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There are no organized or opportunistic screening programs for cervical cancer in any of the high- risk sub-Saharan African countries. While data from Uganda indicate that, at least in some areas of the country, substantial increases in the incidence of cervical cancer may have occurred (13), there is no evidence of an increase in incidence over time in Zimbabwe (42). Studies in Zimbabwe and South Africa have assessed the performance characteristics of potentially alternative screening tests such as visual inspection with acetic acid (VIA) and HPV testing. A cross-sectional screening study in Zimbabwe reported that the sensitivity and specificity to detect high-grade dysplasias and cancer was 77% and 64%, respectively for VIA compared to 43% and 91% for cytology (43). The sensitivity and specificity of HPV testing using Hybrid Capture II assay (Digene Corporation, Gaithersburg, USA) were 81% and 62%, respectively (44); the sensitivity and specificity of HPV testing was, respectively, 91% and 41% for HIV-infected women and 62% and 75%, respectively, for HIV-negative women (45). It is also reported that the sensitivity and specificity of VIA and HPV testing, when used sequentially, was 64% and 82%, respectively (46).

South Africa. The South African Institute of Medical Research organized the infrastructure for mass screening of the female population of Soweto (Project Screen Soweto) so that 90 000 cytology smears could be tested annually (47). However, the lack of a planned population education and motivation program resulted in poor participation of the target population in the program. In a cross- sectional study that addressed the comparative performance of cytology, VIA, cervicography, and HPV testing in South Africa, the sensitivity was found to be 78%, 67%, 53%, and 73%, respectively; the specificity was 94%, 83%, 89%, and 86%, respectively (48). In another study in South Africa, HPV testing using self-collected vaginal samples was found to be more sensitive than cytology (66% versus 61%), but less specific (83% versus 88%) (49). In an earlier study in South Africa, the sensitivity of VIA was found to be 65% (50). A recent study of the cost- effectiveness of several cervical cancer screening strategies, based on the South African experience, indicated that strategies using VIA or HPV DNA testing may offer attractive alternatives to cytology- based screening programmes in low-resource settings (51). When all the strategies were analyzed on the basis of a single lifetime screening at age 35 years compared with no screening, it was found that HPV testing, followed by treatment of screen-positive women at a second visit, cost US$ 39 per year of life saved (27% reduction in cancer incidence); VIA, coupled with immediate treatment of screen-positive women at the first visit, was the next most cost- effective (26% reduction in cancer incidence) and was cost saving; cytology, followed by treatment of screen-positive women at a second visit, was the least effective (19% reduction in cancer incidence) at a cost of US$ 81 per year of life saved (51).

Currently, cytology smears are provided on demand in antenatal, postnatal, gynecology, and family planning clinics in South Africa. Work to develop a cervical screening policy for South Africa, based on the models of natural history, and has been ongoing for some time. It is proposed to initiate screening at the age of 30 years with three smears being carried out in a woman's lifetime. However, there has been debate about both whether this policy should be implemented and how. A pilot project to set up screening services using the health systems development approach is currently being undertaken by three provincial departments of health (Western Cape, Northern Cape, and Gauteng) in cooperation with nongovernmental organizations. This approach seeks to set up programme components such as reaching the target population, providing a competent screening service, relaying the results, and organizing referral, investigation, treatment and follow-up of screening-positive women. It is expected that these tested methods will be applied in the provinces and then nationally.

A three-arm, prospective randomized intervention trial in South Africa is currently addressing the comparative safety, acceptability and efficacy of screening women with VIA and HPV DNA testing and immediately treating screen-positive women with cryotherapy performed by nurses in a primary health care setting. Outcome measures include reduction of high-grade cervical cancer precursors in treated versus untreated women, followed over a 12-month period.

Other countries: Cross-sectional/randomized screening intervention studies are currently ongoing in several African countries ¾ Burkina Faso, Congo (Brazzaville), Ghana, Guinea (Conakry), Kenya, Mali, Niger, and Nigeria ¾ to address the accuracy of various screening approaches such as cytology, HPV testing, VIA, and visual inspection with Lugol's iodine (VILI) as well as the detection rates associated with them.

South Asia

India. India accounts for one-fifth of the world burden of cervical cancer. There are no organized or high-level opportunistic screening programmes for cervical cancer in any of the provincial states. Data from population-based cancer registries in different regions indicate a slow, but steady, decline in the incidence of cervical cancer. However, the rates are still too high, particularly in the rural areas, and the absolute number of cases is on the increase due to population growth. Efforts to improve awareness of the population have resulted in early detection of and improved survival from cervical cancer in a backward rural region in western India (52, 53). Also in two sub districts of western India where the literacy among women is less than 20% there have been attempts to evaluate the role of improved awareness in the early detection and control of cervical cancer (54). Person-to-person and group health education on cervical cancer were provided to 97 000 women in Madha Tehsil, Solapur district, Maharashtra State, in western India; 79 000 women in Karmala Tehsil served as the control population. This program was initiated in 1995 and the preliminary results for 1995-99 indicate that, compared with the control area, in the intervention sub district a substantially higher proportion of women presented with cervical cancer in earlier stages with significantly reduced case fatality (Table 1).

 

 

 

 

 

 

Visual inspection-based approaches to cervical cancer screening have been extensively investigated in India. The performance characteristics of unaided visual inspection (without acetic acid), also known as "downstaging", has been addressed in several studies (55). The unaided approach suffers from low sensitivity and specificity to detect cervical dysplasia  Currently there are several ongoing, cross-sectional studies being carried out on other screening approaches such as VIA, VIA with magnification (VIAM), and HPV testing as alternative screening approaches. Results from two reported studies indicate that the sensitivity of VIA to detect high-grade lesions was similar or higher than that of conventional cytology but that its specificity was lower (56,57).

There are three large, ongoing cluster-randomized intervention trials in India ¾ in Dindigul district (Tamil Nadu), in Mumbai, and in Osmanabad district (Maharashtra) ¾ to evaluate the effectiveness of VIA, in reducing cervical cancer incidence and mortality. The intervention programme in Osmanabad district aims to address the comparative efficacy and cost-effectiveness of three different primary screening approaches in reducing the incidence and mortality: VIA, conventional cervical cytology, and HPV testing. The results of these studies are likely to provide valuable leads to the development of public health policies to control cervical cancer in developing countries. A recently held national workshop on control of cervical cancer in India reviewed the various methodologies for the early detection of cervical neoplasia and considered both good quality conventional cytology and VIA as suitable tests for early clinical diagnosis (58-62). In view of the inadequately developed cytology services, VIA was recommended as the immediate option for the introduction of cervical cancer control initiatives as part of the district cancer control programs in 54 districts in India.

 

South-east Asia

In Singapore, a high level of opportunistic screening for cervical cancer has been operating over the last few years, but has had only minimal impact on the overall incidence and mortality from cervical cancer (12). However, a substantial decline in cervical cancer incidence and mortality has been observed among the Singapore Indian community, with stable trends among the Chinese and Malay communities. Efforts are currently underway to provide an organized screening program by restructuring the existing opportunistic program. A test-and-treat approach following VIA is currently being evaluated in Thailand. A cytology-based demonstration program on screening is currently being implemented by the MOH in Nakornpanam Province in north-east Thailand. The comparative performance of VIA and VILI in detecting cervical neoplasia is being addressed in Vientiane, Lao People's Democratic Republic. Ongoing studies in rural China are addressing the accuracy of cytology and non- cytology-based screening approaches.

 Situation in Uganda:

From the Ugandan experience, cervical cancer is the commonest malignancy among women (13).  Over 80% of patients diagnosed with cancer at Mulago hospital present with advanced disease (63, 64). Cancer cervix patients on palliative radiotherapy account for ~20 to 30% of the patients on the gynecological wards at Mulago hospital. There are no organized screening programs in Uganda, same as in most of the developing countries. The only available activity has been to use opportunistic screening of those women who come to health units for other reasons. Screening of women becomes a responsibility of medical workers who should have the necessary skills and should have functional units to be able to perform cervical screening (63). From a study conducted at Mulago, the authors noted that knowledge about risks for cervical cancers was low among finalists in nursing and medical schools (40 %), but 93% considered it a Public health problem. Most of those final students did not feel confident enough to perform a pap smear (63). Recent research work from a population survey in Uganda on Predictors of High Risk papilloma Virus showed that ~17% of the studied women had high risk HPV types (self collected vaginal samples wee used). Presence of HIV infection was highly associated with HPV. This shows that high risk HPV is highly prevent in Uganda and yet screening services are still poor (65).

Way Forward:

Effective screening programs in developing countries:

To organize effective cervical cancer screening programs, developing countries will have to;

 -find adequate financial resources, develop the infrastructure, train the needed manpower, and elaborate surveillance mechanisms for screening, investigating, treating, and follow-up of the targeted women.

- There is considerable discussion focused on which screening test to use ¾ cytology or alternatives to cytology, such as VIA or HPV testing ¾ or which combinations/sequence of screening tests should be used for screening in developing countries. Choosing a suitable screening test is only one aspect of a screening program.

- A more fundamental and challenging issue is the organization of the program in its totality. Whichever screening test is to be used, the challenges in organizing a screening program are more or less the same.

- However, screening tests (e.g. cytology, HPV testing) that require additional recalls and revisits for diagnostic evaluation and treatment may pose added logistic difficulties and these may emerge as another barrier for participation in low-resource settings.

-The choice of screening test in countries/ regions that plan to initiate new programs should be based on the comparative performance characteristics of cytology and its potential alternatives such as VIA, their relative costs, technical requirements, the level of development of laboratory infrastructure, and the feasibility in a given country/region.

-A highly sensitive test should be provided. If cytology is chosen, considerable attention should be given to obtaining good quality smears, staining, and reporting so that a moderately high sensitivity to detect lesions is ensured.

- If VIA is chosen for screening, considerable attention should be given to the proper monitoring and evaluation of the program inputs and outcomes before further expansion, since VIA is still an experimental option for cervical cancer screening and it remains to be demonstrated whether VIA-based screening programs are associated with a reduction in cervical cancer incidence and mortality.

- In developing countries, existing ineffective cytology- based programs should be urgently reorganized and monitored.

Quantitative studies have shown that after two or more negative cytology smears, even screening once every 10 years yields a 64% reduction in the incidence of invasive cervical cancer, assuming 100% compliance (15, 59). Further studies based on this model indicate that once-in-a-lifetime screening may yield around 25-30% reduction in the incidence of cervical cancer (60, 61,).

To have an impact on cervical cancer incidence and mortality, efforts must be focused on the following:

1)      Increasing the awareness of women about cervical cancer and preventive health-seeking behavior; screening all women aged 35¾50 years at least once, before expanding the services and providing repeated screening (11). In South Africa, it’s proposed that cancer cervix screening should start at 30 yrs, with 3 pap smears to be done in a woman’s life. (Age of onset of screening is still a controversy). Person to person and group health education on cancer cervix can attract people to go for screening as long as the infrastructure is functional.

2)       Providing a screening test with high sensitivity (since women have less frequent opportunities for repeated screening);

3)      Treating women with high-grade dysplasia and cancer;

4)      Monitoring program inputs and evaluating the outcomes should part of the package.

5)      Strengthening training of service providers on how to perform cancer cervix screening is mandatory plus to training cytopathologists and cytotechnicians to ensure quality specimens and interpretation of results.

 

 

 

References:

 

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11)     Rengaswamy Sankaranayanan, Atul Madhukur Budukh, and Rajamanickam Rajkumar. Effective screening programmes for cervical cancer in low and income developing countries. (Bulletin of the World Health Organization vol.79 n.10 Genebra 2001).

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                  (Lyon, International Agency for Research on cancer,      1995 (IARC scientific Publications No.121).

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                 British Journal of Cancer, 2000, 82: 585-1592.

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              Agency for Research on Cancer, 1986 (IARC Scientific Publications No. 76).

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20) Smith JS, Green J, de Gonzalez A, et al. Cervical cancer and use of hormonal contraceptives. a systematic review. Lancet 2003: 361: 1159-67.

21) Hildesheim A, Herrero R, Castle PE, Wacholder S, Bratti MC, Sherman ME, Lorinez AT, Burk RD, Morales J et al. HPV co-factors related to the development of cervical cancer: Results from a population based study in Costa Rica. Br J cancer.2001 may 4; 84(9):1219-26.

22) Horng JT, Hu KC. Wu LC, Huang HD, Lin FM, Huang SL, Lai HC, Chu TY. Identifying the combination of genetic factors that determine susceptibility to cervical cancer. IEEE Trans inf Technol Biomed.2004 Mar;8(1):59-66.

23) Hermandez BY, McDuffie K, Wilkens LR, Kamemoto L, Goodman MT. Diet and pre-malignant lesions of the cervix: Evidence of a protective role for folate, riboflavin, thiamin and vitamin B12.Cancer Causes Control. 2003 Nov; 14(9):859-70.

24) Clifford GM, Polesel J, Rickenbach M, Dal Maso L, Keiser O, Kofler A, Rapiti E et al. cancer risk in the Swiss HIV Cohort study: associations with immunodeficiency, smoking and highly active antiretroviral therapy. J Natl Cancer Inst.2005 Mar 16;97(6):425-32.

25) Hellberg D, Valentin J, Nilsson S. Smoking and cervical intra-epithelial neoplasia. Is it an association independent of sexual and other risk factors? Acta Obstet Gynecol scand. 1986;65(6):625-31.

26) Smith JS, Herrero R, Bosetti C, Bosch FX, Eluf-Neto J, Castellsague X, Meijer CJ Van den Brule AJ, Franceshi S, Ashley R. International Agency for research on Cancer (IARC). Multi Centric Cervical cancer study Group. Herpes simplex virus-2 as a human papillomavirus cofactor in the etiology of invasive cervical cancer J Natl Cancer.Inst.2002 Nov 6; 94(21):1604-13.

27)Schmauz R, Okong P, de Villiers EM, Dennin R, Brade L, Lwanga SK, Owor r. Multiple infections in cases of cervical cancer from a high incidence area in tropical Africa. Int J Cancer. 1989 May 15;43(5)805-9.

28) Nasiell K et al. Behaviour of mild dysplasia during long-term follow-up. Obstetrics and Gynaecology, 1986, 67: 665¾669.

29) Holowaty P et al. Natural history of dysplasia of the uterine cervix. Journal of the National Cancer Institute, 1999, 91:  252-268.     [ Medline ]

30) Fahey MT et al. Meta-analysis of Pap test accuracy. American Journal of Epidemiology, 1995, 141: 680¾689. [ Medline ]

31) Nanda K et al. Accuracy of the Papanicolaou test in screening for and follow-up of cervical cytologic abnormalities: a systematic review. Annals of Internal Medicine, 2000, 132: 810¾819. [ Medline ]

32) Herdman C et al. Planning appropriate cervical cancer prevention programs. Seattle, WA, Program for Appropriate Technology in Health, 2000.

33) Irwin IR et al. Screening practices for cervical and breast cancer in Costa Rica. Bulletin of the Pan American Health Organization, 1991, 25: 16¾26. [ Medline ]

34) Herrero R et al. Determinants of geographical variations of cervical cancer in Costa Rica. Bulletin of the Pan American Health Organization, 1993, 27: 15¾25.

35) Sierra R et al. Cancer in Costa Rica. Lyon, International Agency for Research on Cancer, 1988 (IARC Technical Report No. 1).

36) Schiffman et al. HPV DNA testing in cervical cancer screening: results from women in high-risk province of Costa Rica. Journal of the American Medical Association, 2000, 283: 87¾93. [ Medline ]

37) Fernandez Garrotte L. Evaluation of the Cervical Cancer Control Program in Cuba. Bulletin of the Pan American Health Organization, 1996, 30, 387¾391.  [ Medline ]

38) Lazcano-Ponce EC et al. Evaluation model of the Mexican national program for early cervical cancer detection and proposals for a new approach. Cancer Causes Control, 1998, 9: 241¾ 251. [ Medline ]

39) Lazcano-Ponce EC et al. Cervical cancer screening in developing countries: Why is it ineffective? The case of Mexico. Archives of Medical Research, 1999, 30: 240¾250. [ Lilacs ]

40) Lazcano-Ponce EC et al. Validity and reproducibility of cytologic diagnosis in a sample of cervical cancer screening centers in Mexico. Acta Cytologica, 1997, 41: 277¾284. [ Medline ]

41) Lazcano-Ponce EC et al. Mortality from cervical carcinoma in Mexico: impact of screening, 1980¾1990. Acta Cytologica, 1996, 40: 506¾512. [ Medline ]

42) Chokunonga E et al. Cancer incidence in the African population of Harare, Zimbabwe: second results from the cancer registry 1993¾1995. International Journal of Cancer, 2000, 85: 54¾ 59. [ Medline ]

43) University of Zimbabwe/JHPIEGO Cervical cancer prevention project. Visual inspection with acetic acid for cervical cancer screening: test qualities in a primary-care setting. Lancet, 1999, 353: 869¾873.

44) Womack SD et al. Evaluation of human papillomavirus assay in cervical screening in Zimbabwe. British Journal of Obstetrics and Gynaecology, 2000, 107: 33¾38.

45) Womack SD et al. HPV-based cervical cancer screening in a population at high risk for HIV infection. International Journal of Cancer, 2000, 85: 206¾210.  [ Medline ]

46) Blumenthal PD et al. Adjunctive testing for cervical cancer in low- resource settings with visual inspection, HPV, and the Pap smear. International Journal of Gynecology and Obstetrics, 2001, 72: 47¾53. [ Medline ]

47) Leiman G. "Project Screen Soweto" ¾ a planned cervical screening programme in a high-risk population. South African Medical Journal, 1987, 2: 61¾68.

48) Denny et al. Evaluation of alternative methods of cervical cancer screening for resource-poor settings. Cancer, 2000, 89: 826¾ 833. [ Medline ]

49) Wright TC et al. HPV DNA testing of self-collected vaginal samples compared with cytologic screening to detect cervical cancer. Journal of the American Medical Association, 2000, 283: 81¾86. [ Medline ]

50)  Megevand E et al. Acetic acid visualization of the cervix: an alternative to cytologic screening. Obstetrics and Gynecology, 1996, 88: 383¾386. [ Medline ]

51) Goldie SJ et al. Policy analysis of cervical cancer screening strategies in low-resource settings. Clinical benefits and cost effectiveness. Journal of the American Medical Association, 2001, 285: 3107¾3115.  [ Medline ]

52) Jayant K et al. Improved stage at diagnosis of cervical cancer with increased cancer awareness in a rural Indian population. International Journal of Cancer, 1995, 63: 161¾163. [ Medline ]

53) Jayant K et al. Survival from cancer in Barshi registry, rural India. In: Sankaranarayanan R, Black RJ, Parkin DM, eds. Cancer survival in developing countries. Lyon, International Agency for Research on Cancer, 1988: 69¾77 (IARC Scientific Publications No. 145).

54) Parkin DM, Sankaranarayanan R. Prevention of cervical cancer in developing countries. Thai Journal of Obstetrics and Gynaecology, 1999, 11S: 3¾20.

55) Sankaranarayanan R et al. Visual inspection as a screening test for cervical cancer control in developing countries. In: Franco E, Monsonego J, eds. New developments in cervical cancer screening and prevention. Oxford, Blackwell Science, 1997: 411¾421.

56) Sankaranarayanan R et al. Performance of visual inspection after acetic acid application (VIA) in the detection of cervical cancer precursors. Cancer, 1998, 83: 2150¾2156.

57) Sankaranarayanan R et al. Visual inspection with acetic acid in the early detection of cervical cancer and precursors. International Journal of Cancer, 1999, 80: 161¾163. [ Medline ]

58) National workshop on control of cervical cancer- alternative strategies. New Delhi, Institute of Cytology and Preventive Oncology, Indian Council of Medical Research, 2001.

 59) Hakama M et al., eds. Screening for cancer of the uterine cervix: Lyon, International Agency for Research on Cancer, 1986 (IARC Scientific Publications No. 76).

60) Prabhakar AK. Cervical cancer in India strategy for control: Indian Journal of Cancer, 1992, 104: 29¾32.

61) Murthy NS et al. Estimation of reduction in life-time risk of cervical cancer through one life-time screening. Neoplasma, 1993, 40: 255¾258.  [ Medline ]

62) Miller AB. Cervical cancer screening programmes - Managerial guidelines. Geneva, World Health Organization, 1992.

63) Twaha Mutyaba 1, Francis A Miiro 1, and Elisabete Weiderpass 2,3. Knowledge, attitudes and practices on cancer screening among the medical workers of Mulago Hospital, Uganda.

64) Mirembe F (1993): The changing pattern of carcinoma of cervix in Uganda. Proceedings of the Scientific Conference of the Associations of the Associations of Obstetricians and Gynaecologists of Uganda:

65) Asiimwe Stephen (2006): Predictors of High Risk Human Papilloma Virus (HPV) Infection: A Population Based Survey in Rural Uganda. (Research work for his Ms-Epidemiology, 2006).

More information can be obtained from the following websites:

1) http://www.ahrq.gov/clinic/uspstf/uspscerv.html.

U.S. Preventive Services Task Force: Screening for Cervical cancer:

Release Date: January 2003 (Summary of Recommendations / Supporting Documents)

2)http://www.sciencedaily.com/releases/2004/1/041123162300.html

 HPV Vaccine Studied For First Time In Men:Source: Medical College of Georgia (Posted November 2004

3) Cancer screening web sit.htm. (bbc.co.uk) BBC Health Condition Screening Programmes.

4) Health Promotion Lifestyle. (http://www.patient.co.uk/showdoc/16/#can.

5)New scientist.com .Will the cancer Vaccine get to al lwomen? http://www.newscientist.com/channel/sex/mg18624954.500.

 6)Websiteteforsymptomsfrocancerofthecervix.(http://www.wrongdiagnosis.com/c/cervical_cancer/symptoms.htm)

7)http://www.fpahealth.org.au/news/20021128_papvirus.html: Human Papilloma Virus(HPV) Vaccine.

8)The interested reader is referred to common text books about details of examination of a patient with cancer of the cervix and for details about staging of the cancer and management).

à) Cervical Cancer and Preinvasive Neoplasia (Hardcover)
by Stephen C., M.D. Rubin (Editor), William J. Hoskins (Editor)

à) Clinical Gynecologic Oncology (Hardcover)
by Philip J. Disaia, William T. Creasman

à Te Linde's Operative Gynecology (Hardcover)
by Howard W. Jones (Editor), John A. Rock (Editor), Richard W. Te Linde (Editor)

 

 NB To read about Programmes that have worked: Most of the section on Cervical Cancer Screening from developing countries is from a “WHO Bulletin” where I found good information regarding experience from developing countries”.

 

 

 

 

 

     

 

 

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