premalignant and malignant disordes of cervix 28-5-2019.pptx

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1. BY DR ANJUM MAHMOOD PREMALIGNANT AND MALIGNANT DISEASES OF CERVIX

2. LEARNING OBJECTIVES To be able to understand that CIN is a premalignant condition To know that it is treatable To have the knowledge about cervical screening and its importance To be able to know about different screening modalities To know that HPV vaccines are protective against cervical cancer To know that effective screening has reduced the incidence of cervical cancer significantly in developed countries

3. ANATOMY OF CERVIX The cervix represents the lower cylindrical distal portion of the uterus and is divided into: Ectocervix Endocervix The portion of the cervix projecting into the vagina is called portiovaginalis (3cm length) The ectocervix --- portiovaginalis is visible during a speculum examination The cervix opens onto the vagina through an orifice called the External os

4. The endocervix ( endocervicalcanal ) is a luminal cavity within the cervix forming a passageway between the external os and the internal os . The upper limit of the endocervical canal called the internal os or isthmus marks the transition from the endocervix to the endometrium The endocervical canal has a fusiform shape and measures 7 to 8 mm at its widest in reproductive-aged women

5. The size and shape of the cervix vary widely with age, hormonal state, and parity. In the nulliparous female it is barrel shaped with a small circular external Os at the center of the cervix. In Parous women, cervix is bulky and the external Os becomes slit-like

6. The squamocolumnar junction (SCJ) is defined as the junction between the squamous epithelium and the columnar epithelium. Its location on the cervix is variable Age and hormonal status are the most important factors influencing location of SCJ. At birth and during premenarchal years, the SCJ is located at or very close to the external os (original SCJ) During reproductive age, the SCJ is located at variable distances from the external os In a postmenopausal woman, the new SCJ is not visible and has receded into the endocervix

7. Histology Of Normal Cervix The Ectocervix is covered by non-keratinizing, stratified squamous epithelium , either native or Metaplastic in continuity with the vaginal epithelium. The squamous epithelium is composed by multiple layers: basal, parabasal intermediate and superficial layer The Endocervix is lined by a simple columnar epithelium that secretes mucus. Mucinous columnar epithelium lines the surface and the underlying glands

8. TRANSFORMATION ZONE (TZ) Area around the opening of cervix where the endocervix and ectocervix come together It contains both glandular cells from endocervix and squamous cells from ectocervix TZ has large area of immature squamous epithelium and is particularly vulnerable to HPV infection as it lacks the typical micro ridges seen in mature squamous epithelium

9. Why are SCJ and TZ important ? Recent studies indicate SCJ to be a site of “embryonic cell population”. The reserve cells are the progeny of embryonic cells with different susceptibilities to infection by HPV and therefore involved in malignant transformation. The TZ is the site of origin for > 90%of precancerous lesions also called squamous intraepithelial lesions (CIN) and cancers.

10. PREMALIGNANT DISEASE OF CERVIX

11. CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN) CIN means disordered growth and development of the epithelial lining of cervix Various degrees of CIN CIN I or mild dysplasia means disordered growth of lower 1/3 of epithelium CIN II or moderate dysplasia means disordered growth of lower 2/3 of epithelial lining CIN III or severe dysplasia or carcinoma in situ represents more than 2/3 or full thickness epithelial dysmaturity Often multicentric ,since lower genital tract is embryologically derived from same anogenital epithelium CIN, VIN, VAIN & PAIN often coexist in about 10-20% of patients

12. PATHOGENESIS CIN is most commonly detected in women in their 20s , peak incidence is between 25-35 years Risk factors are : Multiple sexual partners Early onset of sexual activity HPV infection Lower genital tract neoplasia STDs Smoking HIV infection/AIDS Immuno supressant drugs or conditions immunity causing low Multiparity Prolonged use of COCPs

13. HPV is the prime etiologic factor for CIN and CA cervix Double stranded DNA virus > 100 sub types . Most common high risk HPV sub types are 16 (50-70%) and 18(7-20%) ,31, 33 and 45 HPV is present in > 80% of all CIN lesions and > 99.7% of CA Cervix . In vast majority of women , there is 90% spontaneous resolution of HPV infection. In few women it persists, where it triggers an oncogenic process in the region of TZ , wheremetaplasia occurs . HPV alone is insufficient to cause CIN or CA cervix Smoking and HPV have a synergistic effect on the developing of CIN Cigarette smoke carcinogens accumulate locally in cervical mucus

14. PREVENTION HPV VACCINE SCREENING

15. PREVENTION (CONTD) HPV VACCINATION: Centre for disease control and prevention (CDC) has recommended that all girls between 11-26 years of age should be offered HPV vaccine ( 3 doses ) It offers protection in 93-100% of the cases Initially bivalent vaccine was used which offered protection against sub types 16 &18 only Now quadrivalent vaccines are used which are protective against all sub types FDA has approved vaccination in the males aged 9-26 years of age as well to provide protection against acquiring genital warts and development of anal intraepithelial neoplasia and anal cancer

16. PREVENTION (CONTD) SCREENING : With effective screening programme in developed countries ,there has been 75% reduction in CIN & CA cervix Screening involves 3 parts : Cervical cytology screening HPV testing Visual screening

17. PAP SMEAR

18. INTRODUCTION The “Pap test saves lives.” In 1940’s, Dr. G. N. Papanicolaou first developed the technique of collecting, fixation, and staining of cervical cells (Pap smear). Today, it has become a revolutionary technique and a method of choice for the diagnosis of precancerous and cancerous changes in the uterine cervix.

19. Types of pap smear devices

20. Equipment for pap smear

21. The Pap smear can be used as a screening test for: Population screening by organizing camps in urban and rural areas. Opportunistic screening method – meaning that all eligible women visiting any hospital or any gynecology outpatient department for any other reason undergoes a Pap smear. Screening using a Pap test – either conventional or liquid-based cytology (LBC) has stood the test of time. A systematically collected smear from the SCJ, well fixed, and well stained is still the best method to detect abnormalities in the cervical epithelium preceding invasive cancer. These abnormalities can be then confirmed through a directed biopsy, collected during colposcopy , and later ablated either by cryotherapy or loop electrosurgical excision procedure/large loop excision of the TZ.

22. INSTRUCTION TO THE PATIENT To come during the postmenstrual period or best between the 14 th and 28 th day of cycle (premenstrual period) Not to come when there is active bleeding. First 3–4 days of menstruation are best avoided although not a contraindication To avoid intercourse on the previous day as the contamination with semen can obscure squamous cell morphology and large seminal vesicle cells can mimic atypical squamous cells To avoid douching with any antiseptic solution Not to insert any vaginal tablets as a part of ongoing treatment (need to be withheld or smear collection is done after completion of treatment Or a cervical biopsy or cryotherapy or any other procedure has been done in the past 6 weeks. Regeneration atypia in squamous cells can be a cause of overinterpretation of epithelial abnormalities.

23. TECHNIQUE OF PAP SMEAR Explain the procedure to the patient and take a verbal or informed consent The patient is instructed to lie in a lithotomy position – ideally on a PV table A Sim’s speculum or a bivalve Cusco’s speculum is inserted in the vagina and the cervix is exposed with gentle maneuvering of the speculum. The long end of the tip of any of the spatulas or the tip of the brush is put in the endocervical canal and fixed gently but firmly and then rotated clockwise through 360° 2–3 times and 5 times if the Cervex brush is used. With the cytobrush and Cervex brush –reverse rotation during the procedure is strictly prohibited as it may leave behind those cells that are collected in the previous rotations The material is spread in a circular or linear fashion in the central 2/3 rd area of the glass slide leaving the edges of the glass slide free

24. For LBC preparation, the Cervex brush is broken away or detached from the stick and tip of the Cervex brush is dropped in the LBC vial containing fixative The conventional smear is immediately fixed in absolute alcohol. Delay in fixation causes air drying artifacts and there is clouding of morphological details However, if there is shortage of alcohol or constant failure to provide “good quality wet fixed smears,” then the smear may be totally air dried. The air dried smears are rehydrated in the laboratory

25. Cervical cytology screening : also known as PAP SMEAR should begin after the age of 21 years and not earlier Should be done every 3 years in women aged 21-29 years After the age of 30 years both HPV and cervical screening should be done every 5 years Exfoliated cells from the cervix are collected to prepare a slide and examined under microscope .

26. Screening should discontinue after 65 years of age , with negative PAP smear consecutively in past 10 years It should also be discontinued after TAH HIV positive women should be screened twice a year for 1 st year after diagnosis and thereafter annually Bethesda system is used to classify the cytological smears of cervix into low grade squamous intraepithelial neoplasia ie CIN I and high grade ie CIN II & CIN III

27. HPV TESTING: Done as a screening test along with PAP smear in women aged 30 years or more . If primary screening is negative then it should not be repeated earlier than 5 years Also indicated in follow up treatment for CIN II / III

28. VISUAL SCREENING : Used as a screening tool in low resource setting It has limited specificity but is economical Visual inspection of cervix can be performed directly with speculum or by cervicoscopy using acetic acid , toludine blue or lugols iodine

29. COLPOSCOPY Examination of magnified cervix using a light source Used for both diagnostic and treatment purpose P/S exam is done and colposcopy performed Acetic acid and Lugol s iodine solution is applied to the cervix The abnormal areas of cervix are highlighted by these solutions and biopsy taken from these areas Acetic acid coagulates the nucleoproteins in the abnormal cells and makes them white . Hence these aceto white areas are biopsied With Lugols iodine CIN areas fail to stain brown because they lack intracytoplasmic glycogen New vessel formation over areas of CIN is also seen under colposcopy

30. CLINICAL FEATURES: Usually asymptomatic Clinically suspicious looking cervix Intra menstrual /post coital bleeding p/v Vaginal discharge

31. CLASSIFICATION OF CIN The proportion of cervical epithelium exhibiting the dysplastic cells determine the grades of CIN CIN 1 (low grade dysplasia ), involves the lower 1/3 or < of the epithelium CIN 2 (high grade dysplasia ) involves lower 2/3 of the epithelium CIN 3 (high grade ) involves full thickness of epithelium

32. ABNORMAL PAP SMEAR

33. SPECIAL EXAMINATIONS : All abnormal cervical cytology tests require further evaluation to exclude CA cervix and to determine the extent of CIN. They include : Repeat PAP smear HPV testing Colposcopy

34. Repeat PAP smear : Patient showing CIN 1 should be treated with antibiotics first before repeat PAP smear All women between 21 – 24years age , with low grade squamous intraepithelial lesion (LGSIL) have a very high rate of spontaneous regression to normal . Therefore they will require repeat smear at 12 months interval. This same group of women with high grade lesions(HGSIL) will require repeat PAP smear followed by Colposcopy . Women older than 24 years, premenopausal LGSIL, HGSIL or atypical glandular cells (AGCs) should be immediately reffered for colposcopy and excisional biopsy

35. Indications for colposcopy : Abnormal PAP smear or HPV testing Suspicious looking cx Postcoital or intermenstrual bleeding p/v Vulvar /vaginal neoplasia

36. Abnormal colposcopic findings : Leukoplakia or hyperkeratosis Aceto -white epithelium Abnormal vascular pattern in the form of mosaicism or puntuation Atypical vessels Further evaluation of these findings are done by colposcopically directed punch biopsy & endocervical sampling with a brush .

37. DIAGNOSTIC CONIZATION : Indicated: after unsatisfactory colposcopy If the lesion extends in the endocervical canal If there is dysplasia on endocervical sampling If microinvasive carcinoma is suspected COMPLICATIONS OF CIN 30-40% of CIN III lesions progress to carcinoma of cervix

38. TREATMENT : EXPECTANT TREATMENT PROPER

39. EXPECTANT MANAGEMENT: Appropriate for CIN I patients , as > 80% cases will regress to normal .follow up is required for 2 years by PAP smear at 6 monthly intervals and HPV test annually .

40. TREATMENT PROPER : It consist of : Surgical conization Cold knife conization Laser cone excision Large loop excision of TZ (LLETZ) Cryotherapy CO2 laser ablation

41. CRYOTHERAPY : Outdoor procedure Done without anaesthesia It includes freezing the lesion with cryoprobe dipped in NO2 or CO2 Low cost Easily available Low rate of complications As it is an ablative procedure , hence further colposcopic examination for follow up cannot be done LLETZ : Used to treat CIN II/III lesions Main advantage is that tissue is provided for histology Clinically effective in > 95%of patients , cost effective

42. COLD KNIFE CONIZATION: Cone shaped portion of cervix is removed with a knife and sent for histology Done in OT under anaesthesia Bleeding , infection, cervical stenosis and incompetant cervix can occur

43. PROGNOSIS: 80-90% success rate in treatment of CIN , regardless of treatment modality used . Follow up is done by 6 monthly PAP smear and annual HPV testing for 2 years ,followed by long term annual surveillance . RECURRENCE --- 4.6% , treated by TAH if family is complete

44. Special Case: Pregnancy Only diagnosis which alters clinical management of the pregnancy is invasive cancer If screening suggests high risk for CIN-2/3+, patient should undergo colposcopy without endocervical sampling If low risk for CIN-2/3+, either colposcopy as above or wait 8-12 weeks postpartum

45. Special Case: Younger Women Spontaneous resolution of CIN-1 and CIN-2 occurs at 80% and 50% rates Most HPV+ infections resolve within 24 months Risk of invasive cancer approaches zero For these reasons, no cervical cancer screening is recommended for patients age 20 or younger