Colposcopy is not necessary to assess the risk to the cervix in HIV-positive women: An international cohort study of cervical pathology in HIV-1 positive women Henry Kitchener 1 * , Linsey Nelson 1 , Joanna Adams 2 , David Mesher 2 , Peter Sasieni 2 , Heather Cubie 3 , Catherine Moore 3 , Isabelle Heard 4 , Alberto Agarossi 5 , Elena Casolati 5 , Lynette Denny 6 , Caroline Bradbeer 7 , Fiona Lyons 8 , Gerry Beattie 9 and Tomasz Niemiec 10 1 Academic Unit of Obstetrics and Gynaecology, University of Manchester, St. Mary’s Hospital, Manchester, United Kingdom 2 Cancer Research, Department of Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventive Medicine, London, United Kingdom 3 Specialist Virology Centre, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom 4 Unit  e de Biologie de la Reproduction, Hoˆpital Piti  e-Salp etrie`re, Paris, France 5 Department of Obstetrics and Gynaecology, L. SACCO Hospital, University of Milan, Milan, Italy 6 Department of Obstetrics and Gynaecology, University of Cape Town, South Africa 7 Department of GU Medicine, St Thomas’s Hospital, London, United Kingdom 8 Department of GU Medicine, Saint James Hospital, Dublin, Ireland 9 Department of Obstetrics and Gynaecology, West Lothian Healthcare NHS Trust St. John’s Hospital, Livingston, West Lothian, Scotland 10 Department of Obstetrics and Gynecology, Research Institute of Mother and Child, Warsaw, Poland The objectives of this prospective multicentre international cohort study are to describe the characteristics of a cohort of HIV-1 posi- tive women and determine the best management system by com- paring cervical pathology according to results of cytology, colpo- scopy and human papillomavirus (HPV) testing at baseline and throughout follow-up. A. Cohorts of known HIV-positive women were recruited from 6 hospital-based European centres and a community-based South African centre. Following registration, women were reviewed every 6 months to undergo cervical surveil- lance including cytology, colposcopy, histopathology and HPV testing, using the HPV hybrid capture assay. Independent risk fac- tors for the incidence of cytological abnormality and acquisition/ clearance of HPV infection during follow up were identified. A total of 1,534 women were recruited, 400 of which were from South Africa. At baseline, among European women, 66% had nor- mal cytology and half were HPV negative and among South Afri- can women, 45% had normal cytology and one third (32%) were HPV negative. The sensitivity of cytology (ASCUS) matched with that of colposcopy to detect CIN21. Rate of detection of high grade CIN at 2 years was similar in European and South African women (11 and 9.3%, respectively). Cytology and HPV testing alone were each sufficiently sensitive as a screening test at 2 yearly intervals. Our data confirm the high prevalence of low-grade cyto- logical abnormalities and high-risk HPV infection. Cytology appears to be sufficient for cervical surveillance, with HPV testing being less specific with poor positive predictive value. There appears to be no additional benefit from routine colposcopy. ' 2007 Wiley-Liss, Inc. Key words: HIV; cervical; pathology; screening; diagnosis It is now widely acknowledged that human papillomavirus (HPV) infection is an essential factor in the development of cervi- cal intraepithelial neoplasia (CIN) and cancer of the cervix. It has also become clear that HIV-positive women carry an increased risk of persistent genital HPV infection and therefore have an increased risk of HPV-associated lower genital tract neoplasia, particularly CIN. Higher incidence and prevalence of CIN have been reported in HIV-1 positive women. 1–5 The HIV/AIDS pandemic continues to spread unabated in many parts of the world and there is now an increasing number of HIV- infected women in European countries largely due to increased heter- osexual transmission (UNAIDS report, Dec. 2004, www.unaids.org). Significant progress has been made in the development of antiretro- viral therapy (HAART), with 23 at last count licensed antiretroviral drugs now in use that target HIV replication. With the advent and widespread use of combination HAART, AIDS-associated mortality and morbidity have fallen dramatically in industrialized countries. 6,7 In developed healthcare systems where combination HAART is available, the prospect for long-term survival from HIV/AIDS has been demonstrated and consequently preventive health care strat- egies become relevant. For HIV infected women, this means consid- eration of the risk to the cervix. In resource-poor healthcare settings the nonavailability of combination HAART means that women are at risk of dying early from AIDS and, although the risk of cervical cancer is significantly increased, death from opportunistic infections is likely to precede cervical pathology. 8 At present, there is no clear consensus as how best to prevent and manage cervical disease in HIV-positive women. This is in part due to the lack of reliable information regarding the clinical effective- ness of cytology, colposcopy and HPV testing in HIV infected women. 9,10 Furthermore much of the work that has been done to date precedes the widespread use of combination HAART and the impact of this on the natural history of cervical disease in HIV infected women is still debated. 11 There are also wide differences in HIV-infected cohorts in their ethnicity and behavioural character- istics that may influence outcomes in published studies. This inter- national prospective study sought to determine the risks to the cer- vix in HIV infected women, in a European cohort with access to combination HAART as well as a cohort from South Africa without access to combination HAART. The overall aim of the project was to develop an evidence base with which clinical guidelines regard- ing cervical surveillance and management could be developed. Methods Clinical protocol Seven centres involving specialist clinics responsible for the gynaecological management of women with HIV formed a collab- The authors belong to the MACH-1 Group. H. Kitchener, I. Heard, E. Casolati and H. Cubie constitute the Writing Committee. Grant sponsors: Parthenon Trust; Secure the Future (Bristol-Myers Squibb, Cape Town); 3M Pharmaceuticals. *Correspondence to: Academic Unit of Obstetrics and Gynaecology, St. Mary’s Hospital, Manchester M13 0JH, UK. Fax: 144-161-276-6134. E-mail: henry.kitchener@cmmc.nhs.uk Received 6 December 2006; Accepted after revision 3 April 2007 DOI 10.1002/ijc.22947 Published online 7 August 2007 in Wiley InterScience (www.interscience. wiley.com). Int. J. Cancer: 121, 2484–2491 (2007) ' 2007 Wiley-Liss, Inc. Publication of the International Union Against Cancer