RISK OF INVASIVE CERVICAL CANCER AMONG WOMEN WITH, OR AT RISK FOR, HIV INFECTION Diego SERRAINO 1 *, Patrizia CARRIERI 2 , Christian PRADIER 3 , Ettore BIDOLI 1 , Maria DORRUCCI 4 , Elisa GHETTI 5 , Antonella SCHIESARI 5 , Roberta ZUCCONI 5 , Patrizio PEZZOTTI 4 , Pierre DELLAMONICA 3 , Silvia FRANCESCHI 1 and Giovanni REZZA 4 1 Epidemiology Unit, IRCCS Centro di Riferimento Oncologico, Aviano, Italy 2 INSERM U379, Marseilles, France 3 CISIH–University Hospital, Nice, France 4 Centro Operativo AIDS, Istituto Superiore di Sanita ` , Rome, Italy 5 Centro Medico, Comunita ` di San Patrignano, Rimini, Italy Although invasive cervical cancer (ICC) has been included among the AIDS-defining conditions since 1993, it remains controversial whether HIV infection increases the risk of developing such neoplasm. In this study, ICC risk was longitu- dinally investigated among 1,340 HIV-positive intravenous drug user (IDU ), 811 H IV-negative IDU , and 801 H IV-positive heterosexual women. These women, aged 15–49 years, were followed up at the Italian HIV Seroconverter Study, at the San Patrignano Community (Rimini, North Italy), and in South-eastern France (the DMI-2 study). The number of observed cases of ICC was compared with the expected one, based on ICC incidence rates among women of the same age in the general population of Italy or France, and standardized incidence ratios (SIR) were computed; 9,070 person-years of observation were accumulated among HIV-positive women and 2,310 among HIV-negative ones. Ten cases of ICC were diagnosed among H IV-positive women (SIR  12.8): ICC risk was apparently higher among HIV-positive IDU (SIR  16.7) than among heterosexual women (SIR  6.7). No cases of ICC were diagnosed among H IV-negative IDU women admit- ted to the San Patrignano Community (0.15 cases were expected). Our findings confirm previous suggestions show- ing an increased risk of ICC among HIV-infected women and have important implications at the individual and public health levels. Int. J. Cancer 82:334–337, 1999.  1999 Wiley-Liss, Inc. The AIDS epidemic is increasingly affecting European women, particularly in the South, where yearly AIDS incidence rates nearly doubled between 1991 and 1995 (Franceschi et al., 1998b), and where Italy and France account for nearly 50% of female cases (European Centre for the Epidemiological Monitoring of AIDS, 1998). The growth of AIDS among European women paralleled that observed in the United States, and has been minimally influenced by the inclusion, in 1993, of invasive cervical cancer (ICC) among the AIDS-defining diseases (European Centre for the Epidemiological Monitoring of AIDS, 1998). Several studies have documented an increased risk for cervical intraepithelial neoplasm (CIN), the precursor lesion of ICC, among HIV-infected women, but the role of HIV in ICC development is still discussed (International Agency for Research on Cancer, 1996). A lack of clear impact of the spread of HIV infection on cervical cancer incidence trends and/or increased cervical cancer risk in women with HIV/AIDS has been reported in the United States (Rabkin et al., 1993; Goedert et al., 1998) and Africa (Bassett et al., 1995). However, women with, or at risk for, HIV infection may die before CIN progresses to ICC, or they may be regularly screened and treated for cervical dysplasia, thus preventing progression to ICC. Among women with AIDS reported to the Italian AIDS Registry between 1993 and 1995, the frequency of ICC as AIDS-defining disease was nearly 3 times higher among intravenous drug users (IDU) than among those infected through heterosexual contacts (Serraino et al., 1996), suggesting that the practice of at-risk sexual behavior (e.g., prostitution) and/or the lack of appropriate screen- ing may favor the occurrence of ICC among HIV-infected IDU women. We have conducted the present study to assess ICC risk among HIV-positive IDU and heterosexual women, and among HIV-negative IDU women. MATERIAL AND METHODS In this investigation, longitudinal data from a South-eastern French HIV clinical database (the DMI-2 study), from the Italian HIV Seroconverter Study (ISS) and from the clinical database of former IDUs admitted to the San Patrignano Community, Northern Italy, were combined in order to assess ICC (International Classifi- cation of Disease–9th Revision, code 180) risk among women with, or at risk for, HIV infection. The analysis was restricted to women aged between 15 and 49 years who were IDU or who acquired HIV infection through heterosexual intercourse. DMI-2 HIV clinical database Included in this study were 1,218 women followed between 1 January 1988 and 31 January 1998 at the Nice University Hospital. Details on the DMI-2 HIV clinical database have been published (Pradier et al., 1998). At baseline, information was collected on sociodemographic characteristics, HIV exposure category, date of first HIV-positive test, biological markers (e.g., the CD4 + cell count and plasma viral load) and clinical conditions. Follow-up visits were scheduled at least every 6 months, although the timing could vary according to the patient’s immunological status. Person- years at risk were computed from the first visit up to the date of death, or of ICC diagnosis or of last follow-up. All ICC diagnoses were histologically confirmed by the Pathology Department of Nice University Hospital. For patients who missed the follow-up visits for more than 1 year, information on AIDS and on vital status was actively elicited from either the French National AIDS Registry, clinical records or the Census Bureau of the town of residence. ISS cohort The ISS is an ongoing longitudinal investigation conducted by 16 clinical centers (for details of the overall study design, see Rezza et al., 1989; and Serraino et al., 1997). Included in this study were 484 women (272 IDUs and 212 heterosexuals) who had had a documented HIV-seronegative test followed by a positive con- firmed one. The maximum accepted lag between the 2 HIV tests was 2 years, and the midpoint between the 2 dates was used to estimate the seroconversion period. Person-years at risk for ICC were computed from the estimated HIV seroconversion period to death, ICC diagnosis, or to a cutoff date (i.e., 30 June 1997). ICC diagnoses were histologically confirmed by the collaborating pathologists. To reduce follow-up losses, a linkage with the Italian National AIDS Registry was carried on for AIDS-free individuals at the visit that preceded the cutoff date. Further information on Grant sponsor: Italian Ministry of Health, Istituto Superiore di Sanita `, Progetto AIDS 1998; Grant number: 20A.0.19. *Correspondence to: Epidemiology Unit, IRCCS, L. Spallanzani Via Portu- ense 292, 00149 Roma, Italy. Fax: +39/06/5594224. E-mail: serrainod@ets.it Received 25 November 1998; Revised 8 March 1999 Int. J. Cancer: 82, 334–337 (1999)  1999 Wiley-Liss, Inc. Publication of the International Union Against Cancer Publication de l’Union Internationale Contre le Cancer