CARCINOMA CERVIX. Dr. PREETHI REDDY. B. M S OBG II yr POST GRADUATE.

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1 CARCINOMA CERVIX Dr. PREETHI REDDY. B M S OBG II yr POST GRADUATE.

2 Introduction Cervical cancer is the second most common female malignancy worldwide. It is responsible for 4,66,000 deaths annually worldwide and of these 75% are from developing countries. In india alone 1,30,000 new cases found annually, 70,000 deaths occurred every year.

3 Invasive cancer of cervix is considered to be a preventable condition. Associated with long pre-invasive stage(cervical intraepithelial neoplasia) making it amenable to screening and treatment.

4 Incidence Incidence of cervical cancer is steadily declining in the developed world. Pap smear has reduced : - incidence of cervical cancer : 79% -mortality : 70%.

5 Age Mean age : 47 yrs. Distribution of cases is bimodal, with peaks at and yrs of age.

6 Risk factors

7 Poor medical care Uncircumscribed men Chromosomal aberrations smoking Usage of combined oral contraceptives over a period of 8yrs. Infectious agents : Human papilloma virus( HPV) HIV Chlamydia trachomatis

8 Risk factors contd

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10 Smoking Damages DNA in cervical epithelium Polycyclic hydrocarbon DNA adducts Induction of mutations. High levels of smoke derived nicotine present in the cervical mucous may act alone or in association with HPV in the development of the disease.

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12 HUMAN PAPILLOMA VIRUS Initiating event in cervical dysplasia and carcinogenesis is infection with HPV. Causative agent of both squamous and adenocarcinoma. Morethan 100 types, >30 of which can affect the lower genital tract. 14 high risk HPV types. HPV 16 and 18 are found in up to 62% of cases.

13 Pathogenesis of HPV infection: HPV is epitheliotropic infects cervical epithelium latent infection or active infection with viral replication HPV integration into human genome upregulation of viral oncogenes

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15 Predisposing factors: Cervical dysplasia. Cervical intraepithelial neoplasia Carcinoma in situ The lesion proceeds the invasion by years.

16 Symptoms

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18 Bladder symptoms: increased frequency, dysuria hematuria Rectal involvement: diarrhoea rectal pain bleeding per rectum Ureteric obstruction: result in frequent attacks of pyelonephritis.

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21 Diagnosis PAP test. Obvious growth cervical biopsy Gross disease not there colposcopy guided biopsy.

22 PAP TEST

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24 More frequent testing : HIV positive women Immunosuppressed DES daughters Those with history of CIN 2 or greater. Screening can be stopped at age 70 if there is no abnormal result in past 10yrs.

25 Cytology Histology colposcopy

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27 Other investigations: complete blood picture Complete urine examination Ultra sonography Liver function tests Renal function tests IVP - hydronephrosis MRI- Parametrial involvement PET pelvic and para-aortic node involovement. Cystoscopy.

28 Staging of Cervical Carcinoma Staging according to FIGO is always performed pre-operatively based on clinical examination. Exception: IA diagnosed histologically.

29 Ⅰa Ⅰb Ⅱa Ⅰa1 Ⅰa2 Ⅰb1 Ⅰb2 Ⅱb Ⅲa Ⅲb Ⅳa Ⅳb

30 Carcinoma of the cervix uteri- FIGO 2009 Stage I The carcinoma is strictly confined to the cervix (extension to the corpus would be disregarded) IA Invasive carcinoma which can be diagnosed only by microscopy, with deepest invasion <5 mm and the largest extension <7 mm IA1 Measured stromal invasion of <3.0 mm in depth and extension of <7.0 mm IA2 Measured stromal invasion of >3.0 mm and not >5.0 mm with an extension of not >7.0 mm

31 IB Clinically visible lesions limited to the cervix uteri or pre-clinical cancers greater than stage IA IB1Clinically visible lesion <4.0 cm in greatest dimension IB2Clinically visible lesion >4.0 cm in greatest dimension

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33 Carcinoma of the cervix uteri- FIGO 2009 Stage II Cervical carcinoma invades beyond the uterus, but not to the pelvic wall or to the lowerthird of the vagina IIA Without parametrial invasion IIA1 Clinically visible lesion <4.0 cm in greatest dimension IIA2 Clinically visible lesion >4.0 cm in greatest dimension IIB With obvious parametrial invasion

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35 Stage III The tumour extends to the pelvic wall and/or involves lower third of the vagina and/or causes hydronephrosis or non-functioning kidney IIIA Tumour involves lower third of the vagina, with no extension to the pelvic wall IIIB Extension to the pelvic wall and/or hydronephrosis or non-functioning kidney

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37 Stage IV The carcinoma has extended beyond the true pelvis or has involved (biopsy proven) themucosa of the bladder or rectum. IVA Spread of the growth to adjacent organs IVB Spread to distant organs

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39 Direct - Uterus - Vagina. - Parametrium. - Bladder and rectum. SPREAD: Lymphatic A- primary node: parametrial. Paracervical. Vesicovaginal. Rectovaginal. Hypogastric. Obturator and external iliac Dissemination (late) - parametrial spread causes obstruction of the ureters, many deaths occur due to uraemia. - Obstruction to the cervical canal results in pyometra. B-Secondary nodes: Common iliac Sacral Paraaortic Inguinal.

40 Incidence of lymphnode involvement stage Pelvic nodes % Para aortic nodes 1A A2 4.8 <1 1B II A IIB III IVA 55 40

41 TREATMENT Surgical. Radiotherapy. Radiotherapy & Surgery. Radiotherapy and Chemotherapy followed by Surgery. Palliative treatment.

42 Treatment decision is based on the pathological condition: depth of invasion width and breadth of invasion presence or absence of lymphovascular invasion. margin status.

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44 STAGE PELVIC LN INVOLVEMENT SURGERY IB2 IIA1 IIA2 IIB IIIA IIIB 16 24% TYPE III RADICAL H. + PELVIC AND PARA AORTIC LYMPHADENECTOMY with CHEMO-RADIATION. TYPE III RADICAL HYSTERECTOMY + PELVIC AND PARAAORTIC LYMPHADENECTOMY or PRIMARY CHEMORADIATION % PRIMARY CHEMORADIATION IVA 55% PRIMARY CHEMORADIATION OR PRIMARY EXENTERATION IVB PRIMARY CHEMOTHERAPY OR RADIATION

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46 Surgery offers several advantage It allows preservation of the ovaries (radiotherapy will destroythem). There is better chance of preserving sexual function. Vaginal stenosis occur in up 85% of irradiates. Psychological feeling of removing the disease from the body. More acute staging and

47 COMPLICATIONS OF SURGERY Haemorrhage: primary or secondary. Injury to the bladder, ureters. Fistula uretero-vaginal -vesico vaginal Pulmonary embolus Bladder dysfunction. Lymphocoele. Shortening of the vagina.

48 RADIOTHERAPY

49 Radiotherapy PRIMARY RADIATION THERAPY External irradiation (Teletherapy). Intracavitary radiation (Brachytherapy). a) Low Dose Radiation: caesium-137 b)high Dose Radiation: Iridium-192

50 INTENSITY MODULATED RADIOTHERAPY: This distinguishes between target treatment volume and normal tissue. Therefore delivers radiation to the specified treatment volume sparing the adjacent normal tissue.

51 ADJUVANT RADIOTHERAPY: Post operative radiotherapy. Recommended for patients with high and intermediate risk factors i.e., metastasis to lymphnodes Positive surgical margins Invasion of paracervical tissue Deep cervical invasion.

52 CONCURRENT CHEMORADIATION: It encompasses the benefit of systemic chemotherapy with benefits of regional radiotherapy. CISPLATIN based chemotherapy is found more effective than hydroxyurea based treatment.

53 THE OVERALL 5 YEARS SURVIVAL FOLLOWING THERAPY: Stage I % Stage II % Stage III % Stage IV %

54 Follow up Patients who received radiotherapy should be monitered closely. Tumours are expected to regress for up to 3 months after radiotherapy. During followup visit: Pelvic examination: a) progressive shrinkage of the cervix. b) possible stenosis of cervical os and upper vagina.

55 Rectovaginal examination: uterosacral and cardinal ligaments are palpated for nodularity. Supraclavicular and inguinal lymphnodes are palpated. Cervical and vaginal assessment should be performed : every 3months- 2yrs. : every 6months- 3yrs. Radiography of the chest may be performed yearly in patients with advanced disease.

56 Objective Cancer cervix is still quite common, reduction in incidence depends on the quality of the screening program.

57 The aetiology appears to be multifactorial the prime oncogenic agent is probably [HPV- 16,18]. Important step in primary prevention is development of prophylactic vaccine to protect against HPV infection.

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59 HPV VACCINE Prophylactic vaccines - induce secretion of neutralising antibodies against : HPVcapsid protiens L1, L2 or cell surface binding receptor, hence prevent viral entrance into human kertainocytes. Capsid protiens of HPV( L1, L2 ) co-assemble to form Virus-Like Particles(VLPs).

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61 Routine HPV vaccination is recommended for girls at yrs of age. Its given intramuscularly in 3 doses. 2 nd dose given 2 months after 1 st dose and 3 rd dose given 6months after 1 st dose. Screening practices for CIN and cancer cervix should remain unchanged in both vaccinated and unvaccinated women.

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