Strategies for Control of Cervical Cancer in India Dr. Kishore Chaudhry Deputy Director General (Sr. Grade) Indian Council of Medical Research New Delhi 6th INCTR Annual Meeting Chennai, India 10-13 December 2005
DELHI SIKKIM DIBRUGARH GUWAHATI SILCHAR IMPHAL MIZORAM KOLKATTA BHOPAL MUMBAI BARSHI ICMR HEAD QUARTERS CHENNAI NCRP COORDINATING UNIT BANGALORE POPULATION BASED REGISTRY POPULATION BASED RURAL REGISTRY HOSPITAL BASED REGISTRY THIRUVANANTHAPURAM MONITORING UNIT OF NERCR NATIONAL CANCER REGISTRY PROGRAMME (Indian Council of Medical Research) • 14 Population Based • 5 Hospital Based AHMEDABAD
Cancer Incidence in Population Based Cancer Registries under NCRP (ICMR), 1999-2000 Males Females
CERVIX UTERI (ICD 10 : C53) Source: Development of an Atlas of Cancer in India First All India Report 2001-2002. NCRP, Bangalore International Comparisons of AAR with that of PBCRs under NCRP
50 40 Bangalore 30 Barshi Bhopal Chennai 20 Delhi Mumbai 10 0 1982 2001 Year CANCER CERVIX Trends in AAR – All Age Groups
Minimum AAR CERVIX UTERI (ICD 10 : C53) Cancer Atlas Project 2001-02 Comparison with PBCRs of NCRP Source: Development of an Atlas of Cancer in India First All India Report 2001-2002. NCRP, Bangalore Mumbai – PBCR : 15.4 Remaining No. of Districts > MAAR of any PBCR :17
Minimum AAR CERVIX UTERI (ICD 10 : C53) Cancer Atlas Project 2001-02 Aizawl (30.1) Mamit (29.6) Thiruvallur (28.6) Villupuram (31.1) Pondicherry (39.2) Cuddalore (29.9)
THIRUVALLUR (28.6) VILLUPURAM (31.1) THIRUVALLUR (2.1) PONDICHERRY (39.2) CUDDALORE (29.9) KANCHEEPURAM (1.9) ERODE (2.0) VILLUPURAM (3.1) PONDICHERRY (3.0) CUDDALORE (2.2) KARAIKAL(1.9) PERAMBALUR(2.1) Districtwise Minimum Age adjusted Incidence Rates per 100,000 Cervix & Penis (ICD-10 : C60) 2001 – 2002, Tamil Nadu TAMILNADU STATE CANCER PENIS CANCER CERVIX
Estimated Number of Incident Cancers in India, 2001 Source: ICMR. Bieenial report of National Cancer Registry Programme, 1988-1989.
Infection with Human Papillomavirus (HPV) Multiple sexual partners/ Promiscuity Early age at consummation of marriage Sexual / Genital hygiene Number of pregnancy Smoking Aetiology of Cervical CancerMajor Risk Factors
HPV and Cervical Cancer • Almost 100% cervical carcinomas are infected with high risk HPVs. • HPV type 16 most predominant (60 to 90%) worldwide, including India. • High risk HPV infected pre-cancers show high rate of progression. • High risk HPV (16/18) can immortalize human squamous epithelial cells invitro. • Systemic immunization with HPV-VLP vaccine can confer protection against HPV infection in animal model.
STAGES DURING CERVICAL CARCINOGENESIS NORMAL CERVICAL EPITHELIUM MILD DYSPLASIA MODERATE DYSPLASIA SEVERE DYSPLASIA CARCINOMA IN SITU MICROINVASIVE CANCER INVASIVE CANCER PRECANCER EARLY CANCER CANCER CERVICAL CANCER IS CURABLE IF DETECTED EARLY 10-15 years
National Cancer Control Programme (NCCP) • Rao Committee (1965) & Wahi Committee (1971) laid down the framework of the Cancer Research and Treatment Programme, which was initiated in 1975. • NCCP initiated in 1984. Updated in 1995 • Objectives • Primary prevention of cancer, particularly tobacco related cancers • Early diagnosis and treatment of cancers (cervix, breast & oropharynx) • Extension and strengthening of therapeutic services, including pain relief.
Treatment Vs Prevention in Cancer Control Programme • Adequate facilities for early detection and treatment may prevent mortality, but would not help in reduction of disease occurrence. Without preventive programmes treatment facilities would require periodic updating and enhancement • Preventive programmes are also not expected to function optimally if they are not backed by effective curative facilities.
Screening Screening is the presumptive identification of unrecognized disease or defects by means of tests, examination, or other procedures that can be applied rapidly Source: WHO. NCCP, 1995 Screening is not necessarily pathognomonic Screening is not a diagnostic tool. It is a public health tool to detect the disease at asymptomatic stage. It is not a method of primary prevention. Early Detection Vs Screening
Proportion of cases belonging to the high-risk group out of all cases in the target population, by percentage of the high-risk group out of total target population and by relative risk (high vs. low risk) Source: Hakama M. Planning and designing of screening programmes. In: Sankila R, démaret E, Hakama m, et al (eds.). Evaluation and monitoring of screening programmes. European Commission, Brussels-Luxembourg, 2000: pp 13-28
Reduction in the cumulative rate of invasive cervical cancer for women aged 35-64 years, with different frequency of screening Assuming 100% compliance & highly Sensitive test Assuming 80% compliance & reduced Sensitive in practice
Disease should be an important public health problem Must have a latent asymptomatic stage Adequate treatment should be available The test should be safe and relatively in-expansive Capable of rapid application Should be accurate and reproducible Test should be acceptable to people The test should be reasonably inexpensive Adequate follow up of the positives should be ensured Involves expenditure to individuals and health services Undesired harm due to screening should be avoided Criteria for Screening
Infrastructure for screening Target population (Age). Identify, reach, invite and screen all. Frequency of Test Tests by whom Training. Equipment. Facilities for sterilization. Location for the test Establishment of cytological laboratory. Staff, equipment. Health education of the target population Transportation of test material & frequency of transportation Quality control of test delivery and test examination Provision of report (modality, time lag) Mechanism of referral (Clear policy, treatment facility, follow up, and prompt treatment) Records Evaluation Elements of Screening
Organized Vs Unorganized Screening • Organized screening refers to active planning in term of call-recall of specified target group according to a pre-decided screening frequency. • Organized screening programmes can be evaluated reliably & in detail. • Wherever comparisons have been possible, organized screening programmes have shown larger effects. • Without active planning, there is a danger of high cost, due to lack of inbuilt mechanisms. • Spontaneous screening is likely to pay greatest attention to high sensitivity without considering its effect on specificity. • Opportunistic screening or camps possibly may maintain the skill in carrying out screening activities. • However, as such they do not help in appreciable reduction of incidence or mortality • However, as a part of organized screening programmes, these could be useful, provided they provide the data to a centralized agency
Pap Smear Screening Visual Inspection of Cervix Visual Inspection of Cervix after magnification Visual Inspection of Cervix after acetic acid, lugol’s iodine HPV detection Regardless of method of Screening, it is important to established and run an efficient network for this purpose. Modalities for Screening for Cervical Cancer
Operational research studies by ICMR showed that it is possible to train para-medical workers on Examination of cervix Collection of Pap smears Pap smears collected under field conditions are adequate Screening for Cervical Cancer
Community Prevalence of HPV in India • Community prevalence of HPV between 6.1% to 10%. • Most infections by HPV 16 or 18. Trivandrum Semiurban MAMC & ICPO study on 446 women in urban slum, Delhi • ICPO’s community based study on 2073 married women at Alipur Delhi (1985-1993) • The prevalence of HPV 16/18 = 10% • The peak rate of prevalence age group 25-29 years
Frequency of HPV in Cervical Cancer Tissues (Hospital based studies) 14.28% 73% 54% 66% 57.5% 56.25% 67% 58.0% 50.0% 88% 42% Gopalkishna etal, 2000 • Exclusive incidence (90%) of HPV type 16 in India. Other major type is HPV 18.
Advantages of HPV Vaccination in Control of Cervical Cancer • Known effective measures for control of cervical cancer aim at early diagnosis (at a pre-cancerous stage or early cancerous stage). Thus, these measures do not prevent occurrence of cervical cancer. • Limited effect of other measures of primary prevention • HPV vaccination aims at prevention rather than early diagnosis. • Vaccination is an accepted mode of disease prevention by community. • It is expected to be cost-effective measure for prevention of cervical cancer.
Approaches for HPV Vaccine • PROPHYLACTIC VACCINE • To be given before onset of HPV infection • THERAPEUTIC VACCINE • Immune response to clear already established HPVinfection.
WHO-ICMR Workshop on HPV Vaccine as a tool for Prevention of Cervical Cancer, New Delhi, September 2002 • Recommendations • There is a need for clinical evaluation of vaccines against HPV for prevention of cervical cancer. • There is meagre data on incidence and transmission dynamics of HPV in the community. A carefully designed vaccine trial could generate it cost-effectively. • Several laboratories engaged in HPV work, but standardization and quality control procedures need to be strengthened. Therapeutic facilities need to be optimized. • Social and behavioural research needs to be undertaken to understand the acceptability or resistance of population towards vaccination. Care should be taken to avoid stigmatization or discrimination of the participants.
WHO-ICMR Workshop on HPV Vaccine as a tool for Prevention of Cervical Cancer New Delhi, September 02 • Recommendations (cont.) • Selection of study population should be based on the principle of selecting those with low probability of HPV infection at enrolment but high probability of getting infected within a short period after vaccination. • Priority should be given to trials in women but trials of vaccination among men may be necessary at a later stage. • Since vaccination programmes are not imminent at this stage, only ethical and gender issues that are relevant to the conduct of clinical trials need to be considered at this stage. • Cost-effectiveness and financial sustainability are extremely important. Currently data is inadequate to optimally address the issue. Trials may provide opportunity to address it. • The trial should preferably be multi-centre and the selection of trial sites should be based on objective assessment and site visits.
HPV Vaccine in Control of Cervical Cancer • Two types of HPV Vaccines have been developed • Prophylactic vaccines, designed to prevent HPV infection • Therapeutic vaccines to prevent development of invasive cancer among HPV positive women. • Four vaccines against high risk HPV are undergoing clinical trials (Manufacture by Merck, Glaxo Smith Kline, NCI & Medigene) • Clinical trials by Merck and GSK have reached phase 3. • HPV vaccine shows potential for control of cervical cancer.
Strengths in India on Control of Cervical Cancer Studies on Visual Inspection of Cervix Condyloma of the anterior lip of cervix Aceto-white epithelial layer showing presence of HPV lesion Cells showing koilocytic changes suggestive of condyloma
Strengths in India on Control of Cervical Cancer Laboratory Strength In situ hybridization with 3H-labeled HPV-16 DNA probe HPV 16 by URR primer Southern Blot Hybridization HPV-16 integration sites
“PAPER-SMEAR” Method developed by ICPO for DRY collection, transport and storage of cervical cytologic specimens for rapid screening of HPV infection by PCR.
Magnavisualizer – Magnification device developed by ICPO is under patenting
Screening for cervical cancer initiated in three districts of Himachal Pradesh (Mandi, Hamirpur, Bilaspur) As a part of package for early detection of cancers of cervix, breast and oral cavity Pap smear once in three years for all women above 30 years Commitment of the State Government to provide recurring funds after five years ensures long-term sustainability Screening for Cervical Cancer