PAP SMEAR by Dr.Shantha Krishnamurthy MD Senior Consultant Pathology Fortis Hospitals

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1 PAP SMEAR by Dr.Shantha Krishnamurthy MD Senior Consultant Pathology Fortis Hospitals

2 Historical Named after George Papanicolaou, a Greek American Studied cervical epithelium in menstrual cycle of guinea pigs and later in humans Noted abnormal cells in vaginal smears in normal looking cervices

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4 Pap Test One of the most simple and effective cancer screening tools till date Organised cervical cancer screening programs have brought down the incidence of cervical cancer by 70 % in the US Mostly opportunistic screening carried out in India

5 Organised Screening Programmes Was associated with a population based screening programme conducted by IARC, Lyon,France and funded by Bill and Melinda Gates foundation in collaboration with Tata Memorial Hospital,Mumbai Barshi near Sholapur, Maharashtra-High Prevalence area 30, 000 women in each of four arms VIA, Pap smear, HPV testing and controls Results have been published

6 Problems along the way Bad selection of women,improperly collected or stained smear, screening and interpretation errors and finally inaction or overaction by the clinicians Low detection rates of epithelial abnormalities

7 Cervical Cancer-1 Is a sexually transmitted disease Caused by Human Papilloma Virus HPV Infections are common Not all progress to cancer

8 Cervical cancer -2 Long latent period High risk and low risk types Zur Hausen established the relationship of HPV to cervical cancer Awarded the Nobel Prize for Medicine in 2008

9 Latent Period

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11 Pathogenesis of HPV Infection-1 Infects the basal cells of the epithelium Episomal replication Uses the cell machinery for replication Kills the cell (cytopathic effect )

12 Pathogenesis of HPV infection-2 Infects other cells Eliminated or persists based on the immune status of the host Cancer results from integration of the viral genome into the nucleus.

13 Spectrum of HPV associated Cervical lesions Flat lesions- Flat condylomas and Cervical Intraepithelial Neoplasia grades I,II III Exophytic Condylomatous lesions Squamous Papillomas Cervical Squamous cell and adenocarcinomas

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21 HPV DNA testing At present expensive. Best reserved for: Equivocal smears Low grade smears in older women Post treatment surveillance after treatment for cervical intraepithelial neoplasia With introduction of HPV vaccination in children, some of the practices are likely to change

22 Role of Pap smear Is to identify asymptomatic patients with precancerous lesions of the cervix Other findings such as parasites, fungi are bonuses Not meant for diagnosing symptomatic women with invasive carcinoma for which biopsy is preferable Not suitable for identifying endometrial pathology

23 Precancerous lesion Terminology in histology Cervical intraepithelial neoplasia grades I,II and IIi

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25 2014-Bethesda system of reporting-1 Specimen type- Conventional, LBC or other Specimen adequacy General Categorisation-NFIELM, Other, Epithelial cell abnormality Interpretation Results

26 2014-Bethesda system of reporting-2 Interpretation Results -NFIEL/Malignancy-Non-neoplastic, RCC, Microorganisms -Epithelial cell abnormalities Sq Cell-ASCUS, ASC-H,LSIL,HSIL,SCC Glandular-Atypical, Atypical favor neoplastic and Adenocarcinoma- specify if EC, Endometrial or NOS

27 Squamous Epithelial cell abnormalities ASCUS-Atypical squamous cells of uncertain significance Koilocytotic changes consistent with HPV Infection Low Grade Squamous Intraepithelial Lesion(LSIL) High Grade Intraepithelial Lesion(HSIL) HSIL cannot rule out squamous cell carcinoma.invasive squamous cell carcinoma

28 ASCUS Cells showing 2-3 times the size of intermediate cell nuclei with slight hyperchromasia and no significant chromatin abnormalities or membrane irregularity Usually further qualified as either favoring or not favoring SIL

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30 Koilocyte Means hollow or concave Pathognomonic of HPV infection. Is an intermediate dead cell showing cytopathic effect of HPV infection Large vacuole with irregular cytoplasmic border and enlarged hyperchromatic, smudged raisin like nucleus Dyskeratosis is often seen Koilocyte is not a dysplastic cell because it is a dead cell and is incapable of dividing

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32 LOW GRADE INTRAEPITHELIAL LESION(LSIL) Cellular changes seen in intermediate and superficial cells The nuclei are enlarged and show chromatin abnormalities and membrane irregularities Nuclear changes maybe seen in a cell with cytoplasmic clearing as evidence of virus cytopathic effect (Koilocytotic dysplasia) Koilocytes are usually seen in the background

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34 HIGH GRADE INTRAEPITHELIAL LESION(HSIL) Seen in parabasal cells Raised N/C ratio Hyperchromasia (Pale dyskaryosis) Irregular nuclear membrane thickening Membrane irregularities with grooves Lack nucleoli

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36 SQUAMOUS CELL CARCINOMA Altered cell shapes-fiber cells, tadpole cells etc Marked nuclear pleomorphism Ink dot (pyknotic)nuclei Cookie cutter cell outlines Tumor diathesis Nucleoli seen if viable cells are shed

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38 Glandular cell abnormalities Atypical glandular cells Atypical glandular cells favor neoplastic Adenocarcinoma in situ Invasive Adenocarcinoma Well differentiated adenocarcinoma not easy to diagnose on cytology

39 Invasive Adenocarcinoma

40 Cervical Adenocarcinoma Not as common as squamous cell carcinoma Can show a variety of patterns and cell types Must rule out extension from endometrium by appropriate imaging

41 Future of Pap smear-1 Since rates of detection of cervical abnormalities in pap smear are generally low, the manual screening needs to be replaced With advances in imaging, efforts are on to use fully automated techniques which will compare the images of the smear with data stored in the computer

42 Future of Pap smear-2 This will allow for only the abnormal smears picked up by the computer to be rescreened by the human eye. Only future studies will show the efficacy of such an approach Role of HPV vaccination in prevention of cervical cancer- Pap Test maybe done away with?

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44 Male Factor Being an STD, it stands to reason that the male factor be also taken into account HPV implicated in cancers at other sites e.g oral, anal, urinary tract, skin etc HPV vaccine why only for females?

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