1. In India “Your cooperation is needed” Down staging of cervical cancer Dr. Sharda Jain Director: Global Institute of Gynaecoloy at Pushpanjali Crosslay Hospital Secretary general: Delhi Gynaecologist Forum

2. Early Carcinoma Advanced Carcinoma

3. Global Burden of Cervical Cancer Worldwide, 500,000 women diagnosed per year 1 270,000 deaths per year 1 >1 million new cases of cervical cancer each year, 2050 2 One Death every 2 minutes

4. Cancer Cervix World - No. - 2 New - 5 Lack Deaths - 2.75 India Number One New – 1.32 lack Deaths - o.74 lack One death every 7th minutes in India

5. Cancer Cervix Life Time Risk India = 20 – 35 / lack (35 – 64 yrs) Developed countries = 1-8/ lack It is expected by 2050 = double If no action is taken

6. Most effective program of down staging of cervical Cancer is paps smear screening PATH (prog. Of appro. tech in Health)

7. MASS PAPS SMEAR SCREENING {IARC - Int. agency of research on cancer } 35 – 64 yrs = 93% reduction if Screening 1-3 years = 84 % Reduction 5 years = 64% reduction 10years India No Govt. Effort for public Screening (non availability of Tech/ doctors to read paps smear )

8. Alternative methods for down staging of the cervical cancer 1.VISUAL INSPECTION OF CERVIX WITH ACETIC ACID. (VIA) 2.Use of MAGNASCOPE instead of colposcope 3.SINGLE VISIT APPROACH i.e.Treatment with cryosurgery for VIA +ve women 4. SELF COLLECTED SAMPLE for cytology or HPV – DNA testing

9. 5. Education and counseling 6. Increase coverage by camp approach 7. Low cost HPV test 8. HPV Vaccines. Alternative methods for down staging of the cervical cancer

10. VIA AFTER APPLYING 3 % ACETIC ACID TO CERVIX “WHITE PATCHES” APPEARS DUE TO COAGULATION OF CELLULAR PROTEINS AND INDICATE THE ABNORMAL EPITHELIUM WHICH IS THICK AND DOES NOT ALLOW THE LIGHT REACTION TO PASS THROUGH. CERVICAL BIOPSIES - LSIL/HSIL

13. Women were examined visually by simple speculum and colposcopically after application of 3 % acetic acid to cervix. Equal detection rates of cervical abnormalities by both techniques. Ottaviano and la torre 1982,

14. VILI WHEN LUGOL’S IODINE IS APPLIED TO THE CERVIX, THE NORMAL CELLS CONTAINING GLYCOGEN STAIN DARK BROWN. THE ABNORMAL CELLS ARE RAPIDLY DIVIDING AND ARE DEFICIENT IN GLYCOGEN HENCE, REMAIN UNSTAINED WHICH ARE FURTHER EVALUATED BY COLPOSCOPY & BIOPSY.

17. IARC studies in India and Africa proved that VIA performed by trained paramedics has sensitivity of 64 to 90% and specificity of 73 to 91% which is comparable to conventional cytology. specificity of VIA was increased by adding adjunctive test like VILI. Advantages of visual technique are immediate results, making cost effective and has more than 99% negative predictive value. muwonge R (2007)

18. Sensitivity and specificity are often used to summarise the performance of a diagnostic test. Sensitivity is the probability of testing positive if the disease is truly present. Specificity is the probability of testing negative if the disease is truly absent.

19. Who Needs colposcopy ± Biopsy Ten to fifteen percent VIA+ve women require referral for colposcopy & colposcopic guided biopsies.

20. LSIL / LGSIL Conservative treatment and follow up subsequently 6 monthly.

21. HSIL / Cancer Specialized Treatment

22. In single visit approach cryo therapy is offered to all those women who are VIA +ve and cannot visit more than once for treatment. What Is Single Visit approach?

23. Tamil Nadu Study Single Visit approach - follow up after 7 years showed 25% reduction in cervical cancer incidence 35% reduction in cervical cancer mortality 27.5% reduction in the incidence of stage II or advanced cancer compared to control group.

24. What should be Indian Govt. Approach Cervical cancer Should be taken seriously for ↓ number & reduction in mortality. Camp approach Single visit approach Both can help to down stage the disease in resource poor settings like India. Self sampling in rural areas/ slums Pap Smear/ HPV

25. HPV Infection

26. 100% of cervical cancers are caused by HPV

27. 93.5% of all cancer caused by HPV is Cervical Cancer

28. In India over 90% of Cervical Cancers are Caused by 5 HPV Types: HPV 16, 18, 45, 31 and 33 2 100 HPV Types Have Been Identified 1 30 HPV Types are Transmitted by Genital skin to skin Contact 15 HPV Types are Oncogenic Human Papillomavirus (HPV)

29. In India, HPV 16, 18, 31, 33 & 45 account for >92% Squamous Cell Carcinoma >95% Cervical Adenocarcinom a

30. Adenocarcinoma is difficult to detect with routine screening methods 1 –The cervical smear brush cannot access the endocervical canal as easily as the outer surface of the cervix 1 Adenocarcinoma is difficult to detect Adenocarcinoma: may be inaccessible to the cervical smear brush Squamous cell carcinoma: usually accessible to the cervical smear brush Cervical smear brush Cervix

31. Adenocarcinoma of the cervix- An Emerging concern Incidence increasing (20–25% of all cervical cancers), not prevented with traditional pap screening More aggressive and occurs in younger women > 90% of adenocarcinomas result from HPV 16, 18, 45, 33 and 31 1 HPV 18 confers the highest risk

32. Every woman is at risk of Cervical Cancer HPV infections are very common The risk starts from sexual debut 1 and continues throughout life 2

33. Up to 80% of women will acquire an HPV infection in their lifetime 5–7 HPV infections continue to occur in women over 25 years of age

34. Low-grade squamous intraepithelial lesion (ASCUS/LSIL) High-grade squamous intraepithelial lesion (HSIL) Invasive carcinoma Time Years Months Normal epithelium HPV infection koilocytosis CIN1 CIN2 CIN3 Regression Progression* Progression of Cervical Disease

35. The need for Vaccination against Cervical Cancer

36. HPV-containing double stranded DNA ‘Empty’ non-infectious virus- like particle (VLP) mimics the virus Virus-like particles (VLPs) as HPV vaccine antigens mimic the virus structure Stanley M, et al. Vaccine 2006; 24(suppl 3):S3/106–113.

37. Why vaccination is needed ?? No protection through natural infection as HPV evades the immune system Vaccines are highly immunogenic Higher the serum antibodies, more is local neutralising antibody & longer the protection

38. HPV types and cervical cancer 1. Bosch FX et al. Vaccine 2008; 26S: K1–16. 2. Bhatla N et al. Vaccine 2008; 26(23):2811-2817. Five most frequent and aggressive HPV types that cause cervical cancer worldwide +++ HPV 16HPV 18HPV 45HPV 31 HPV 33 + These 5 HPV types are responsible for up to 92% of Cervical Cancer in India 2

39. 2 Vaccines Gardasil Cerverix

40. HPV Type% Efficacy(96.1% CI) ** HPV 16/18*98.4% 1 (90.4-100) 1 HPV 31*100% 2 (78.3-100) 2 HPV 33*72.3% 2 (19.1-92.5) 2 HPV 45*100% 2 (-19.5-100) 2 HPV 31, 33, 35, 39, 45, 51, 52, 56, 58, 59* 68.4% 2 (45.7-82.4) 2 * The total vaccinated naive cohort (TVC-naive) included women who were given at least one vaccine dose, were evaluable for efficacy, and at baseline had normal cytology, were DNA negative for all 14 oncogenic HPV types investigated, and were seronegative for HPV-16 and HPV-18 (n=11641). ** Median follow-up of 39.5 months (post dose1) ***CIN2+ was defined histologically as CIN2, CIN3, adenocarcinoma in situ, or invasive carcinoma References: 1. Paavonen J et al. Final Phase III Efficacy Analysis Of Cervarix™ In Young Women Abstract presented at the 25 th International Papillomavirus conference, Malmo, Sweden, 8-14 May 2009 2. Skinner R et al. Cross-protective efficacy of Cervarix against oncogenic HPV types beyond HPV-16/18: final analysis of cross- protection-PATRICIA study. Abstract presented at the 25 th International Papillomavirus conference, Malmo, Sweden, 8-14 May 2009 Cervarix™ efficacy: Summary

41. HPV vaccines: Safety and approval WHO’s Global Advisory Committee on Vaccine Safety (GACVS) concluded that the HPV vaccines had good safety profiles 1 U.S. Food and Drug Administration (FDA) approved both vaccines.

42. Potential impact of HPV Vaccination HPV vaccination is the primary prevention strategy against cervical cancer HPV vaccination is predicted to have a major impact on the burden of cervical cancer, especially in settings without optimal screening programs

43. FOGSI Recommendations Cervical cancer causes significant morbidity/ mortality HPV vaccine to be offered to all appropriate females who can afford the vaccine Vaccine should be given prior to sexual debut www.fogsi.org/hpv vaccine

44. When is the best time to vaccinate? Upto what age can the Vaccine be given

45. FOGSI Recommendations – Vaccine Schedule Age for initiation of vaccination is 10- 12 years. –Catch up vaccination is permitted up to 45 yrs Three doses at 0, 2 and 6 months with quadrivalent vaccine (Gardasil) Three doses 0, 1 and 6 months with bivalent vaccine (Cerverix) Intra muscular – Deltoid reason

46. FOGSI Recommendations Need for Booster At present there is no data to support use of boosters www.fogsi.org/hpv vaccine

47. Not recommended for use in pregnancy If patient becomes pregnant - Delay remaining doses till delivery If vaccinated during pregnancy - No intervention (MTP) needed Lactating women can receive the HPV vaccine and still continue breastfeeding as it is a vaccine without live viral DNA FOGSI Recommendations: Pregnancy & Lactation www.fogsi.org/hpv vaccine

48. Do we need to Screen before Vaccination? No! The results of screening will not influence to decision to vaccinate because: –Sexually active women continue to be at risk of new infections –Hence, vaccination will protect women from future infections regardless of an on going infection –NOTE: Vaccination will have NO effect on the on- going infection or lesion.