were seen in 69% of the cases (2204), out of which LSIL was in 55.9% (1786) and HSIL accounted for 13.1%. CA was seen in 0.5% of the cases. These results are not comparable to those obtained by the few studies, which have documented low prevalence of LSIL and HSIL.,, The probable cause for this is that our sample originated from a university laboratory where women were referred for cancer and precursor lesion screening, thus concentrating more women with abnormal cytology than present in the general population.
Cervical cytology by Pap smear is a simple, safe, and cost-effective test to detect premalignant and malignant cervical lesions at an early stage, thus facilitating early diagnosis and efficient patient treatment. Although cytology is suggested as a screening method, new proposals such as visual inspection of the cervix are being evaluated, especially in developing countries where CA has a high prevalence of morbidity and mortality. The association of this method with conventional cytology in CA screening has been shown favorable since it has increased sensitivity to 82.6% and specificity to 92.2% in recent studies.,
Despite the development of new technologies to diagnose CC such as molecular biology methods (polymerase chain reaction (PCR) and hybridization), Pap smear still remains the most useful and efficient. Cytology should be encouraged as a screening method in developing countries due to its low cost and effectiveness in detecting cervical lesions, especially high-grade. However, its limitations must be recognized and its association with other cost-effective methods such as visual inspection with acetic acid can be a powerful tool to improve screening of CA and precursor lesions, consequently reducing morbidity and mortality.
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[Table 1], [Table 2], [Table 3]
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