Objective: To evaluate prospectively the safety of the infrared coagulator (IRC) as a treatment for anal high-grade squamous intraepithelial lesions (HSILs) in HIV-infected individuals and to seek preliminary evidence for efficacy.
Methods: HIV-infected patients with =3 biopsy-proven internal anal HSILs received office-based treatment with the IRC at participating AIDS Malignancy Consortium sites. Treatments were performed during high-resolution anoscopy (HRA) under local anesthesia.
We previously reported that BMRF-2, an Epstein-Barr virus (EBV) glycoprotein, binds to beta1 family integrins and is important for EBV infection of polarized oral epithelial cells. To further study the functions of BMRF-2, we constructed a recombinant EBV that lacks BMRF-2 expression by homologous recombination in B95-8 cells. We found that lack of BMRF-2 resulted in about 50% reduction of EBV attachment to oral epithelial cells, but not to B lymphocytes, suggesting that BMRF-2 is critical for EBV infection in oral epithelial cells, but not in B lymphocytes.
View Article and Find Full Text PDFMulticellular tumor spheroids (MCTS) are three dimensional cell culture systems induced by suspension culture. MCTS are widely used in cancer research because of their similarity to solid tumors. CaSki cells are derived from a metastatic cervical cancer containing human papillomavirus 16 (HPV16).
View Article and Find Full Text PDFObjective: Cutaneous anergy testing evaluates delayed type hypersensitivity responses and is, in essence, an in-vivo measure of cell-mediated immune function at an epithelial surface. This study assessed the relationship of anergy test results with cervical infection by human papillomavirus (HPV) and cervical neoplasia in HIV-seropositive and seronegative women.
Methods: HIV-seropositive (n = 1029) and HIV-seronegative (n = 272) women enrolled in a long-term cohort study were followed semi-annually with HPV-DNA testing and cytology.
Rates of cervical and anal human papillomavirus (HPV) infection and abnormal cytology are high in HIV-infected women, as are rates of anal HPV infection and abnormal cytology in HIV-infected men who have sex with men (MSM). Available evidence indicates that the incidence of anal cancer in HIV-infected MSM has increased in association with prolonged life expectancy achieved with antiretroviral therapy. Routine screening for cervical neoplasia is recommended for HIV-infected women.
View Article and Find Full Text PDFAnal dysplasia (low-grade squamous intraepithelial lesions, LSIL; high-grade squamous intraepithelial lesions, HSIL) is a challenging disease for the surgeon. We reviewed 42 patients that underwent high-resolution anoscopy (HRA)-targeted surgical therapy of anal dysplasia in the past 10 years. Patients were followed up in the Anal Neoplasia Clinic with physical examination, cytology, HRA, and biopsy if indicated.
View Article and Find Full Text PDFWhile much is known about the natural history of cervical human papillomavirus (HPV) infection and its consequences, including cervical intraepithelial neoplasia and cervical cancer, relatively little is known about the natural history of anogenital HPV infection and diseases in men. In part this reflects difficulties in penile sampling and visual assessment of penile lesions. Anal HPV infection and disease also remain poorly understood.
View Article and Find Full Text PDFEpstein-Barr virus (EBV) causes hairy leukoplakia (HL), a benign lesion of oral epithelium that occurs primarily in the setting of human immunodeficiency virus (HIV)-associated immunodeficiency. However, the mechanisms of EBV infection of oral epithelium are poorly understood. Analysis of HL tissues shows a small number of EBV-positive intraepithelial macrophages and dendritic/Langerhans cells.
View Article and Find Full Text PDFHuman papillomavirus (HPV) infection is etiologically associated with a subset of oral cancers, and yet, the natural history of oral HPV infection remains unexplored. The feasibility of studying oral HPV natural history was evaluated by collecting oral rinse samples on 2 occasions at a 6-month interval from 136 HIV-positive and 63 HIV-negative participants. Cervical vaginal lavage samples were concurrently collected for comparison.
View Article and Find Full Text PDFThe calcium-binding proteins S100A8 and S100A9 and their heterocomplex calprotectin are abundant cytosolic constituents in human neutrophils, constitutively expressed by mucosal epithelium and in association with inflammation by epidermal keratinocytes. S100A8 and S100A9 are pleiotropic proteins, which partake in the regulation of leukocyte migration. This study was designed to investigate the effect of S100A9 on neutrophil migration and to explore the mechanisms that regulate this effect.
View Article and Find Full Text PDFEpstein-Barr virus (EBV) BMRF-2 protein interaction with the beta1 family of integrins plays an important role in EBV infection of polarized oral epithelial cells. In this work, we characterized BMRF-2 protein expression in EBV-infected B lymphoblastoid and polarized oral epithelial cells, and in hairy leukoplakia (HL) epithelium. BMRF-2 expression in B cells and polarized oral epithelial cells was associated with the EBV lytic infection.
View Article and Find Full Text PDFInt J Gynaecol Obstet
November 2006
Human immunodeficiency virus (HIV)-positive women and women with transplant-associated immunocompromise are at increased risk for cervical intraepithelial neoplasia (CIN) and cervical cancer compared with healthy, immunocompetent women. HPV often manifests as a "field" effect in immunocompromised women who are also at increased risk for vaginal, vulval, and anal intraepithelial neoplasia. Immunocompromised women require careful follow-up with regular cy-tologic screening, and there should be a low threshold for performing colposcopic evaluation in these women.
View Article and Find Full Text PDFObjective: Little is known about effects of vaginal lubricants with barrier contraceptives on detection of sexually transmissible infections. We hypothesized that Replens gel used with a diaphragm would neither inhibit human papillomavirus (HPV) detection in cervical samples and chlamydia (CT) and gonorrhea (GC) detection in urine samples, nor affect cervical cytology quality.
Materials And Methods: After a clinician-collected cervical sample and a self-collected vaginal sample for HPV detection ("pregel" specimens), women placed a diaphragm containing Replens gel into the vagina.
Objective: Because parity is a reported risk factor for cervical cancer, we sought to estimate the effects of pregnancy on the prevalence, incident detection, and copy number of human papillomavirus (HPV) among human immunodeficiency virus (HIV)-infected women, patients at high risk for cervical cancer.
Methods: Human immunodeficiency virus-infected women who had a pregnancy in the Women's Interagency HIV Study (n = 178) and the Women and Infants Transmission Study (n = 450) underwent serial type-specific HPV DNA testing using MY09/MY11 polymerase chain reaction. During pregnancy and during the prepregnancy and postpregnancy periods, we assessed HPV prevalence, incident detection, and HPV copy number (estimated using hybridization signal strength) of both oncogenic and nononcogenic HPV.
HIV-positive as well as other immunocompromised women and men have increased risk of human papillomavirus (HPV)-associated anogenital and oral cancers. The effectiveness of a HPV vaccine to reduce the incidence of these tumors in immunocompromised individuals may depend on several factors, including the effects of immunocompromise on the response to vaccination, the extent of prior infection with the HPV types included in the vaccine, whether immunocompromised women and men have tumors that contain types of HPV not in the vaccines more often than the general population, and whether or not immunization occurs before immunocompromise is severe. Clinical studies are needed to determine HPV vaccine safety and effectiveness in different populations of immunocompromised women and men.
View Article and Find Full Text PDFThe inflammatory response to tissue injury is a multi-faceted process. During this process, neutrophils migrate in the extravascular spaces, directed to the site of injury by chemical gradients generated by chemotactic molecules. S100A8, a protein associated with a wide variety of inflammatory conditions, is heavily over-expressed in association with inflammation.
View Article and Find Full Text PDFPurpose Of Review: Human papillomavirus-related anogenital cancers are theoretically preventable. Many HIV-infected women do not undergo routine cervical cytology screening, however, and there are currently no routine anal cytology screening programs. This review focuses on recent developments that may impact on the future incidence of these cancers: the effect of highly active antiretroviral therapy and the imminent approval of vaccines to prevent initial human papillomavirus infection.
View Article and Find Full Text PDFIndividuals with human immunodeficiency virus (HIV) infection are at increased risk for human papillomavirus-related squamous cell cancer of the anus. Screening HIV-infected patients for squamous cell cancer of the anus and human papillomavirus-related anal dysplasia may prevent excess morbidity and mortality. We have conducted a systematic review of the indirect evidence in the literature regarding the utility of anal Papanicolau (Pap) smear screening of HIV-infected individuals in the highly active antiretroviral therapy era.
View Article and Find Full Text PDFAnogenital cancers are closely associated with human papillomavirus (HPV), and HPV-infected individuals, particularly those with high-grade dysplasias, are at increased risk for cervical and anal cancers. Although genomic instability has been documented in HPV-infected keratinocytes, the full spectrum of genetic changes in HPV-associated lesions has not been fully defined. To address this, we examined an HPV16-transformed foreskin keratinocyte cell line, 16-MT, by GTG-banding, spectral karyotyping (SKY), and array comparative genomic hybridization (array CGH); these analyses revealed multiple numerical, complex, and cryptic chromosome rearrangements.
View Article and Find Full Text PDFObjectives: To test a therapeutic vaccine consisting of a fusion of the human papillomavirus (HPV) 16 E7 protein and the Mycobacterium bovis heat shock protein 65 (SGN-00101) to treat high-grade anal intraepithelial neoplasia (HG-AIN) in HIV-positive individuals.
Design: A phase I/II trial with three cohorts of five participants each, sequentially assigned to receive 100, 500 or 1000 microg SGN-00101, injected three times subcutaneously in alternating thighs at 4-week intervals. Anal disease was assessed at baseline, 8, 12, 24 and 48 weeks and was classified as the more severe of anal cytology and anal biopsy.
HIV-positive men and women are at increased risk of anogenital and oral HPV infection. The risks for HPV-associated high-grade intra-epithelial neoplasia (IN) and cancer are also increased. The prevalence of oral, anal, and cervical HPV infection in HIV-positive individuals compared with HIV-negative individuals increases with progressively lower CD4+ levels, as does incident high-grade IN.
View Article and Find Full Text PDFSerial measurement of antibodies has not been used to provide evidence of active viral replication of human papillomavirus (HPV). Serum specimens from sequential study visits contributed by 642 human immunodeficiency virus (HIV)-positive and 116 HIV-negative participants enrolled in the Women's Interagency HIV Study were used to detect significant rises in HPV type 16 (HPV-16) antibody levels. Factors associated with a significant rise were identified using multivariable logistic regression models with generalized estimating equations.
View Article and Find Full Text PDFAnal intraepithelial neoplasia (AIN) is the likely precursor to anal cancer. AIN is associated with human papillomavirus (HPV) infection, and HPV-associated genomic instability may play an important role in the progression of squamous intraepithelial neoplasia to cancer. Microarray-based comparative genome hybridization (aCGH) was performed on DNA from AIN specimens to determine the host genomic alterations and their correlation with HPV DNA integration or rearrangement.
View Article and Find Full Text PDFHighly oncogenic human papillomavirus (HPV) 16 and 18 variants might be expected to be particularly aggressive in HIV-positive women. The association of HPV16 and 18 variant lineages with race, human immunodeficiency virus (HIV) coinfection, CD4+ T-cell count, HIV-RNA level, time-to-clearance of HPV infection and presence of squamous intraepithelial lesions (SIL) among women in the Women's Interagency HIV Study was studied. Subjects were followed semi-annually with Pap smear and cervicovaginal lavage (CVL).
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