Evaluation of Visual Screening in Prevention of Cervical and Oral Cancer in India

Abstract

Kohdunkaulan syöpä ja suusyöpä ovat merkittäviä kansanterveysongelmia Intiassa. Kehitysmaaoloissa länsimaissa yleisesti käytetty kohdunkaulan solunäytteisiin (ns. PAPA-koe) perustuva seulontamenetelmä ei kalleutensa vuoksi tule kyseeseen. Siksi on kehitetty menetelmiä, joissa silmämääräisen tarkastelun perusteella voidaan todeta epäilyttävältä näyttäviä muutoksia kohdunkaulassa ja suun limakalvolla. Nämä menetelmät ovat yksinkertaisia eivätkä vaadi lääkärinkoulutusta seulojilta. Intiassa köyhin väestönosa jää usein kokonaan ilman terveydenhuollon palveluja. Hinnaltaan edulliset seulontamenetelmät ovat todellinen mahdollisuus ehkäistä syöpää tilanteessa, jossa syövän hoito on hintansa vuoksi useimmille ihmisille käytännössä mahdotonta. Silmämääräisen tarkastelun jälkeen kohdunkaulan muutokset hoidetaan yksinkertaisilla menetelmillä saman tien, jolloin varsinkin maaseudun asukkaat saavat hoidon eivätkä jää menemättä uudelle käynnille mahdollisesti kaukaisellekin klinikalle. Tutkimuksen tavoitteena oli selvittää erilaisissa tutkimusasetelmissa useiden eri seulontamenetelmien vaikutusta kohdunkaulan syövän ennalta ehkäisyn keinoina ja selvittää näiden organisoitujen seulontaohjelmien vaikutusta kohdunkaulan syövästä ja suusyövästä aiheutuvaan kuolleisuuteen Intiassa. Tutkimuksissa verrattiin vaikutuksia seulonta- ja vertailuryhmissä. Eri tutkimusryhmien koot vaihtelivat 58 000:n ja 190 000:n henkilön välillä. Tutkimukset suoritettiin Dingdigulissa Tamil Nadun osavaltiossa ja Trivandrumissa, Keralassa. Tutkimustulokset osoittivat, että silmämääräiset seulontamenetelmät toimivat toistettuina ja järjestelmällisesti toteutettuina erinomaisesti kehittyvien maiden olosuhteissa. Kohdunkaulan syövän ilmaantuvuus pieneni 25% ja kuolleisuus peräti 35% yhdessä tutkimusosiossa. Myös suusyövän aiheuttamassa kuolleisuudessa havaittiin 20%:n vähenemä. Asiallisesti järjestettyinä silmämääräisiin menetelmiin perustuvat seulontaohjelmat vaikuttavat kuolleisuutta vähentävästi ja niitä voidaan soveltaa muuallakin kehittyvien maiden olosuhteissa. Tutkimukset koordinoi WHO:n Kansainvälinen syöväntutkimuskeskus (International Agency for Research on Cancer, Lyon, Ranska) yhteistyössä paikallisten intialaisten tutkijoiden kanssa. Tutkimukset rahoitti yhdysvaltalainen Bill ja Melinda Gatesin säätiö. Väitöskirjatyön ohjaajina toimivat tohtori Rengaswamy Sankaranarayanan, Head of Screening Group, Pathogenesis and Prevention Cluster, International Agency for Research on Cancer, Lyon, Ranska ja professori Risto Sankila, Terveystieteen laitos, Tampereen yliopisto ja Suomen Syöpärekisteri, Helsinki.Globally, India has the greatest relative burden of cancers of the cervix and oral cavity in terms of absolute numbers, and numbers of these two cancers summed together form the biggest part of the cancers in the country. With well organized screening programmes, screening for precancerous lesion of these two cancers and giving appropriate treatment to individuals with these lesions, would be beneficial in reducing the number of cancers and cancer deaths in the country. Pap smear, which has been seen to be an effective cervical cancer screening technique in the developed world, is resource demanding, requiring a laboratory infrastructure, quality assurance for the different steps involved and a system to report the test results to women. For this reason, implementation of Pap smear screening in India, as in other low/medium resourced countries, has met challenges and difficulties, leading to the evaluation of alternative, simple, safe, acceptable, affordable and inexpensive visual inspection techniques for detecting cervical precancer lesions and preventing cervical cancer. Furthermore, oral visual inspection is an oral cancer screening method which is cheap, can be easily applied by a wide range of medical personnel and, hence, is suitable for India and other developing countries. The main aim of this study was to assess the validity of these visual inspection techniques and to evaluate what impact they would have on reducing the incidence of and/or mortality from cervical and oral cancers when used in organized screening programmes, especially in low/medium resourced settings. The test performance of five cervical cancer screening methods, visual inspection with acetic acid (VIA), visual inspection with Lugol s iodine (VILI), VIA with magnification (VIAM), conventional Pap smear and Human papilomavirus (HPV) testing, were simultaneously evaluated in more than 58,000 women aged 25 to 64 from eleven urban settings in India (6 centres) and five African countries (5 centres), all centres following the same protocol. These studies were carried out by the International Agency for Research on Cancer (IARC) as part of the Alliance for Cervical Cancer Prevention (ACCP) supported by the Bill & Melinda Gates Foundation (Seattle, Washington, USA) to advance cervical cancer prevention in low/medium resourced countries. The test accuracy of VIA and VILI in detecting high grade cervical disease was found to be similar or even better than that of conventional Pap smear. In order to evaluate whether a single lifetime VIA screening and treatment of detected cervical intraepithelial neoplasia by cryotherapy and excision under field conditions, all provided by trained nurses, can lead to reduced cervical cancer incidence and mortality among women offered screening compared to a similar group of women receiving the existing standard health care, IARC in collaboration with the Christian Fellowship Community Health Centre, a rural hospital and a cancer centre in the Dindigul District of Tamil Nadu State in South India, organized a large randomized controlled trial involving about 80,000 women aged 30-59 years. In this trial, 57 municipal administrative units (49,300 women) were randomly allocated to the intervention group and 56 to the control group (31,000 women). Women (31,300 in number) in the intervention group were then offered VIA, and VIA positive women were colposcopied and/or biopsied by the nurse during the same screening visit followed by immediate treatment with cryotherapy, when appropriate. Women with lesions not eligible for cryotherapy were referred for loop electrosurgical excision procedure (LEEP) and those with suspected invasive cancer were referred for further investigations and treatment. After seven years from the beginning of screening, there was a 25% reduction in the number of cervical cancer cases, and a 35% reduction in the number of cervical cancer deaths among women offered VIA screening compared to those not offered screening. In conclusion, this trial showed that VIA screening could reduce the cervical cancer burden. In a similar randomized oral cancer screening trial, carried out by IARC in collaboration with the Regional Cancer Centre, Trivandrum, Kerala, India, 13 municipal administrative units, involving about 191,800 apparently healthy individuals of 35 years and above, were randomly allocated to two groups. The intervention group (with about 96,500 individuals) received three rounds of oral visual inspection at 3-year intervals provided by trained health workers, whereas the control group received the standard health care. The aim of this trial was to assess if oral visual screening would ultimately lead to a reduction in oral cancer mortality in the intervention group compared to the control group. Nine years from the initiation of screening, a 21% reduction in oral cancer mortality was observed in the intervention group compared to the control group which did not reach statistical significance. However, a statistically significant 33% reduction in mortality was observed among tobacco and/or alcohol users compared to similar control subjects. In summary, evidence from this Indian study shows that oral visual screening can reduce mortality in high-risk individuals. In a nested case-control study using data from the Trivandrum oral cancer screening trial it was shown that individuals chewing paan, smoking bidi and/or drinking alcohol heavily were more likely to catch oral cancer compared to those not having the habits. Big differences in risk estimates among men and women chewing paan were observed with a 3-fold increased risk of oral cancer for male chewers compared to an 11-fold increased risk among female chewers, both groups compared to their corresponding never chewers. Effects of chewing paan with or without tobacco on oral cancer risk were elevated for both sexes. A 2-fold increased risk of oral cancer was observed among male bidi smokers. The risk of catching oral cancer increased with increasing frequency and duration of chewing and alcohol drinking, as well as with increasing duration of bidi smoking. These results further show that cessation of tobacco use and moderation of alcohol use in combination with early diagnosis remain the key elements in oral cancer prevention and control. India, like many low and medium resourced countries, is hit hard by the burden of cervical and oral cancers. It has a limited health budget, cancer treatment facilities are not universally available and life-prolonging therapies are often unavailable. Nevertheless, it is of great importance to prevent those cancers (such as cervical and oral cancer) that can be prevented. Based on the evidence discussed in this dissertation, specific priorities should be given to primary prevention initiatives aimed at taking action against tobacco and heavy alcohol consumption and intensified action against cancers of the cervix and oral cavity through screening

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