Recent advances on Cervical cancer .pptx

Presentation on CIN, Cervical cancer and HPV Vaccines

1. Cervical Cancer (Recent advances) Presenter: Dr Vinaya Hugar

2. Introduction Carcinoma of the cervix is the fourth most common cancer among women worldwide and is now attributable to infection with human papillomavirus (HPV) It is the most common genital cancer among women in India. It now ranks second to carcinoma of the breast amongst cancers in women The universal application of Pap smears in western communities has led to a drastic decline in the number of invasive cancers of the cervix and a higher detection of preinvasive lesions

3. Introduction Every year 530,000 new cases and 275,000 deaths are reported annually worldwide In India: 130,000 new cases occur with a death toll of 70,000 cases every year In India, the incidence is 20-35/100,000 women between 35 and 65 years I n developed countries, where screening programmes are on, the incidence of invasive cancer of cervix has fallen to 8/100,000 women.

4. Cancer Incidence : India

5. WHO Cervical Cancer Elimination Strategy WHO has outlined a new approach for reducing incidence of cancer cervix to 4/100,000 women by year 2030. The 90-70-90 approach is outlined as follows: 90% of girls fully vaccinated with HPV vaccine by the age of 15 years 70% of women are screened with a high-performance test by 35 years of age and again by 45 years of age 90% of women identified with cervical disease receive treatment

6. Predisposing factors for Ca Cervix HPV infection Coitus before the age of 18 years Multiple sexual partners Delivery of the first baby before the age of 20 years Multiparity with poor spacing between pregnancies Sexually transmitted diseases Poor personal hygiene Poor socioeconomic status Smoking and drug abuse, including alcohol Immunosuppressed individuals Women with preinvasive lesions of cervix Use of OCPs

7. CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN) Most cancers of cervix begin in the region of squamocolumnar junction. Before actual development of cancer cervix, there are changes in the epithelium in the region of transformation zone; these changes can be picked up on cytology These changes have been named cervical dysplasia , cervical intra epithelial neoplasia ( CIN ) and lately as squamous intraepithelial lesions ( SIL )

8. CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN) Cervical dysplasia - cytological term CIN- histopathological description in which a part or the full thickness of the stratified squamous epithelium is replaced by cells showing varying degrees of dysplasia The cells vary in size, shape and polarity. There is an alteration in the nuclear cytoplasmic ratio, and the cells reveal large, irregular, hyperchromatic nuclei with marginal condensation of chromatin material and mitotic figures

9. Dysplasia Mild dysplasia (CIN-1): undifferentiated cells are confined to the lower one-third of the epithelium. Moderate dysplasia (CIN-II): Undifferentiated cells occupy the lower 50%-75% of the epithelial thickness. Severe dysplasia and carcinoma in situ (CIN-III): In this grade of dysplasia, the entire thickness of the epithelium is replaced by abnormal cells Bethesda classification Low-grade squamous intraepithelial lesions ( LSIL ): CIN-I High-grade squamous intraepithelial lesions ( HSIL ): CIN-II and CIN-Ill

10. Pap smear screening

11. Comparison of Different Methods of Treatment of Dysplasia and CIN

12. TREATMENT OF CERVICAL DYSPLASIA Low- grade SIL

13. Management of CIN

14. PREVENTION OF CANCER OF THE CERVIX The success of screening programme world over shows that it is a preventable cancer. Effective screening by Pap smear , VIA /VILI and HPV testing can detect most of the lesions in preinvasive stage HPV vaccine is now available, although it is expensive as of today. Given to adolescents before exposure to the virus (before sexual activity begins), a high protection rate is expected

15. Cytology (Pap Smear) Most commonly employed screening method The Papanicolaou smear, a routine screening test for cancer of the uterine cervix, was reported in 1928, and its efficacy was proved by 1941 Reduced mortality by cervical cancer by 70% in developed countries since 1950

16. Visual inspection methods Low cost and effective method of screening in low resource setting s Offers immediate diagnosis & possibility of simultaneous treatment Comparable sensitivity to Pap smear Drawback is lower specificity Not reliable in post-menopausal women

17. CDC WHO IAP 2 dose (0,6 month) 9-13 year 9-14 year 3 dose (0,1,6) (0,2,6) 11-12 years 13-26 years( if not vaccinated before) >15 year Immunocompromised >15 years Immunocompromised HPV Immunization Guidelines

18. Cervarix Gardasil Gardasil-9 Company GlaxoSmithKline, Brentford , UK Merck, Kenilworth, NJ Bivalent Quadrivalent nonavalent Serotypes 16, 18 ( cross protection against 45,31) 16,18,6,11 6,11,16,18, 31,33,45,52,58 Age groups 10-45 years 9-45 years Adjuvant Aluminium sulphate Dosage 0,1,6 0,6 0,2,6 0,6 0,1,6 Efficacy 98% against CIN 2 98% against CIN 2 100% -VAIN, VIN, genital warts Active against Cervical cancer Cervical cancer, genital wart Cervical, vulval , vaginal HPV Vaccination

19. Invasive cancer of cervix Majority of the invasive cancers of cervix are squamous cell carcinomas I n 10%-20% of cases, these carcinomas are adenocarcinoma in histology HISTOLOGICAL CLASSIFICATION: Adenocarcinoma Adenosquamous carcinoma Clear cell carcinoma Rare type- neuroendocrine carcinoma

20. HPV Non enveloped double - stranded DNA virus

21. HPV Oncogenesis HPV integration into host cells (not just infection) necessary Integration causes expression of E6 , E7 oncogenic proteins Uncontrolled degradation of p53 by E6 (thus inhibition of apoptosis) , E7 binds pRb (leads to continuous activation of the cell cycle) Dr. Harald zur Hausen et al received the Nobel Prize in Medicine in 2008 for isolating oncogenic HPV strains and elucidating the oncogenic process

22. Mechanism of HPV transmission & Acquisition Sexual contact Through sexual intercourse Genital–genital, manual–genital, oral–genital Genital HPV infection in virgins rare, but may result from non-penetrative sexual contact Proper condom use may reduce the risk, but not fully protective against infection Nonsexual routes Mother to newborn (vertical transmission) Fomites (e.g., undergarments, surgical gloves, biopsy forceps)- Hypothesized but not well documented; would be rare

23. Spectrum of Changes in Cervical Squamous Epithelium Caused by HPV Infection Normal Cervix HPV Infection / CIN* 1 CIN 2 / CIN 3 / Cervical Cancer

24. Clinical features Irregular menses Menometrorrhagia Continuous bleeding Postcoital bleeding Leucorrhoea  Blood-stained or offensive discharge.

25. DIFFERENTIAL DIAGNOSIS The cervical growth and ulcer may at times be mistaken for Tubercular and syphilitic ulcer Mucus and fibroid polyp Rarely sarcoma of the cervix Biopsy helps in ruling out other conditions

26. STAGING OF CANCER OF THE CERVIX (REVISED FIGO STAGING 2018)

27. Treatment of invasive cancer Treatment depends on the stage of the disease. I n case there is a need to preserve fertility, a conservative surgical procedure is possible in early-stage disease Better understanding of early lesions has permitted a more conservative surgical treatment without compromising the success

28. Surgical treatment Stage Ia 1 : conization with a clear margin is considered adequate and is diagnostic as well as therapeutic. Hysterectomy ( extrafacial hysterectomy - Type I hysterectomy) is appropriate in elderly and parous women, or those having an associated disease in the uterus. Stage Ia 2: Extended hysterectomy and lymph node sampling are recommended (Type II hysterectomy), Fertility-conserving trachelectomy

29. Surgical treatment  Stages Ib and Ila : Radical Abdominal hysterectomy (Type III radical hysterectomy)  Schauta's vaginal hysterectomy (known as Mitra operation in India) and Taussig's or laparoscopic lymphadenectomy Primary radiotherapy with concurrent chemotherapy Combined surgery and radiotherapy

30. Radiotherapy R adiotherapy is applicable in stages such as Stages Ilb , Illa and Illb where surgery is not feasible. Primary radiotherapy consists of intracavity brachytherapy and external radiation to the pelvis. It yields the same 5-year cure rate as that of surgery, i.e. 80%-90%. M any surgical cases show positive lymph node metastasis which requires additional postoperative radiotherapy anyway, and this combined therapy increases the morbidity in the woman

31. Chemotherapy Addition of chemotherapy with cisplatin weekly to radiotherapy improves the radiation effect, as cisplatin acts as a radiosensitizer agent. Current standard of radiation therapy is to combine it with weekly cisplatin when the patient is undergoing external beam radiation.

32. Indications for Postoperative Radiotherapy Positive lymph nodes for metastasis Positive resected margin of vagina or parametrium Evidence of lymphovascular invasion or deep stromal invasion Poorly differentiated tumour

33. Thank you