The influence of human papillomavirus type and HIV status on the lymphomononuclear cell profile in patients with cervical intraepithelial lesions of different severity.

BACKGROUND: Immunological alterations are implicated in the increased prevalence of high-grade squamous intraepithelial lesions (HG-SIL) and persistent human papillomavirus (HPV) infection. This study evaluated the expression of CD4, CD8, CD25 (IL-2Ralpha) and CD28 antigens from SIL biopsies, stratified by HIV status and HPV-type. Biopsies specimens from 82 (35 HIV+) women with a normal cervix, low-grade (LG-SIL) or high-grade lesions (HG-SIL) were studied. CD molecule expression was evaluated by immunohistochemistry and HPV detection/typing performed using PCR techniques. RESULTS: CD4 stromal staining was increased in patients with HPV18. Women with HPV16 infection showed decreased: a) CD8 and CD25 stromal staining, b) CD25 staining in LG-SIL epithelium and in HG-SIL stroma. In HIV- women samples, CD28 epithelial staining and CD8 stromal staining surrounding metaplastic epithelium were less intense and even absent, as compared to HIV+ women. Both epithelial and stromal CD8 staining was more intense in the HG-SIL/HIV+ group than in the HG-SIL/HIV- group. Positive correlations were observed between CD4/CD25, CD4/CD28 and CD25/CD28 in the stroma and CD25/CD28 in the epithelium. CONCLUSION: HIV status and HPV-type may influence the lymphomononuclear cell profile present in the spectrum of cervical lesions. The knowledge of the infiltrating cell profile in cervical tumours may help the development of specific anti-tumoural strategies.

HLA-G polymorphisms in women with squamous intraepithelial lesions harboring human papillomavirus.

Human papillomavirus (HPV) infection is etiologically associated with low- (LSIL) and high-grade squamous intraepithelial lesions (HSIL) and with cervical cancer. The progression or regression of the lesions may depend, among other factors, on the host heritable immune response. Because human leukocyte antigen (HLA)-G molecules are involved in the modulation of innate and adaptive immune responses, and because no previous studies have evaluated HLA-G polymorphism in patients with SIL, we conducted a study to assess the association between HLA-G polymorphisms and cervical lesions harboring HPV infection. Cervico-vaginal scrapings and blood samples were collected from 125 women with SIL (68 LSIL and 57 HSIL) and from 94 healthy women without HPV infection and cytological abnormalities. HPV type and HLA-G polymorphisms in exons 2, 3 and 8 (14 bp insertion/deletion) were evaluated by PCR methodology, and digested with restriction endonucleases. The Genepop software and the EM and PHASE algorithms were used for statistical analysis. A significant protective association was observed between the presence of the G(*)0103 allele and SIL and between the G0101/G0104 genotype and HSIL in the group of patients compared to control. The presence of the G0104/+14 bp and G0104/-14 bp haplotypes conferred susceptibility to SIL compared to control. In addition, patients possessing the G0104/+14 bp haplotype and harboring HPV-16 and -18 co-infections were particularly associated with HSIL. These findings suggest that HLA-G polymorphisms may be associated with HPV infection and SIL, consequently representing a profile of predisposition to cervical cancer.

Classical and non-classical HLA molecules and p16(INK4a) expression in precursors lesions and invasive cervical cancer.

OBJECTIVES: Viruses and tumour cells may regulate the expression of HLA molecules on the cell surface to escape immune system surveillance. Absence of classical HLA class I molecules may impair the action of specific cytotoxic cells, whereas non-classical HLA class I molecules may regulate innate and adaptive immune cells. We assess here the possible associations between classical/non-classical class I HLA and p16(INK4a) molecule expression in cervical biopsies of women infected with HPV, stratified according to grade of the lesion and HPV type. STUDY DESIGN: Cervical biopsies (N=74) presenting cervical intraepithelial neoplasia grade 1 (CIN1) (n=31), CIN2-3 (n=19), and invasive cancer (n=14) were evaluated alongside 10 normal cervical specimens. RESULTS: HLA-A/B/C/G staining was observed in the early stages of HPV infection. A significant association was detected between HLA-A/B/C staining and HPV16/18 infection (OR=0.12, 95%CI: 0.0163-0.7899; p=0.04). HLA-E expression increased with the progression of the lesion (chi(2)-test for trend=4.01; p=0.05), and a significant association was found between HLA-E staining and HPV16/18 infection (OR=11.25, 95%CI: 2.324-54.465; p=0.003). Irrespective of the grade of the lesion, HLA-A/B/C staining and p16(INK4a) presented a good concordance (Kappa: 0.67). CONCLUSIONS: HLA-E overexpression seemed to be associated with invasive cancer and HPV16/18 infection.

A pilot case-control association study of cytokine polymorphisms in Brazilian women presenting with HPV-related cervical lesions.

OBJECTIVE AND STUDY DESIGN: A case-control study was conducted on 42 Brazilian women presenting with human papilloma virus (HPV) infection and cervical lesion and 87 HPV-negative women to evaluate single nucleotide polymorphisms observed in TNF-alpha, TGF-beta, IL-10, IL-6, and IFN-gamma genes. RESULTS AND CONCLUSION: No significant association was observed on the cytokine polymorphisms analyzed in this series. Larger studies using cytokine polymorphisms may be useful for providing further information regarding their influence or not in HPV-related cervical lesions.

HPV type infection in different anogenital sites among HIV-positive Brazilian women.

OBJECTIVES: To evaluate the prevalence of human papillomavirus (HPV) types, and risk factors for HPV positivity across cervix, vagina and anus, we conducted a study among 138 women with human immunodeficiency virus (HIV). GOAL: Compare the prevalence of different HPV types and the risk factors for HPV positivity in three sites. RESULTS: The most frequently detected HPV types in all sites were, in decreasing order, HPV16, 53, 18, 61 and 81. Agreement between the cervix and vagina was good (kappa 0.60 - 0.80) for HPV16 and 53 and excellent (Kappa > 0.80) for HPV18 and 61. HPV positivity was inversely associated with age for all combinations including the anal site. CONCLUSION: In HIV positive women, HPV18 is the most spread HPV type found in combinations of anal and genital sites. The relationship of anal to genital infection has implications for the development of anal malignancies. Thus, the efficacy of the current HPV vaccine may be considered not only for the cervix, but also for prevention of HPV18 anal infection among immunossuppressed individuals.

Human papillomavirus types among women infected with HIV: a meta-analysis.

BACKGROUND: HIV-positive women have a high prevalence of human papillomavirus (HPV) infection and are infected with a broader range of HPV types than HIV-negative women. It is not known to what extent these different types are associated with high-grade squamous intraepithelial lesions (HSIL) and cancer. METHODS: Meta-analysis of HPV type-specific prevalence among HIV-positive women, stratified by geographical region and by cervical cytology: normal, atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesions (ASCUS/LSIL) or HSIL. RESULTS: In 20 studies, 5578 HIV-positive women were identified, largely from North America but also Africa, Asia, Europe and South/Central America. For 3230 with no cytological abnormalities, prevalence was 36.3% for any HPV and 11.9% for multiple HPV types. The six most common high-risk HPV types were 16 (4.5%), 58 (3.6%), 18 (3.1%), 52 (2.8%), 31 (2.0%) and 33 (2.0%). HPV16 was also the most common type in 2053 HIV-positive women with ASCUS/LSIL and 295 with HSIL. Those with HSIL were significantly less likely to be infected with HPV16 (odds ratio, 0.6; 95% confidence interval, 0.4-0.7) than the general female population with HSIL. In contrast, HIV-positive women with HSIL were significantly more likely to be infected with HPV types 11, 18, 33, 51, 52, 53, 58 and 61, and with multiple HPV types. CONCLUSIONS: The proportion of HIV-positive women with HPV16 rose with increasing severity of cervical lesions. Nevertheless, HPV16 remained underrepresented in HIV-positive women with HSIL, who showed a higher proportion of other HPV types and multiple types compared with the general female population with HSIL.

[Greater survival among patients with immunogenetic markers of rapid progression to AIDS: subsidies for nursing care]. / Maior sobrevida em pacientes com marcadores imunogenéticos de rápida progressão para a AIDS: subsídios para a assistência de enfermagem.

This study sought subsidies for improving nursing care programs for AIDS patients and aimed to verify the influence of changes in sexual behavior, including the adoption of safe sex practices, associated with the survival of AIDS patients with immunogenetic markers of rapid disease progression. 27 AIDS patients were interviewed, with genetic predisposition to rapid progression to AIDS. Genes were typified through the polymerase chain reaction. In spite of the presence of immunogenetic factors, associated with individual predisposition to a rapid evolution of the disease, changes in sexual behavior, including safe sex practices and antiretroviral therapy, may be related to greater survival. This suggests that counseling, detection of risk attitudes and health education, focusing on positive health behavior, are tools nursing must use with HIV-positive patients, with a view to better quality of life and greater survival among these individuals, even among those with genetic predisposition to rapid disease progression.

Immunohistochemical expression of p16INK4a and bcl-2 according to HPV type and to the progression of cervical squamous intraepithelial lesions.

Inactivation of the cell cycle inhibitor gene p16MTS1 seems to be involved in human papillomavirus (HPV)-related carcinogenesis because E6 and E7 oncoproteins may impair p16INK4a and, indirectly, bcl-2 functions. In this study, we analyzed the role of immunohistochemical expression of p16INK4a and bcl-2 in HPV-infected cervical biopsies as prognostic markers of the progression of squamous intraepithelial lesion (SIL). Sixty-five cervical biopsies were stratified into two subgroups according to the second biopsy: 27 of them maintained a low-grade (LG)-SIL diagnosis, and 38 progressed from LG-SIL to high-grade (HG)-SIL. p16INK4a and bcl-2 quantitative expression levels were measured by the immunoperoxidase method. PCR-DNA techniques were used to detect and type HPV. The Wilcoxon and Fisher exact tests were employed for the statistical analysis. In the group with an LG-SIL diagnosis at the second biopsy, no significant associations were found between p16INK4a and bcl-2 expression and presence of HPV16/18. In the group that progressed to HG-SIL, a significant association was observed between p16INK4a overexpression and HPV16/18 presence (p=0.021), but none with bcl-2 levels. It is concluded that immunohistochemical bcl-2 expression may not be useful for predicting the progression of HPV-related SIL. In contrast, p16INK4a overexpression seemed to be associated with HPV 16 and 18, suggesting that it may be a good marker for predicting SIL progression.

Maior sobrevida em pacientes com marcadores imunogenéticos de rápida progressão para a AIDS: subsídios para a assistência de enfermagem / Greater survival among patients with immunogenetic markers of rapid progression to AIDS: subsidies for nursing care

Com enfoque em subsídios para o aperfeiçoamento de programas de enfermagem, direcionados a pacientes com aids, o presente estudo foi realizado com o objetivo de verificar a influência do comportamento sexual na sobrevida de pacientes com aids, portadores de genes associados à rápida progressão da doença. Foram entrevistados 27 pacientes com aids, geneticamente predispostos à rápida progressão da doença. As tipificações dos genes foram realizadas pela reação em cadeia da polimerase. Os resultados sugerem que, apesar da presença de fatores imunogenéticos, associados à predisposição individual para rápida evolução da doença, as mudanças do comportamento sexual, com adoção de práticas de sexo seguro, junto ao uso da terapia anti-retroviral, podem estar relacionadas com maior sobrevida. O aconselhamento, a detecção de atitudes de risco e a educação para saúde, enfocando o comportamento positivo de saúde, são ferramentas que a enfermagem deve utilizar a portadores do HIV, visando à melhor qualidade de vida e maior sobrevida desses indivíduos, mesmo naqueles geneticamente predispostos à rápida progressão da doença

HPV16, HPV18, and HIV infection may influence cervical cytokine intralesional levels.

Infection with oncogenic human papillomavirus (HPV) is considered to be the major risk to cervical cancer. This study analyzed the influence of HPV infection on cytokine intralesional levels in cervical lesion in the presence or not of HIV infection. Cervical biopsies from 42 women were studied. HPV detection and typing were performed using amplified DNA hybridized with sequence-specific primers, and cytokine intralesional levels were detected using ELISA. HPV16+ biopsies exhibited increased IFN-gamma and IL-10 when compared to HPV16- (P = 0.03 and 0.04, respectively). HPV18+ biopsies exhibited decreased TNF-alpha (P = 0.009) and IFN- gamma (P = 0.01) when compared to HPV18-. In accordance to HIV status, HIV-/HPV16+ patients exhibited increased IFN-gamma when compared to those presenting HIV-/HPV16- (P = 0.007). HIV-/HPV18+ patients presented decreased IFN-gamma when compared to HIV-/HPV18- (P = 0.02). These results suggest that the presence of HPV16 infection may influence cervical lesion installation, and irrespective of HIV status, HPV18 infection may be more aggressive than HPV-16.

Influência da infecção pelo HIV-1 sobre a presença do HPV em lesões do colo uterino / Influence of HIV-1 infection on the presence of HPV in uterine cervix lesions

Analisa a influência da infecção pelo HIV-1 sobre a presença e persistência da infecção pelos HPV16 e HPV18 em mulheres apresentando NIC

Influência do HPV-16 sobre a produção intralesional de IL-10 em mulheres imunogeneticamente responsivas e portadoras do HIV-1 / Influence of the HPV-16 on IL-10 intralesional production in immunogenetically responsive women carrying HIV-1 infection

A infecção pelo papilomavirus humano do tipo 16 - HPV 16, constitui importante fator de risco para o desenvolvimento do câncer cervical. Citocinas são importantes na resposta imune contra infecções virais. Geneticamente determinadas, podem apresentar predomínio para padrão associado com a eliminação do HPV, ou associadas com a persistência da infecção e progressão para lesões cervicais, como a interleucina 10. Além disso, a infecção pelo vírus da imunodeficiência humana do tipo 1, parece ser uma co-morbidade para o desenvolvimento das lesões cervicais

Anogenital warts contributing to the risk of squamous intraepithelial lesions among HIV-positive women of São Paulo, Brazil.

Unsafe sexual practices may expose HIV-positive women to high-grade squamous intraepithelial lesions (SIL) and to infection with oncogenic human papillomavirus (HPV) types. A cross sectional study of 141 HIV-positive women was designed to evaluate risk factors for the development of cervico-vaginal SIL and HPV-DNA detection/typing. Uni- and multivariate forward stepwise analysis was used to determine the relationship between risk variables and HPV infection and between risk behaviour, HPV and HIV infection with development of SIL. Univariate analysis showed that HPV-DNA infection was related to previous and recurrent anogenital warts, male genital warts and cytological alteration. For final multivariate analysis, both HPV type (undetermined- and high-risk, OR=29.3 and 112.0, respectively) were statistically associated (P=0.019) with high-grade cervico-vaginal SIL. The presence of anogenital warts as well as high- and undetermined-risk HPV infection may alert to cyto/histopathological alterations. These results point out the importance of the use of barrier methods and routine early genitoscopy/treatment for HIV-infected partners.

Risk factors associated with genital warts in HIV-positive Brazilian women.

AIMS AND BACKGROUND: In Brazil, the female population has been increasingly infected with human immunodeficiency virus (HIV), and uterine cervix carcinoma now represents the second highest cause of mortality. Although HIV infection among women is associated with an increased prevalence of cervical cancer precursors, the co-infection with human papillomavirus (HPV) is considered to be a necessary but not sufficient factor to induce genital lesions. This study was conducted to identify risk factors associated with the history of genital warts among HIV-positive women. METHODS: A comparative cross-sectional evaluation was applied to 141 HIV-positive women. All patients were submitted to colposcopy, smear cytology, directed biopsy, and HPV-DNA detection. The chi-square, Fisher's exact test, and the odds ratio (OR, 95%; confidence interval, CI) were used to evaluate associations between history of genital warts and risk factors. RESULTS: A history of genital warts presented associations with: a) age at first sexual intercourse < or = 17 years (OR, 0.42; CI, 0.16-1.11); b) history of genital warts in sex partners (OR, 11.39; CI, 4.21-30.76), especially with recurrent episodes (OR, 6.60; CI, 2.69-16.12); c) drug addiction (OR, 2.38; CI, 1.09-5.19), especially in crack users (OR, 5.34; CI, 1.64-17.41); d) cervical HPV infection (OR, 2.75; CI 1.09-6.90); e) cervical infection caused by only one HPV type (OR, 2.77; CI 1.06-7.20); f) perianal HPV infection (OR, 2.30; CI, 0.70-7.56), associated with negative results for undetermined risk HPV (OR, 8.41; P = 0.04); and g) no antiretroviral therapy (OR, 3.41; P = 0.07). CONCLUSIONS: Evaluation of behavioral risk factors associated with a genital wart history is an important tool to prevent and reduce persistent HPV infection, and consequently genital cancer precursors in HIV infected women.

Fatores imunogenéticos envolvidos na progressäo para a AIDS / Immunogenetic factors involved in the progression to AIDS

A síndrome da Imunodeficiência Adquirida - AIDS - é uma doença caracterizada pela progressäo para graves infecçöes oportunistas e neoplasias resultantes da progressiva imunossupressäo adquirida após a infecçäo pelo HIV. A variedade de padröes temporais para iniciaçäo e progressäo para a AIDS leva-nos à hipótese da existência de vários fatores desencadeadores da doença