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      Cervical cytological changes in HIV-infected patients attending care and treatment clinic at Muhimbili National Hospital, Dar es Salaam, Tanzania

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          Abstract

          Background

          Tanzania is among Sub-Saharan countries mostly affected by the HIV and AIDS pandemic, females being more vulnerable than males. HIV infected women appear to have a higher rate of persistent infection by high risk types of human papillomavirus (HPV) strongly associated with high-grade squamous intraepithelial lesions (HSIL) and invasive cervical carcinoma. Furthermore, although HIV infection and cervical cancer are major public health problems, the frequency and HIV/HPV association of cervical cancer and HSIL is not well documented in Tanzania, thus limiting the development of preventive and therapeutic strategies.

          Methods

          A prospective unmatched, case-control study of HIV-seropositive, ≥ 18 years of age and consenting non-pregnant patients attending the care and treatment center (CTC) at Muhimbili National Hoospital (MNH) as cases was done between 2005 and 2006. HIV seronegative, non-pregnant and consenting women recruited from the Cervical Cancer Screening unit (CCSU) at ORCI were used as controls while those who did not consent to study participation and/or individuals under < 18 years were excluded. Pap smears were collected for routine cytodiagnosis and P53 immunohistochemistry (IHC). Cervical lesions were classified according to the Modified Bethesda System.

          Results

          A total of 170 participants from the two centers were recruited including 50 HIV-seronegative controls were from the CCSU. Ages ranged from 20-66 years (mean 40.5 years) for cases and 20-69 years (mean 41.6 years) for controls. The age group 36-45 years was the most affected by HIV (39.2%, n = 47). Cervicitis, squamous intraepithelial lesions (SIL) and carcinoma constituted 28.3% (n = 34), 38.3% (n = 46) and 5.8% (n = 7) respectively among cases, and 28% (n = 14), 34% (n = 17) and 2% (n = 1) for controls, although this was not statistically significant (P-value = 0.61). IHC showed that p53 was not detectable in HPV + Pap smears and cell blocks indicating possible degradation.

          Conclusions

          The frequency of SIL and carcinoma appeared to be higher among HIV-infected women on HAART compared to seronegative controls and as expected increased with age. HIV seropositive patients appeared to present earlier with SIL compared to those HIV seronegative suggesting a role of HIV in altering the natural history of HPV infection and cervical lesions. The absence of p53 immunoreactivity in HPV + lesions is indicative of the ability of HPV E6 proteins to interact with the tumor suppressor gene and pave way for viral-induced oncogenesis in the studied Tanzanian women.

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          Most cited references32

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          Human papillomavirus infection in women infected with the human immunodeficiency virus.

          Among women infected with the human immunodeficiency virus (HIV), there is a high prevalence of human papillomavirus (HPV) infections. However, little is known about the natural history of HPV infections in HIV-seropositive women, and persistent HPV infections may explain the increased risk of cervical squamous intraepithelial lesions and invasive cervical cancer in HIV-seropositive women. A total of 220 HIV-seropositive and 231 HIV-seronegative women in the New York City area were evaluated at two or more semiannual gynecologic examinations that included a Pap test, a test for HPV DNA, and colposcopy. HPV DNA was detected at the initial examination in 56 percent of the HIV-seropositive and 31 percent of the HIV-seronegative women. After four examinations, the cumulative prevalence of HPV infection was 83 percent in the seropositive women and 62 percent in the seronegative women (P<0.001). Persistent HPV infections were found in 24 percent of the seropositive women but in only 4 percent of the seronegative women (P<0.001). Twenty percent of the seropositive women and 3 percent of the seronegative women had persistent infections with HPV-16-associated viral types (16, 31, 33, 35, or 58) or HPV-18-associated types (18 or 45) (P<0.001), which are most strongly associated with cervical cancer. The detection of HPV DNA in women with previously negative tests was not associated with sexual activity during the interval since the preceding examination. HIV-seropositive women have a high rate of persistent HPV infections with the types of HPV that are strongly associated with the development of high-grade squamous intraepithelial lesions and invasive cervical cancer. These persistent infections may explain the increased incidence of squamous intraepithelial lesions in HIV-seropositive women.
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            Incidence of cervical squamous intraepithelial lesions in HIV-infected women.

            Women infected with human immunodeficiency virus (HIV) are at increased risk for cervical squamous intraepithelial lesions (SILs), the precursors to invasive cervical cancer. However, little is known about the causes of this association. To compare the incidence of SILs in HIV-infected vs uninfected women and to determine the role of risk factors in the pathogenesis of such lesions. Prospective cohort study conducted from October 1,1991, to June 30, 1996. Urban clinics for sexually transmitted diseases, HIV infection, and methadone maintenance. A total of 328 HIV-infected and 325 uninfected women with no evidence of SILs by Papanicolaou test or colposcopy at study entry. Incident SILs confirmed by biopsy, compared by HIV status and risk factors. During about 30 months of follow-up, 67 (20%) HIV-infected and 16 (5%) uninfected women developed a SIL (incidence of 8.3 and 1.8 cases per 100 person-years in sociodemographically similar infected and uninfected women, respectively [P<.001]). Of incident SILs, 91% were low grade in HIV-infected women vs 75% in uninfected women. No invasive cervical cancers were identified. By multivariate analysis, significant risk factors for incident SILs were HIV infection (relative risk [RR], 3.2; 95% confidence interval [CI], 1.7-6.1), transient human papillomavirus (HPV) DNA detection (RR, 5.5; 95% CI, 1.4-21.9), persistent HPV DNA types other than 16 or 18 (RR, 7.6; 95% CI, 1.9-30.3), persistent HPV DNA types 16 and 18 (RR, 11.6; 95% CI, 2.7-50.7), and younger age (<37.5 years; RR, 2.1; 95% CI, 1.3-3.4). In our study, 1 in 5 HIV-infected women with no evidence of cervical disease developed biopsy-confirmed SILs within 3 years, highlighting the importance of cervical cancer screening programs in this population.
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              • Record: found
              • Abstract: not found
              • Article: not found

              A follow-up study of patients with cervical dysplasia.

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                Author and article information

                Journal
                Infect Agent Cancer
                Infectious Agents and Cancer
                BioMed Central
                1750-9378
                2012
                15 February 2012
                : 7
                : 3
                Affiliations
                [1 ]Department of Pathology, Muhimbili University of Health and Allied Sciences (MUHAS), P.O. Box 65001, Dar es Salaam, Tanzania
                Article
                1750-9378-7-3
                10.1186/1750-9378-7-3
                3298791
                22335893
                daed63fe-15fc-4aa9-87c9-9e55d9821f41
                Copyright ©2012 Mwakigonja et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 October 2011
                : 15 February 2012
                Categories
                Research Article

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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