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: 1.7). 09/2005; 121(2):226-32. DOI: 10.1016/j.ejogrb.2004.12.003
Source: PubMed


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.

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    • "One of the most studied types of immunosuppression is that due to human immunodeficiency virus (HIV) infection [6]. Such infection leads to alterations in cell-mediated immunity, thereby facilitating the acquisition of opportunistic infections and limiting an organism’s ability to produce an efficient immune response [7]. "
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    ABSTRACT: Background HIV infection leads to a decreasing immune response, thereby facilitating the appearance of other infections, one of the most important ones being HPV. However, studies are needed for determining associations between immunodeficiency caused by HIV and/or the presence of HPV during the course of cervical lesions and their degree of malignancy. This study describes the cytological findings revealed by the Papanicolaou test, laboratory characteristics and HPV molecular profile in women with and without HIV infection. Methods A total of 216 HIV-positive and 1,159 HIV-negative women were invited to participate in the study; PCR was used for the molecular detection of HPV in cervical samples. Statistical analysis (such as percentages, Chi-square test and Fisher’s exact test when applicable) determined human papillomavirus (HPV) infection frequency (single and multiple) and the distribution of six types of high-risk-HPV in women with and without HIV infection. Likewise, a logistic regression model was run to evaluate the relationship between HIV-HPV infection and different risk factors. Results An association was found between the frequency of HPV infection and infection involving 2 or more HPV types (also known as multiple HPV infection) in HIV-positive women (69.0% and 54.2%, respectively); such frequency was greater than that found in HIV-negative women (44.3% and 22.7%, respectively). Statistically significant differences were observed between both groups (p = 0.001) regarding HPV presence (both in infection and multiple HPV infection). HPV-16 was the most prevalent type in the population being studied (p = 0.001); other viral types had variable distribution in both groups (HIV-positive and HIV-negative). HPV detection was associated with <500 cell/mm3 CD4-count (p = 0.004) and higher HIV-viral-load (p = 0.001). HPV-DNA detection, <200 cell/mm3 CD4-count (p = 0.001), and higher HIV-viral-load (p = 0.001) were associated with abnormal cytological findings. Conclusions The HIV-1 positive population in this study had high multiple HPV infection prevalence. The results for this population group also suggested a greater association between HPV-DNA presence and cytological findings. HPV detection, together with low CD4 count, could represent useful tools for identifying HIV-positive women at risk of developing cervical lesions.
    BMC Cancer 06/2014; 14(1):451. DOI:10.1186/1471-2407-14-451 · 3.36 Impact Factor
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    • "High HIV viral loads and low CD4 counts are associated with a higher risk of HR-HPV infection and cervical abnormalities [7]. The risk of recurrence or progression of cervical lesions is 4–5 times higher in women living with HIV [8]. Infection with one of the 15 HR-HPV genotypes is significantly more common in HIV-infected women [9], while the distribution of low-risk oncogenic HPV is not affected by HIV status [10]. "
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    ABSTRACT: Cervical cancer is the first female cancer in Lao PDR, a low-income country with no national screening and prevention programs for this human papillomavirus (HPV) associated pathology. HIV-infected women have a higher risk of persistent oncogenic HPV infection.The purpose of this study was to determine the knowledge, awareness and attitudes about cervical cancer among Lao women attending or not an HIV treatment center, in order to understand if this attendance had offered an opportunity for information and prevention. A cross-sectional case-control survey was conducted in three provinces of Lao PDR, Vientiane, Luang Prabang and Savannakhet. Cases were 320 women aged 25 to 65, living with HIV and followed in an HIV treatment center. Controls were 320 women matched for age and place of residence, not attending an HIV treatment center. Cases had a greater number of sexual partners and used condoms more often than controls. Only 36.6% of women had consulted a gynecologist (47.5% among cases and 25.6% among controls, p < 0.001) and 3.9% had benefited from at least one Pap smear screening (5.6% cases and 2.2% controls, p = 0.02). The average knowledge score was 3.5 on a 0 to 13 scale, significantly higher in cases than in controls (p < 0.0001). Despite having a lower education level and economic status, the women living with HIV had a better knowledge about cervical cancer and were more aware than the controls of the risk of developing such a cancer (35.9% vs. 8.4%, p = 0.0001). The main source of information was healthcare professionals. The main reasons for not undergoing Pap smear were the absence of symptoms and the default of medical injunction for cases, the lack of information and ignorance of screening usefulness for controls. In Lao PDR, routine consultation in HIV treatment centers is not enough harnessed to inform women of their high risk of developing cervical cancer, and to perform screening testing and treatment of precancerous lesions. Implementing this cost-effective strategy could be the first step toward a national prevention program for cervical cancer.
    BMC Cancer 03/2014; 14(1):161. DOI:10.1186/1471-2407-14-161 · 3.36 Impact Factor
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    • "Furthermore , compared to their non-infected counterparts, women infected with HIV and who develop cervical cancer are more likely to present with advanced clinical disease [Maiman et al., 1997]. The high prevalence of HPV among women who are HIVpositive can be explained by the tendency for HPV to persist, thus differing from what occurs among immunocompetent individuals [Nappi et al., 2005; Hawes et al., 2006; Palefsky, 2006b; Berrebi et al., 2008; Denny et al., 2008]. "
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    ABSTRACT: The aim of this study was to investigate an association between certain human papillomavirus (HPV) types and human immunodeficiency virus (HIV) infections. Sexually active females (n = 487; 19-61 years old) were enrolled in the study. Subjects underwent Pap testing and evaluations of HIV and HPV infection status on uterine cervical cell samples. HPV genotyping was performed using a Kurabo GeneSQUARE DNA microarray test. Overall, 23 HPV genotypes were detected, and the most prevalent HPV genotype was HPV-52, followed by HPV-39, -54, -45, -56, -53, -31, -42, -16, -68, and -51. HPV-30, -53, -54, -61, and -66, which are associated with abnormal cytology, are categorized as intermediate-risk in this study. Detection of both high- and intermediate-risk HPV types was significantly associated with cervical abnormality and HIV infection. Multivariate analysis revealed that some high-risk HPV types (HPV-31, -45, -51, -56, and -59) and most intermediate-risk HPV types were associated with HIV infection, while the high-risk types (HPV-16, -18, -33, -35, -39, -52, -58, and -68) were not. The oncogenic effect of the most malignant HPV types (e.g., HPV-16 and -18) appear to be lower, while that of intermediate-risk types are greater, in areas with a high prevalence of HIV infection.
    Journal of Medical Virology 11/2011; 83(11):1988-96. DOI:10.1002/jmv.22203 · 2.35 Impact Factor
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