Rajiv Gandhi University of Health Sciences s179
6.1 Need for the study
Since cytology is the examination utilized for the screening of cervical cancer, it is important to determine its correlation with histologic examination, the gold standard in the diagnosis of cervical disease.1
It is well established that cancer of cervix has precursor stages in which there is still no invasion of the stroma. In these stages, we can observe cellular alterations in the cervix which compromise the epithelium of the region and translate into cervical intraepithelial neoplasia(CIN), divided into grades I,II and III(carcinoma in situ). The introduction of colposcopy by Hinslemann in the 1920s and of cervical cytology by Papanicolaou in the 1940s, together with histologic examination by means of a biopsy of the cervix, brought about the basis for the diagnosis of cervical disease.. This type of disease is curable when diagnosed and treated in early stages, as there is a potential for effective prevention of cervical cancer by screening.1
The review of cytology and histology slides is an interesting approach to diminish the possibility of errors in interpretation. The Bethesda system for reporting cervical cytological diagnosis is a uniform system for reporting and it is useful to provide effective communication among cytopathologists and referring physicians. 2
Cytology offers certain advantages over histology in the assessment of cervical dysplasia. Cytology provides exquisite nuclear detail, making early nuclear abnormalities easier to appreciate. Also, the morphology of an intact cell in a cytologic preparation, in comparison to that of the sectioned cell in histology, can be of great help in interpreting subtle abnormalities which may be present in histologic preparations. Finally, a broad area is sampled by a good Pap smear collection, where only a portion of the squamocolumnar junction may be sampled by biopsy2.
The present study is taken to assess the reliability of cervical smears in diagnosing various pathologies of cervix in correlation with histopathological examination.
6.2 Review of the literature
Carcinoma uterine cervix is one of the leading causes of cancer death among women worldwide. To detect this widely prevalent cancer at an early stage, the simplest test has been a pap smear introduced by George Papanicolaou. Reporting of Pap smears is done by using The Bethesda System 2001(TBS) as squamous intraepithelial lesions (SIL) of high and low grades, prior to which many classification systems were developed. To check the sensitivity and specificity of Bethesda System, the cytological findings have to be correlated with histology considering histopathology as gold standard. Several sexually transmitted viruses were considered as possible agents involved in the genesis of cancer of the uterine cervix. The two most important agents are Herpes virus type 2 and Human papillomavirus (HPV).3,4
The earliest details of cervical cytology and biopsy were described in 19th century. During this period biopsy of the cervix was used as a diagnostic tool. The biopsy was undertaken to establish the nature of the lesion. It was soon realized that by this method only advanced disease could be detected. So the search began for new diagnostic methods which would diagnose cervical lesions in early stages. Rubin in 1910 described the structural changes in the epithelium at the periphery of invasive cancer which was considered as a manifestation of early cervical cancer.7
The Bethesda System (TBS) for reporting cervical cytological findings was introduced in 1988 and revised in1991 to establish uniform terminology and standardize diagnostic reports. TBS 2001 was developed through a process that involved committee review of the literature, solicitation of expert opinions and discussion of the proposed changes. Due to easy availability, cost effectiveness and reliability cervical smears became a valuable tool in screening and diagnosing various pathologies of the cervix even at peripheral level in rural place.7
In previous versions of TBS, infections and reactive cellular changes were reported under the categorical heading of “Benign Cellular Changes” (BCC); but under the General categorization section, BCC was separate from “Within Normal Limits” (WNL). To emphasize the ‘negative’ nature of an interpretation of reactive changes, the 2001 Bethesda System collapses the BCC and WNL categories into a single category: “Negative for Intraepithelial Lesion or Malignancy” (NILM). This term is used both as the general categorization and/ or as the interpretation in the report.5
In the study by Gupta and Sodhani analysis of smear characteristics in discrepant cases cervical smears of 100 histology proven cases of Cervical Intraepithelial neoplasia (CIN) III were retrieved and reviewed to study cytohistological agreement in high grade lesions. Cytology was able to correctly identify 74 High grade Squamous Intraepithelial lesions (HSILs) whereas in 26 cases a diagnosis of Low grade Squamous Intraepithelial Lesion (LSIL) or below was given. 16 of these cases were reclassified as HSIL on cytology while 10 cases showed persistent diagnosis of LSIL.6
Bhatla N et al studied pattern of cervical smear cytology and concluded that cervical smear was able to differentiate inflammatory, benign, precursors and malignant cases except in epithelial cell abnormalities, particularly HSIL, where it is advisable to have biopsy. Cervical smear cytology has important role in screening different type of cervical lesions.7
Anschau and Goncalves studied discordance between cytology and biopsy histology of the cervix. They found that out of 255 patients, 42 cases were with normal cytology and histology with HSIL or LSIL. 29 cases with cytology HSIL or LSIL, but with normal histology. 48 cases with cytology LSIL and histology with HSIL. 11 cases with cytology HSIL and histology with LSIL.1
Remzi A et al studied the histopathological correlation of squamous cell abnormalities detected on cervical cytology. They found that increased degree of neoplasia in cervical lesions increases the correlation between pap smear and biopsy.8
Jain V and Vyas AS studied cervical neoplasia –cyto-histological correlation (Bethesda System) for total 276 cases. They found that Pap smear has good sensitivity and specificity and positive predictive value in detecting high grade lesions and malignancy. The sensitivity for cervical intraepithelial neoplasia is low but it can be increased by adequate sampling and avoiding technical errors like air drying and fixation artifacts .3
Bal MS et al studied detection of abnormal smear cytology in Pap smears for 300 cases. They found that mean age of patients with LSIL was 32.3 years and those with HSIL and invasive carcinomas was 40.5 years and 57 years respectively.9
6.3 Objectives of the study
1) To study usefulness of cytology in detecting various cervical lesions.
2) To evaluate and interpret the cases of epithelial lesions according to The Bethesda 2001 classification System.
3) To correlate cytological findings with histology sections.
4) To evaluate the data obtained with appropriate statistical tests.
7. / MATERIALS AND METHODS
7.1 Source of data
Pap smears and cervical biopsies including hysterectomy specimens received in the Department of Pathology at K.V.G. Medical College and Hospital, Sullia.
Study period will be October 2012 to September 2014.
Sample size: Intended to study 100 cases
7.2 Method of collection of data
Cervical smear will be obtained and stained by Papanicolaou technique. It will be examined under microscope and findings will be noted using The Bethesda System. Biopsy –colposcopic guided/ non guided punch biopsy/ Total hysterectomy done at the discretion of gynaecologist will be received. The biopsy specimens will be processed and stained by Haemotoxylin and Eosin stain, followed by microscopic examination.
Appropriate statistical tests are applied as and when required.
Inclusion criteria
i.Women in the reproductive age group of 15 to 45 years.
ii. Women having cervical lesions clinically.
Exclusion criteria
i.Women above 45 years of age.
ii. Women who have undergone previous total hysterectomy.
iii. Women on treatment with radiotherapy and chemotherapy.
Follow up
Nil.
Follow up period
Nil.
7.3 Does the study require any investigation\intervention to be conducted on patients\ humans\ animals? If so, please describe briefly:
in the form of:
i. Smears of uterine cervix.
ii. Biopsy of uterine cervix. Done by the gynaecologists.
7.4 Has ethical clearance been obtained from your institution in case of 7.3?
Yes.
Copy of Ethical Committee Clearance attached.
8. / REFERENCES
1) Anschau F, Goncalves MAG, Discordance between cytology and biopsy histology of the cervix: What to consider and what to do. Acta Cytol, 2011; 55:158-162.
2) Martinez F and Detar MW. Comparing Pap test results with follow-up cervical biopsy findings (Histo-Cyto Correlation).[cited 2012 May 21]. Available from: URL http://incytepathology.wordpress.com/links/ (accessed on 13 October 2012).
3) Jain V, Vyas AS, Cervical neoplasia-Cyto-Histological correlation (Bethesda system) A study of 276 cases. J Cytol Histol, 2010; 1:106.
4) Koss L G and Melamed M R. Squamous carcinoma of uterine cervix and its precursors. In: Koss’ Diagnostic Cytology and its Histopathological basis. Vol 1, 5th edition. Philadelphia: Lippincott Williams and Wilkins, 2006; p283-286.
5) Solomon D and Nayar R editors. Non neoplastic findings. In: Young N A, Bibbo M, Buckner S B, Colgan T J and Prey M U. The Bethesda System for reporting cervical cytology. 2nd edition Springer, 2004; p21-22.
6) Gupta S, Sodhani P. Why is high grade squamous intraepithelial neoplasia under-
diagnosed on cytology in a quarter of cases? Analysis of discrepant cases. Indian
J Cancer, 2004; 41:104-108.
7) Bhatla N, Mukhopadhyay A, Kriplani A, Pandey RM, Gravitt PE, Shah KV et al. Evaluation of adjunctive tests for cervical cancer screening in low resource settings. Indian J Cancer, 2007; 44(2):51-55.
8) Abali R, Bacanakgil BH, Celik S, Aras O, Koca p, Boran Bet al. Histopathological correlation of squamous cell abnormalities detected on cervical cytology .Turk patology Dergisi , 2011;vol.27:144-148.
9) Bal MS, Goyal R, Suri AK and Mohi MK. Detection of abnormal cervical cytology in Pap smears. J.Cytol, 2012; 29(1):45-47.
10) Yeoh GPS, Chan KW. The accuracy of Papanicolaou smear predictions:
cytohistological correlation of 283 cases. HKMJ, 1997; 3:373-376.