|Year : 2013 | Volume
| Issue : 4 | Page : 292-296
The importance of immediate verification of a cervical cytological abnormality with histology
C Kabaca1, B Sariibrahim2, I Keleli2, A Karateke1, S Cesur3, H Cetiner3
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 Publication||24-Dec-2013|
Department of Gynecologic Oncology, Zeynep Kamil Women and Children Diseases Education and Research Hospital, Istanbul
Source of Support: None, Conflict of Interest: None
Clinical trial registration İJC_136_12
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 Jun 2];50:292-6. Available from: http://www.indianjcancer.com/text.asp?2013/50/4/292/123591
| » Introduction|| |
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.  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. , Inadequate management of cytologic abnormality is blamed in 4-13% of patients with invasive cervical cancer.  Although there is a real consensus in the management of high grade cytological abnormalities,  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.  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. 
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|| |
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.  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|| |
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|| |
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.  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.  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.  Prevalence of invasive cancer is low in women with ASC (approximately 0.1%-0.2%).  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.  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.  The prevalence of CIN 2-3 or cancer among women ASC-H ranges from 26-68%.  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%. , 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.,  suggested that cervical biopsy had been more effective than cytologic follow-up in women with low grade squamous abnormalities. Souther and Fletcher  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. , 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.  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. ,, 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. , 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.  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.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]
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