Cervical squamous intraepithelial lesions of low-grade in HIV-infected women: recurrence, persistence, and progression, in treated and untreated women

Department of General and Specialistic Surgical Sciences, Section of Gynaecology and Obstetrics, University of Bari, Piazza Giulio Cesare, 70124 Bari, Italy.
European Journal of Obstetrics & Gynecology and Reproductive Biology (Impact Factor: 1.63). 09/2005; 121(2):226-32. DOI: 10.1016/j.ejogrb.2004.12.003
Source: PubMed

ABSTRACT Human immunodeficiency virus (HIV)-infected patients are more predisposed than HIV-negative women to develop squamous intraepithelial lesions (SIL) of the uterine cervix, and cervical dysplasia may be of higher grade in HIV-positive women than in HIV-negative subjects, with more extensive and multi-centric involvement of the lower genital tract by human papillomavirus (HPV)-associated lesions. Moreover, recurrence and progression rate of cervical intraepithelial neoplasia (CIN) is particularly higher in immunocompromised women.
Retrospective case-control study of HIV-positive women and HIV-negative controls, all affected by low-grade SIL of the uterine cervix, treated by loop excision or followed-up without treatment. Correlation of progression and recurrence of SIL with HIV status and CD4+ count.
From September 1990 to October 1997, 75 HIV-positive low-grade-SIL patients, 47 treated and 28 followed-up without treatment, and 75 HIV-negative low-grade-SIL controls, 45 treated and 30 followed-up.
Among treated patients, 17/47 (36.2%) HIV-positive and 5/45 (11.1%) controls had recurrence (P < 0.0101, O.R. = 4.53, 95% CI = 1.5-13.7), progression of untreated lesion was seen in 15/28 (53.6%) HIV-positive and 7/30 (23%) controls (P < 0.05, O.R. = 3.79, 95% CI = 1.23-11.69). The risk of recurrence or progression of low-grade SIL linked to HIV seropositivity is about 4-5 times higher in comparison with seronegative counterpart, matched for age, risk factors and lesion size. More significantly, considering the cut-off of 200 CD4+/mm(3) in HIV-positive women, 13/17 cases of recurrence (P < 0.05, O.R. = 4.88, 95% CI = 1.28-18.58) and 10/15 cases with progression (P < 0.05, O.R. = 6.67, 95% CI = 1.24-35.73) were immunocompromised (<200 CD4+/mm3), with a significant higher risk of recurrence or progression linked to immunodeficiency status. Considering time of progression or recurrence, during follow-up, Kaplan-Meier curves shows that HIV-positive status and immunodeficiency are correlated with more rapid evolution of cervical dysplasia and HPV-related lesions: comparison of recurrence in treated patients report P < 0.005 and progression in untreated P<0.05 (Mantel-Haenszel log-rank test).
Immunological status seems to be a determinant factor in prognosis of cervical SIL, HIV-positive women affected by this lesion, even if low-grade, need more aggressive management than the immunocompetent counterpart. Strict cytologic and colposcopic screening is recommended and CD4+ count and HPV-DNA testing may be useful risk indicators. Excisional procedures are preferred, while ablative treatments or wait and see policy may expose to some risk this type of population with poor compliance to follow-up.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background. HIV-infected adolescents may be at higher risk for high-grade cervical lesions than HIV-uninfected adolescents. The purpose of this study was to compare the prevalence of high-risk HPV (HR-HPV) infections and Pap smear abnormalities between these two groups. Methods. In this cross-sectional study, we compared the HPV DNA and Pap smear results between 35 HIV-infected and 50 HIV-uninfected adolescents in order to determine the prevalence of HR-HPV genotypes and cervical cytological abnormalities. Comparisons were made using Pearson χ (2) and independent-samples t-tests analyses, and associations between demographic and behavioral characteristics and HPV infections were examined. Results. HIV-infected participants were more likely to be infected with any HPV (88.6% versus 48.0%; P < 0.001) and with at least one HR-HPV (60.0% versus 24.0%; P = 0.001), and to have multiple concurrent HPV infections (68.6% versus 22.0%; P < 0.001). HPV 16 and 18 were relatively underrepresented among HR-HPV infections. Abnormal Pap test results were more common among HIV-infected participants (28.8% versus 12.0%; P = 0.054). A history of smoking was associated with HR-HPV infection. Conclusions. HIV-infected adolescents have an increased risk of infection with HR-HPV and of Pap test abnormalities. The majority of HR-HPV infections among our participants would not be prevented by the currently available vaccinations against HPV.
    Infectious Diseases in Obstetrics and Gynecology 01/2014; 2014:498048. DOI:10.1155/2014/498048
  • [Show abstract] [Hide abstract]
    ABSTRACT: Estimation of the prevalence of high-risk human papillomavirus (HPV) genotypes in female renal transplant recipients is important for formulating strategies for prevention and screening of cervical cancer in the susceptible group. Data from developing countries are very limited. The study was prospective, cross-sectional, and hospital-based. Female renal transplant recipients, who had received the graft at least 6 mo earlier, were enrolled. Women who visited the outpatient unit for varied complaints and who underwent a normal cervical examination were recruited as controls. A pap smear was obtained in all women. HPV genotyping array kit was utilized for identifying 21 HPV genotypes. Forty renal transplant recipient women and 80 controls were enrolled. The median age of cases and controls was 40 yr (range, 24-69 yr) and 38 yr (range, 23-72 yr), respectively. The mean duration since transplant was 53±42.6 mo (range, 6-168 mo). There was no evidence of cervical dysplasia in any pap smear. High-risk HPV was detected in 32.5% (13/40) and 17.5% (14/80) of cases and controls, respectively (P=0.18). Of the 21 genotypes screened, 7 subtypes were detected. HPV 16 and 31 were the most common (5/13; 38.5%) subtypes observed in the cases, followed by HPV 18 (30.7%). HPV 16 was the most common subtype in controls (10/14; 71.4%). Five (38.5%) renal transplant recipients harbored multiple HPV genotypes, as compared with 4 (28.6%) controls (P=1.0). The prevalence of high-risk HPV in female renal transplant recipients was 1.9 times that observed among controls, although there was no evidence of cervical dysplasia.
    International Journal of Gynecological Pathology 07/2014; 33(5). DOI:10.1097/PGP.0b013e3182a54ada · 1.63 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cervical cancer kills more women in low-income nations than any other malignancy. A variety of research and demonstration efforts have proven the efficacy and effectiveness of low-cost cervical cancer prevention methods but none in routine program implementation settings of the developing world, particularly in HIV-infected women. In our public sector cervical cancer prevention program in Zambia, nurses conduct screening using visual inspection with acetic acid aided by digital cervicography. Women with visible lesions are offered same-visit cryotherapy or referred for histologic evaluation and clinical management. We analyzed clinical outcomes and modeled program effectiveness among HIV-infected women by estimating the total number of cervical cancer deaths prevented through screening and treatment. Between 2006 and 2008, 6572 HIV-infected women were screened, 53.6% (3523) had visible lesions, 58.5% (2062) were eligible for cryotherapy and 41.5% (1461) were referred for histologic evaluation. A total of 75% (1095 out of 1462) of patients who were referred for evaluation complied. Pathology results from 65% (715 out of 1095) of women revealed benign abnormalities in 21% (151), cervical intraepithelial neoplasia (CIN) I in 30% (214), CIN 2/3 in 33% (235) and invasive cervical cancer in 16.1% (115, of which 69% were early stage). Using a conditional probability model, we estimated that our program prevented 142 cervical cancer deaths (high/low range: 238-96) among the 6572 HIV-infected women screened, or one cervical cancer death prevented per 46 (corresponding range: 28-68) HIV-infected women screened. Our prevention efforts using setting-appropriate human resources and technology have reduced morbidity and mortality from cervical cancer among HIV-infected women in Zambia. Financial support for implementing cervical cancer prevention programs integrated within HIV/AIDS care programs is warranted. Our prevention model can serve as the implementation platform for future low-cost HPV-based screening methods, and our results may provide the basis for comparison of programmatic effectiveness of future prevention efforts.
    HIV Therapy 11/2010; 4(6):703-722. DOI:10.2217/hiv.10.52