'EPIDEMIOLOGY AND DISEASE BURDEN OF CERVICAL CANCER'

1. 'EPIDEMIOLOGY AND DISEASE BURDEN OF CERVICAL CANCER'   Prof. Ravi Mehrotra MBBS (AFMC), MD, FRCPath, Ph.D. Director & Scientist G Institute of Cytology and Preventive Oncology. Noida rmehrotra@icmr.org.in Assocham Comp. Prev. Cx ca 7th Nov. 2013

2. ETIOLOGY • For years herpes was blamed as the cause of cervical cancer • In 1949 German researcher HaraldzurHausen first found HPV in warts found on humans. • 1976 Hausen proposed that HPV caused cervical cancer. His theory was initially rejected • HPV DNA was found in cervical cancer cells in 1983 and 1984 • HaraldzurHausen received the Nobel Prize for his discovery in 2008.

3. Spring 2011 PATEL, ROHAN K.

4. HUMAN PAPILLOMAVIRUSES • The epithelial lining of the anogenital tract is the target for infection by a group of mucosotropic viruses, the human papillomaviruses (HPVs). • Subclinical and clinical genital warts, also known as condylomataacuminata, and virtually all squamous cell cancers of the anogenital tract are caused by specific HPV types. • HPVs are DNA viruses with a genome size of about8000 base-pairs.

5. HUMAN PAPILLOMAVIRUSES • Human papillomaviruses are small icosahedral particles that infect the dermal layer of the skin. • There are more than 100 HPV types defined on the basis of DNA homology, of which more than 40 infect the anogenital tract. • The World Health Organization estimates that between 9-13% (~630million) of the world population has an HPV infection. 

6. HUMAN PAPILLOMAVIRUSES • Genital HPV types are typically divided into groups according to their presumed oncogenic potential. •ONCOGENIC HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68 oncogenic risk. •NON ONCOGENIC : 6, 11, 42, 43 and 44

7. NATURAL HISTORY OF CERVICAL CANCERS AND ITS STAGES

8. HOW THE DISEASE DEV. • HPV virus infection is a common infection .In most of the cases this infection resolve of its own but in very rare cases say one out of every 10 women the infection progresses and develops in early bad spot of cancer (pre cancerous lesion) .Prelimnary tests (Screening tests) like VIA, Pap, HPV can detect the disease in early stages and women can be treated easily .

9. HOW THE DISEASE DEV. • If HPV Infection remain persistent and the women still remain undiagnosed and with out treatment she may lead to cancer . • The signs and symptoms of the disease appear in late stages of the disease .so it is important that every normal woman between 30-59 years should undergo screening.

10. NATURAL HISTORY OF CERVICAL CANCER (WHO)

11. ~20% within 10 years HPV Infection Low- grade (CIN 1) High- grade (CIN 2/3) Invasive Cancer 60% 15% 10% in 2 years NATURAL HISTORY OF CERVICAL CANCER

12. NATURAL HISTORY OF CERVICAL CANCER HPV Infection Characteristics: HPV infection is extremely common among women of reproductive age. HPV infection can remain stable, lead to CIN, or become undetectable. Management: While genital warts resulting from HPV infection may be treated, there is no treatment that eradicates HPV. Primary prevention through use of condoms offers some protection. Low-grade CIN Characteristics: Low-grade CIN usually is temporary and disappears over time. Some cases, however, progress to high-grade CIN. It is not unusual for HPV to cause low-grade CIN within months or years of infection. Management: Low-grade CIN generally should be monitored rather than treated, since most lesions regress or do not progress. High-grade CIN Characteristics: High-grade CIN, the precursor of cervical cancer, is significantly less common than low-grade CIN. High-grade CIN can progress from low-grade CIN or, in some cases, directly from HPV infection. Management: High-grade CIN should be treated, because a significant proportion progresses to cancer. Invasive Cancer Characteristics: Women with high-grade CIN are at risk of developing invasive cancer; this generally occurs slowly, over a period of several years. Management: Treatment of invasive cancer is hospital-based, expensive, and often not effective. Screening strategies are intended to identify abnormalities in these ranges.

13. 10–15 years? Basement Membrane CIN 1 CIN 2 CIN 3 Invasive Cancer NATURAL HISTORY OF CERVICAL CANCER

14. STAGES OF CERVICAL CANCER

15. STAGES OF CERVICAL CANCER

16. INTERNATIONAL FEDRATION OF GYNECOLOGY AND OBSTRETRICS (FIGO) STAGING SYSTEM IA1       Confined to the cervix, diagnosed only by microscopy with invasion of < 3 mm in depth and lateral spread < 7 mm IA2       Confined to the cervix, diagnosed with microscopy with invasion of > 3 mm and < 5 mm with lateral spread < 7mm IB1       Clinically visible lesion or greater than A2, < 4 cm in greatest dimension IB2       Clinically visible lesion, > 4 cm in greatest dimension IIA1      Involvement of the upper two-thirds of the vagina, without parametrial invasion, < 4 cm in greatest dimension IIA2      > 4 cm in greatest dimension IIB        With parametrial involvement

17. IIIA : 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.IV The carcinoma has extended beyond the true pelvis or has involved (biopsy proven) the mucosa of the bladder or rectum. A bullous oedema, as such, does not permit a case to be allotted to Stage IV.IVA Spread of the growth to adjacent organs.IVB Spread to distant organs.

18. ASSOCIATED RISK FACTORS • AGE : Incidence increases with age from 25-45 then leveling off then finally decline. • Poor genital hygiene • low immunity • Repeated pregnancy • Promiscuity

19. ASSOCIATED RISK FACTORS • Low Socioeconomic Status. • Past and present occurrence of clinical genital warts. • Co-infections with other sexually transmitted infections etc . • Early marriage.

20. PREVENTIONS • Primary prevention - Immunization against HPV : Vaccines available for HPV 16&18 .Not included in immunization Schedule. GARDASIL CERVARIX

21. PREVENTIONS • Primary prevention - Health Education - Creating Awareness - Change in life style - Improving personal Hygine - Education about risk factors - Education about early signs and symptoms

22. IEC (INFORMATION ,EDUCATION & COMMUNICATION) EFFORTS • Community health education sessions. • One to one interaction by health workers with help of health education tools tailored to the need of community. • Propagation activities by means of Banners ,Posters , milking etc.

23. Flip chartPamphlet Information BrochuresPosters Banners Tailored to the need of the community and should be in local language HEALTH EDUCATION MATERIALS

24. ICPO’s HEALTH EDUCATION MATERIAL FLIP CHART

25. HEALTH WORKER WITH ICPO’s HEALTH EDUCATION MATERIAL

26. SECONDARY PREVENTION IDENTIFYING PRECURSOR LESIONS

27. IDENTIFYING PRECURSOR LESIONS • To screen for precursor lesions, clinicians must be able to identify normal and abnormal changes on the cervix.

28. Densely hyperkeratoticcondyloma Leukoplakia

29. ABNORMAL CERVICAL LESIONS • Leukoplakia and exophytic warts have an excess of keratin (keratosis) and appear white. • Precursor lesions (CIN) have an excess of cellular proteins and appear white after the application of dilute acetic acid. CIN lesions also lack glycogen, so they turn mustard- or banana-yellow after application of Lugol’s iodine.

30. CIN 1(Mild CIN) CIN 1 Source: Photograph courtesy of Dr. Renzo Barrasso.

31. CIN 2

32. CIN 1, 2, and 3 • It may be difficult to distinguish between CIN 1, 2, and 3 with the naked eye after staining with acetic acid or Lugol’s iodine. • They can be distinguished when biopsied for histologic examination and when a smear is examined cytologically.

33. CERVICAL CANCER Source: Photograph courtesy of Dr. Renzo Barrasso.

34. PREVENTION THROUGH SCREENING • Cervical cancer is preventable if detected early • The disease has a long pre-cancerous stage • Mild dysplasia – moderate dysplasia –severe dysplasia-Invasive cancer

35. TECHNOLOGIES: CERVICAL CANCER • CYTOLOGY • AIDED VISUAL • HPV

36. SCREENING TESTS FOR CERVICAL NEOPLASIA Cytology or Pap Smear - Conventional method Time tested method

37. CYTOLOGY: • Organized PAP smear screening programme is not possible due to lack of resources and skilled man-power • Also unable to achieve consistently high sensitivity and specificity in many settings

38. ALTERNATIVES TO CERVICAL CYTOLOGY Screening methods explored are: • Aided visual (VIA, VILI, VIAM) and • HPV screening.

39. VISUAL EXAMINATION • Visual alternatives are basically the visualization of cervix though P/S examination with a good light source.

40. AIDED VISUAL EXAMINATIONOF CERVIX • Immediate results and minimal requirements • Visual Examination of cervix using acetic acid (VIA) • Visual Examination of cervix using Lugols iodine (VILI) • Visual Examination of Cervix under magnification (VIAM)

41. Normal Cervix VIA Positive

42. HPV TESTING (HCII) • Detect High Risk HPV types • Sample from cervix- similar to PAP • Special transport medium needed • Processed in the Hi-teclab • Highest reproducibility • Expensive(20-30$) • Sensitivity (45.7 to 80.9%),Specificity (91.7 to 94.6%)

43. FLOW-CHART FOR SCREENING ACTIVITY Population in community Health education and motivation Target population Screening center screening *counseling *consent taking (Proforma filling) health education risk factor and s/s +ve -ve Follow-up and health education Refer for further diagnosis and management

44. BURDEN OF DISEASE

45. GLOBOCAN 2008 • Cervical cancer is the third most common cancer in women, and the seventh overall, with an estimated 530 000 new cases in 2008. • More than 85% of the global burden occurs in developing countries, where it accounts for 13% of all female cancers. • High-risk regions are Eastern and Western Africa (ASR greater then 30 per 100,000), Southern Africa (26.8 per 100,000), South-Central Asia (24.6 per 100,000), South America and Middle Africa (ASRs 23.9 and 23.0 per 100,000 respectively).

46. GLOBOCAN 2008 • Rates are lowest in Western Asia, Northern America • and Australia/New Zealand (ASRs less than 6 per 100,00). • Cervical cancer remains the most common cancer in women only in Eastern Africa, South-Central Asia and Melanesia.Overall, the mortality: incidence ratio is 52%, • Cervical cancer is responsible for 275 000 deaths in 2008. • 88% of which occur in developing countries: 53 000 in Africa, 31 700 in Latin America and the Caribbean, and 159 800 in Asia.

47. BURDEN OF CANCER (FEMALE) IN INDIA

50. RECOMMENDATIONS • Integrated approach is beneficial specially for women as it covers three cancer at a time under one roof . • High quality Training of screeners. • Appropriate Referral facility available For Diagnosis and Treatment.