A Longitudinal Study of Human Papillomavirus DNA Detection in Human Immunodeficiency Virus Type 1-Seropositive and -Seronegative Women

Vernon, Suzanne D.; Reeves, William C.; Clancy, Kelly A.; Laga, Marie; Louis, Michael St.; Gary, Howard E.; Ryder, Robert W.; Manoka, Abib Thiam; Icenogle, Joseph P.

doi:10.1093/infdis/169.5.1108

Cited by 73 publications

(35 citation statements)

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“…(26,32,33) and to augment the relative risk of cervical and anal carcinoma (11,12). However, we and others have pointed out that relatively few squamous invasive cancers develop in tritherapy untreated HIVinfected population despite the high incidence of high-grade CIN (22).…”

Section: Apoptosis and Viruses In Intraepithelial Cervical Lesionsmentioning

confidence: 99%

Increased Apoptosis in Cervical Intraepithelial Neoplasia Associated with HIV Infection: Implication of Oncogenic Human Papillomavirus, Caspases, and Langerhans Cells

Walker

Adle‐Biassette²,

Madelenat

et al. 2005

Clinical Cancer Research

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Purpose: Increasing risk of squamous cervical intraepithelial neoplasia (CIN) exits in HIVinfected women. However, the relatively low incidence of invasive carcinoma in the untreated HIV-infected population suggests an imbalance between cell proliferation and apoptosis. We investigated apoptosis and caspases in cervical samples from this population comparatively to non-HIV-infected and control subjects. Experimental Design: Apoptotic terminal deoxynucleotidyl transferase^mediated dUTP nickend labeling method, immunohistochemistry for caspase-2, caspase-3, caspase-8, caspase-9, and other apoptosis markers were done on 12 normal cervical samples and 103 low-and high-grade cervical lesions, containing human papillomavirus(es) from 35 HIV-negative and 33 HIV-positive women before tritherapy advent. Results: (a) The apoptotic index (AI) in epithelial cells did not vary between normal mucosa and condyloma acuminata infected or not with HIV. (b) AI augmented with the CIN severity in HIV-positive and HIV-negative women. (c) AI dramatically increased in oncogenic human papillomavirus-infected CIN of HIV-positive population compared with the CIN of similar grade in HIV-negative one. This was associated with a greater expression of caspase-8, active caspase-9, and active caspase-3 in those samples. Moreover, densities of Langerhans' cells, involved in apoptotic bodies engulfment, were greatly reduced in CIN of HIV-positive women. In samples, these densities were highly inversely correlated with AI (r = À0.88, P < 0.002).Conclusions: This study provides the first evidence for the strongly enhanced apoptosis levels and caspase expression in CIN of untreated HIV-infected women. We suggest that the reduction in Langerhans'cell number could contribute at least partly to apoptotic cell accumulation.

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Section: Apoptosis and Viruses In Intraepithelial Cervical Lesionsmentioning

confidence: 99%

Increased Apoptosis in Cervical Intraepithelial Neoplasia Associated with HIV Infection: Implication of Oncogenic Human Papillomavirus, Caspases, and Langerhans Cells

Walker

Adle‐Biassette²,

Madelenat

et al. 2005

Clinical Cancer Research

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“…Furthermore, patients infected with human immunodeficiency virus (HIV) have a higher prevalence of HPV infection and malignant anogenital lesions. In HIV-1-positive women, Vernon et al (56) showed that the more immunocompromised is the patient, the more likely she is to carry persistent HPV infections.…”

Section: Immunological Response Against Hpvmentioning

confidence: 99%

Genetic susceptibility to HPV infection and cervical cancer

Maciag¹,

Villa²

1999

Braz J Med Biol Res

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Squamous cell carcinoma of the cervix (SCCC) is one of the leading causes of death in developing countries. Infection with high-risk human papillomavirus (HPV) is the major risk factor to develop malignant lesions in the cervix. Polymorphisms of the MHC and p53 genes seem to influence the outcome of HPV infection and progression to SCCC, although controversial data have been reported. MHC are highly polymorphic genes that encode molecules involved in antigen presentation, playing a key role in immune regulation, while p53 is a tumor suppressor gene that regulates cell proliferation. The HPV E6 protein from high-risk types binds p53 and mediates its degradation by the ubiquitin pathway. The role of these polymorphisms in genetic susceptibility to HPV infection and to SCCC remains under investigation.

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“…HIV-seropositive women who were colposcopically normal had a sevenfold-greater amount of HPV DNA than HIV-seronegative women (18). This conclusion was confirmed by a third group measuring HPV DNA in selfobtained vaginal swabs (11) but was not reached by a fourth group (16). HPV viral load also varied with age (11).…”

mentioning

confidence: 91%

“…The assay we used was demonstrated to be specific for HPV-16 and does not cross-react with other HPV types (6,7,14). Several studies reported a higher quantity of HPV DNA in HIVseropositive than HIV-seronegative women but did not evaluate the impact of HIV-induced immunosuppression on HPV viral load (5,11,12,16,18). One of these studies demonstrated that the amount of HPV DNA increased in HIV-negative and HIV-seropositive women with the presence and grade of cervical lesions (18).…”

mentioning

confidence: 99%

Human Papillomavirus Type 16 Viral Load Is Higher in Human Immunodeficiency Virus-Seropositive Women with High-Grade Squamous Intraepithelial Lesions Than in Those with Normal Cytology Smears

et al. 2004

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Human papillomavirus type 16 (HPV-16) viral load in cervicovaginal lavage samples collected from 66 human immunodeficiency virus-seropositive women was inversely correlated with blood CD4 count (P ‫؍‬ 0.002). HPV-16 viral load was 81-fold higher in women with cervical smears suggestive of high-grade lesions (median, 4,425,883 copies/ g of DNA) than in women with normal smears (median, 54,576), controlling for age (P ‫؍‬ 0.006).Oncogenic human papillomaviruses (HPV) cause squamous intraepithelial lesions (SIL) and cancer of the uterine cervix in human immunodeficiency virus (HIV)-seronegative and -seropositive women (2). HIV-seropositive women are at increased risk compared to HIV-seronegative women for cervical HPV infection and SIL (9). Although HPV infects the genital tract of most HIV-seropositive women, only a minority of HPVinfected women develop persistent HPV infection that may progress into SIL and cancer (2). Biomarkers of HPV infection that could identify HPV-infected women at high risk for persistent infection and SIL would improve screening algorithms for management of HPV-induced cervical lesions.Several studies suggested that an increased HPV DNA viral load could be a candidate marker for the presence of cervical SIL in HIV-seropositive women (12,17,18). Similar studies with HIV-seronegative women on the predictive value of HPV viral load for high-grade-SIL (HSIL) detection yielded conflicting results (4,8,10,13,14,19). Some of the assays used in the latter studies were not HPV type specific or were semiquantitative, while assays using PCR did not take into account the presence of amplification inhibitors or did not estimate the quantity of cellular DNA tested. The latter two factors have been shown to influence HPV viral load determinations (7,14).A recent study validated a real-time PCR assay that measures the quantity of human cells and HPV DNA contained in biological fluids and uses internal controls to screen for the presence of PCR inhibitors (7). That study also reported that samples could selectively inhibit HPV-16 amplification (7). We present here cross-sectional results of cervical HPV-16 viral loads measured in a cohort of Canadian HIV-seropositive women. HPV-16 viral loads measured in cervicovaginal lavage (CVL) samples correlated with blood CD4 ϩ counts and were associated with cervical SIL.Women infected with HPV-16 were selected from participants recruited in The Canadian Women's HIV Study, a crosssectional and cohort study on the relationships between HPV and HIV infection and development of cervical SIL (3). Participants in the study were recruited from 1993 to 2000 across Canada from clinics involved in the care of HIV-infected patients and gave written informed consent (3). Ethics committees of each participating institution approved the study protocol. The demographic characteristics of the HIV-seropositive women have been described elsewhere (3). CVL samples from 732 HIV-seropositive women were screened at inclusion and at 6-month intervals for HPV infection using the MY09-MY1...

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A Longitudinal Study of Human Papillomavirus DNA Detection in Human Immunodeficiency Virus Type 1-Seropositive and -Seronegative Women

Cited by 73 publications

References 0 publications

Increased Apoptosis in Cervical Intraepithelial Neoplasia Associated with HIV Infection: Implication of Oncogenic Human Papillomavirus, Caspases, and Langerhans Cells

Increased Apoptosis in Cervical Intraepithelial Neoplasia Associated with HIV Infection: Implication of Oncogenic Human Papillomavirus, Caspases, and Langerhans Cells

Genetic susceptibility to HPV infection and cervical cancer

Human Papillomavirus Type 16 Viral Load Is Higher in Human Immunodeficiency Virus-Seropositive Women with High-Grade Squamous Intraepithelial Lesions Than in Those with Normal Cytology Smears

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