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ORIGINAL ARTICLE
Year : 2013  |  Volume : 50  |  Issue : 4  |  Page : 292-296
 

The importance of immediate verification of a cervical cytological abnormality with histology


1 Department of Gynecologic Oncology, Zeynep Kamil Women and Children Diseases Education and Research Hospital, Istanbul, Turkey
2 Department of Obstetrics and Gynecology, Zeynep Kamil Women and Children Diseases Education and Research Hospital, Istanbul, Turkey
3 Department of Pathology, Zeynep Kamil Women and Children Diseases Education and Research Hospital, Istanbul, Turkey

Date of Web Publication24-Dec-2013

Correspondence Address:
C Kabaca
Department of Gynecologic Oncology, Zeynep Kamil Women and Children Diseases Education and Research Hospital, Istanbul
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.123591

Clinical trial registration İJC_136_12

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 » Abstract 

Background: A serious proportion of the patients with invasive cervical cancer can be women who have had abnormal smear findings known for at least 6 months. Aims: The aims of the study were to evaluate the cervical cytohistopathologic correlation in the population studied, and to discuss the acceptability of immediate histological verification for minor Papanicolaou smear abnormalities. Materials and Methods: A total of 443 patients who were admitted with abnormal smear results and had undergone immediate colposcopy, cervical biopsy and endocervical curretage in the gynecologic oncology clinic between the years of 2003-2009 were enrolled into the present retrospective study. One-way analysis of variance and independent t-tests were used to study the results. Results: The distribution of abnormal smear results were documented as 46.27%, 29.57%, 13.76%, 7.67%, 1.58%, 0.67%, and 0.45% for atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H), squamous cell carcinoma (SCC), atypical glandular cell (AGC), and adenocarcinoma, respectively. The percentages of cervical intraepithelial neoplasia grade 2-3 (CIN 2-3) and greater lesions were 70.49%, 35.29%, 15.26%, and 9.75% for HSIL, ASC-H, LSIL, and ASC-US, respectively. Moreover, 38.36% of all the CIN 2-3 or cancer (n = 104) cases originated from those with low grade referral diagnosis (ASC-US and LSIL). Conclusions: The majority of cases in the study were predominantly ASC-US and LSIL and approximately 40% of all the high grade lesions came from those with low grade referral diagnosis. This shows poor cytohistopathological correlation and calls the triage of minor cytological abnormalities into question.


Keywords: Atypical squamous cells of undetermined significance, biopsy, colposcopy, cytohistopathological correlation, papanicolaou smear


How to cite this article:
Kabaca C, Sariibrahim B, Keleli I, Karateke A, Cesur S, Cetiner H. The importance of immediate verification of a cervical cytological abnormality with histology. Indian J Cancer 2013;50:292-6

How to cite this URL:
Kabaca C, Sariibrahim B, Keleli I, Karateke A, Cesur S, Cetiner H. The importance of immediate verification of a cervical cytological abnormality with histology. Indian J Cancer [serial online] 2013 [cited 2020 Oct 22];50:292-6. Available from: https://www.indianjcancer.com/text.asp?2013/50/4/292/123591



 » Introduction Top


The goal of cervical cancer screening by cytology using Papanicolaou (Pap) testing is to detect and remove the precursor lesions of cervical cancer and thereby decrease the incidence of cervical cancer. [1] A serious proportion (36-70%) of the previously screened women with invasive cervical cancer are reported to have had abnormal smear findings more than 6 months prior to cancer diagnosis. [2],[3] Inadequate management of cytologic abnormality is blamed in 4-13% of patients with invasive cervical cancer. [2] Although there is a real consensus in the management of high grade cytological abnormalities, [4] debates are still going on about the correct and adequate way of management [such as 2-repeat cytologic examinations, colposcopy and biopsy, human papilloma virus (HPV) test] in low grade cytological abnormalities. [5] Many additive burdens influencing patients, physicians and payors such as the psychological and physical morbidity of colposcopy and biopsy, the risk of overloading of colposcopy clinics, and high costs have been arguments in favor of cytologic follow-up. On the contrary, concerns about the risk of drop out from cytologic follow-up, increased risk of any omitted invasive cancer or high grade lesion already existing, as well as increased anxiety during cytologic follow-up, have favored a counter policy which encourages colposcopy and biopsy. [6]

The aim of this study was to evaluate how the abnormal  Pap smear More Details findings correlated with the risk of invasive cervical cancer or high-grade cervical intraepithelial neoplasia (CIN) which already exist. The other aims were to evaluate the rationale of immediate verification of the minor cytologic abnormality with histology, and to discuss the additive effect of routine endocervical curettage (ECC) in detecting additional cases of high grade dysplasia.


 » Materials and Methods Top


The patients who were admitted with abnormal Pap smear results and who underwent immediate colposcopy, cervical biopsy and ECC in the gynecologic oncology clinic in the Zeynep Kamil Women and Children Diseases Education and Research Hospital between the years of 2003-2009 were enrolled into the presented retrospective study. The patients' data were collected by chart review. The study has been reviewed by the local ethics committee. Cytology results were reported either by the pathology department of our hospital or came from external centers. The reasons like possibility of dropping out from cytological follow-up, the financial status of payors leading to refusal of expensive tests such as for human papilloma virus (HPV), and the absence of mandatory rules about cervical cancer screening in our country have encouraged us to prefer immediate colposcopy, cervical biopsy and ECC for all patients with abnormal Pap smear. All histopathological specimens were examined in the pathology department of our hospital.

The 2001 Bethesda system terminology was used for cytologic classification. [7] All biopsies were taken with a cervical punch biopsy tool. Cervical biopsies were taken from colposcopic abnormal areas or randomly from four cervical quadrants if there was no obvious abnormality or in cases of inadequate colposcopic results. Routine ECC was performed on all patients. The histologic diagnosis was deemed as normal (absence of atypia), CIN grade 1(CIN 1), CIN grade 2 (CIN2), CIN grade 3 (CIN3), squamous cell carcinoma (SCC), and adenocarcinoma. When more than 1 cytologic or histologic diagnosis had been reported, the most severe one was considered as the main diagnosis. Patients with a previous history of cervical, vaginal, or vulvar carcinoma were not included in the study. Statistical analyses were performed with Statistical Package for Social Sciences (SPSS) version 11.0 (SPSS, Chicago, IL, USA) by using descriptive statistical methods. The data was statisticaly analyzed using one-way analysis of variance (ANOVA) and independent t test. P < 0.05 indicated statistical significance.


 » Results Top


A total of 443 patients with abnormal Pap smear results underwent colposcopic examination, cervical biopsy and ECC in our gynecologic oncology clinic. The mean age of patients was 40.02 ± 9.92 years. When the mean ages of the patients with abnormal cytology types were examined, the patients with SCC and adenocarcinoma were found to be older than others (P < 0.0001, one-way ANOVA) [Table 1]. The distributions of abnormal smear results were documented as 46.27%, 29.57%, 13.76%, 7.67%, 1.58%, 0.67%, and 0.45% for atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), atypical squamous cells which cannot exclude HSIL (ASC-H), SCC, atypical glandular cell (AGC), and adenocarcinoma, respectively. The biopsy and ECC results of all patients with abnormal smear results were normal in 55.53% of the cases.
Table 1: Distribution of the mean ages of the patients according to abnormal cytology result in the study

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CIN1, CIN 2-3, SCC, adenocarcinoma, and malignant melanoma were encountered in 20.99%, 17.38%, 4.96%, 0.9% and 0.2% of the patients, respectively. The histological counterparts of the abnormal cytology results are listed in [Table 2]. According to these results, all patients with Pap smear indicating invasive cancer had invasive cancer confirmed histologically. Moreover; invasive cancer was detected in 11.47% of patients with HSIL, in 17.64% of patients with ASC-H, in 1.95% of patients with ASC-US and in 0.76% of patients with LSIL. The detection rates of all cases with CIN 2-3 or cancer were 70.49%, 35.29%, 15.26%, and 9.75% for HSIL, ASC-H, LSIL, and ASC-US, respectively. There were no statistical differences between the mean ages of the patients with and without CIN2-3 or greater lesion in the groups with LSIL (37.1 ± 11.72 vs. 38.44 ± 9.6 years), as well as with ASC-US (42.94 ± 12.39 vs. 39.7 ± 1.12 years) (P > 0.05 for both groups, independent t test).
Table 2: The histologic counterparts of the abnormal cytology results in the study

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The 75.84% of the cases in the study were ASC-US and LSIL. The 38.46% (n = 40) of all the CIN2-3 or cancer (n = 104) cases were diagnosed in the groups with either ASCUS or LSIL.

Additional CIN lesions located solely within the endocervical canal were detected in 14 patients by concomitant application of ECC with cervical punch biopsy. In other words, 3.16% (n = 14) of final diagnosis relied on the result of ECC alone. Addition of ECC to cervical punch biopsy resulted in the correct diagnosis of additional CIN 3 cases in 0.48% (n = 1), 0.76% (n = 1), and 8.19% (n = 5) of the patients with ASC-US, LSIL and HSIL, respectively. The images of ASC-US, ASC-H, HSIL smears with their CIN3 histological correlations are shown in [Figure 1], [Figure 2], [Figure 3], respectively.
Figure 1: Atypical squamous cells of undetermined significance smear with its cervical intraepithelial neoplasia grade 3 histological correlation

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Figure 2: Atypical squamous cells cannot exclude high‑grade squamous intraepithelial lesion smear with its cervical intraepithelial neoplasia grade 3 histological correlation

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Figure 3: High‑grade squamous intraepithelial lesion smear with its cervical intraepithelial neoplasia grade 3 histological correlation

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 » Discussion Top


Cervical cancer is the ninth most common cancer among women in the country where the present study has been accomplished, and ranks 12 th among cancer-related deaths. [8] In spite of the success of cytology as a cervical cancer screening method, there are still problems related to cytologic screening such as nonparticipation in screening, dropping out from cytologic follow-up protocol despite cytologic abnormality, or a number of significant limitations related to cytologic diagnosis. [9] The management of cytologic abnormality by methods like cytologic follow-up or a triage may be suitable for high socioeconomic populations with mandatory participation in cervical cancer screening program. In countries with low or non-existent cervical cancer screening programs' participation, any patient who applied to a hospital with any complaint should be managed with a "screen-diagnose-treat" protocol.

In the 2001 Bethesda System, atypical squamous cells (ASC) is subcathegorized into ASC-US and ASC-H. [7] Prevalence of invasive cancer is low in women with ASC (approximately 0.1%-0.2%). [10] However, in our study, these rates were 1.95% for ASC-US and 17.64% for ASC-H. The rate of histologically proven invasive cancer in ASC-US cytology was 10-fold more in our series when compared to the related literature. CIN 2 or greater lesions were detected at enrollment colposcopy in 10.2% of patients with unknown HPV status with ASC-US in ASC-US/LSIL Triage study. [11] In our study, CIN 2 or greater lesions were detected in 9.75% of ASC-US cytologies.

According to the 2006 consensus guidelines, ASC-H should be considered to represent equivalent HSIL. [4] The prevalence of CIN 2-3 or cancer among women ASC-H ranges from 26-68%. [4] The rate of CIN 2-3 or cancer among ASC-H was 35.29% in our study. The rate of invasive cancer in patients with ASC-H was more than the rate in patients with HSIL in the present study (17.64% for ASC-H and 11.47% for HSIL). Although the cancer rate was higher in the ASC-H group when compared to patients with HSIL, pathologic examination reported normal findings in 47% of patients with ASC-H.

The prevalence of CIN 2 or greater lesion identified at initial colposcopy among women with LSIL has been reported to range between 12 and 16%. [12],[13] Our study revealed a similar results with the literature. The rate of CIN 2 or greater lesion was 15.26% for LSIL cytologies. The 75.84% of the cases in the present study were ASC-US and LSIL. The 38.46% (n = 40) of all the CIN 2-3 or cancer (n = 104) cases were diagnosed in the groups with ASC-US and LSIL, namely the groups with low grade referral diagnosis.

Histologic assessment was strongly associated with a decreased risk of invasive cervical cancer compared to cytologic follow-up in women with low grade squamous abnormalities. Silfverdal et al., [6] suggested that cervical biopsy had been more effective than cytologic follow-up in women with low grade squamous abnormalities. Souther and Fletcher [14] showed, in a reanalysis of long term studies, that women with low grade abnormal smear findings who had been surveyed cytologically had had 16-47 times higher incidence of invasive cancer than the general population. The results of a recent metaanalysis of randomized trials showed that compliance with cytologic follow-up declines over time in women with low-grade cytologic abnormalities. [6],[15] These findings support the importance of diagnostic assessment with cervical biopsy at the initial examination.

Approximately 2% of women with HSIL are believed to have concomitant invasive cancer. [16] In the present study, 11.47% of women with HSIL had invasive cancer. A single colposcopic examination identifies CIN 2 or greater lesion in 53.66% of women with HSIL. [13],[17],[18] In our study, CIN 2 or greater lesions were detected in 70.49% of patients with HSIL. These results justify that cytologic follow-up was not an option in patients with HSIL as it has also not been recommended in the guidelines. [4],[6] Since single colposcopic examination can miss significant number (up to 50%) of CIN 2,3 lesions, failure to detect CIN 2,3 at colposcopy in a women with HSIL does not necessarily mean a CIN 2,3 lesion is not present. [11] We performed ECC in addition to cervical biopsy in all patients. Thus, CIN 3 could only be diagnosed by ECC in 8.19% of patients with HSIL. Therefore, ECC must accompany the cervical punch biopsy.

Our findings showed that ASC-US smear results have been accompanying with high grade histological lesions with a rate which cannot be ignored. Additionally, ASC-H smear results must be identically evaluated as HSIL smear results. The evaluation of endocervical canal is important especially in patients with high grade cytologic abnormalities. Immediate verification of the cytologic abnormality with histology instead of triage should be recommended in selected countries where smear screening had not been built on a firm ground yet and where the HPV test has high costs. Besides, immediate verification with histology is necessary when high possibilities of non-attendance and dropping out from cytologic surveillance are predicted.

 
 » References Top

1.Gustafsson L, Ponten J, Zack M, Adami HO. International incidence rates of invasive cervical cancer after introduction of cytological screening. Cancer Causes Control 1997;8:755-63.  Back to cited text no. 1
    
2.Sasieni PD, Cuzick J, Lynch-Farmery E. Estimating the efficacy of screening by auditing smear histories of women with and without cervical cancer: The National Co-ordinating Network for Cervical Screening Working Group. Br J Cancer 1996;73:1001-5.  Back to cited text no. 2
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3.Andersson-Ellstrom A, Seidal T, Grannas M, Hagmar B. The Pap-smear history of women with invasive cervical squamous carcinoma: Acase control study from Sweden. Acta Obstet Gynecol Scand 2000;79:221-6.  Back to cited text no. 3
    
4.Wright TC Jr, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D. American Society for Colposcopy and Cervical Pathology-sponsored Consensus Conference. 2006 Consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol 2007;197:346-55.  Back to cited text no. 4
    
5.Bently E, Cotton SC, Cruickshank ME, Duncan I, Gray NM, Jenkins D, et al. Trial of Management of Borderline and Other Low-Grade Abnormal Smears (TOMBOLA) Group. Refining the management of low-grade cervical abnormalities in the UK National Health Service and defining the potential for human papillomavirus testing: A commentary on emerging evidence. J Low Genit Tract Dis 2006;10:26-38.  Back to cited text no. 5
    
6.Silfverdal L, Kemetli L, Andrae B, Sparen P, Ryd W, Dillner J, et al. Risk of invasive cancer in relation to management of abnormal Pap smear results. Am J Obstet Gynecol 2009;201:188.e1-7.  Back to cited text no. 6
    
7.Solomon D, Davey D, Kurman R, Moriarty A, O′Connor D, Prey M, et al. Forum Group Members; Bethesda 2001 Workshop. The 2001 Bethesda System: Terminology for reporting results of cervical cytology. JAMA 2002;287:2114-9.  Back to cited text no. 7
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8.International Agency for Research on Cancer. Available from: http://www-dep.iarc.fr/globocan/database.htm. [Last accessed on 2012 Mar 20].  Back to cited text no. 8
    
9.Cervix Cancer Screening. IARC Handbooks of Cancer Prevention, Vol. 10. Lyons, France: IARC Press; 2005.  Back to cited text no. 9
    
10.Jones BA, Novis DA. Follow-up of abnormal gynecologic cytology: A college of American pathologist Q-probes study of 16132 cases from 306 labarotories. Arch Pathol Lab Med 2000;124:665-71.  Back to cited text no. 10
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11.ASCUS-LSIL Traige Study (ALTS) Group. Results of a randomized trial on the management of cytology interpretations of atypical squamous cells of undetermined significance. Am J Obstet Gynecol 2003;188:1383-92.  Back to cited text no. 11
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12.Chute DJ, Covell J, Pambuccian SE, Stelow EB. Cytologic-histologic correlation of screening and diagnostic Papanicolaou tests. Diagn Cytopathol 2006;34:503-6.  Back to cited text no. 12
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13.Alvarez RD, Wright TC, Optical Detection Group. Effective cervical neoplasia detection with a novel optical detection system: A randomized trial. Gynecol Oncol 2007;104:281-9.  Back to cited text no. 13
    
14.Soutter WP, Fletcher A. Invasive cancer of the cervix in women with mild dyskaryosis followed up cytologically. BMJ 1994;308:1421-3.  Back to cited text no. 14
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15.Kyrgiou M, Koliopoulos G, Martin-Hirsch P, Kehoe S, Flannelly G, Mitrou S, et al. Management of minor cervical cytological abnormalities: A systematic review and a meta-analysis of the literature. Cancer Treat Rev 2007;33:514-20.  Back to cited text no. 15
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16.Jones BA, Davey DD. Quality management in gynecologic cytology using interlaboratory comparison. Arch Pathol Lab Med 2000;124:672-81.  Back to cited text no. 16
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17.Massad LS, Collins YC, Meyer PM. Biopsy correlates of abnormal cervical cytology classified using the Bethesda system. Gynecol Oncol 2001;82:516-22.  Back to cited text no. 17
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18.Dunn TS, Burke M, Shwayder J. A "see and treat" management for high-grade squamous intraepithelial lesion pap smears. J Low Genit Tract Dis 2003;7:104-6.  Back to cited text no. 18
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2]

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