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1.
J Infect Dis ; 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33220687

RESUMO

OBJECTIVES: Incidence of anal cancer is highest in gay and bisexual men (GBM). A better understanding of the natural history of anal high-risk human papillomavirus (HRHPV) infection is needed for anal cancer prevention. METHODS: The Study of the Prevention of Anal Cancer was a 3-year study of Australian GBM, aged 35 years or older. We examined incidence, clearance and risk factors for 13 HRHPV types tested for at baseline and 3 annual visits. RESULTS: In 525 men with ≥ 2 visits, 348 (66.3%) acquired ≥ 1 incident HRHPV infection. HPV16 incidence rates were similar, but non-16 HRHPV incidence was higher in HIV-positive (51.8/100 person years, PY) than HIV-negative men (36.5/100 PY, p < 0.001). Annual clearance rates of HPV16 (13.21/100 PY, 95% CI 10.53-16.56) were lower than for other HRHPV types. HRHPV clearance rates were not associated with HIV overall but were significantly lower in those with a lower nadir CD4 (<200 cells/µl) for HPV16 (p=0.015) and other HRHPV types (p=0.007). CONCLUSION: The higher incidence of non-16 HRHPV types, coupled with the lower clearance of non-16 HRHPV types in those with past impaired immune function, is consistent with the greater role of non-16 HRHPV in anal cancer in HIV-positive people.

2.
Cancer Epidemiol Biomarkers Prev ; 29(10): 2078-2083, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32732249

RESUMO

BACKGROUND: Anal high-grade squamous intraepithelial lesion (HSIL) can be histomorphologically categorized into anal intraepithelial neoplasia (AIN) grade 2 (AIN2) and grade 3 (AIN3). Different risk factors for these two categories have been described. We investigated whether there were also differences in lesion-specific human papillomavirus (HPV) genotypes. METHODS: The Study of the Prevention of Anal Cancer (SPANC) recruited 617 gay and bisexual men (GBM); 36% of participants were HIV positive. At baseline, 196 men (31.8%) had histologic HSIL lesions. Tissue was available for genotyping in 171, with a total of 239 HSIL lesions (183 AIN3 and 56 AIN2). Using laser capture microdissection, each lesion revealed a maximum of one genotype. RESULTS: High-risk HPV (HR-HPV) genotypes were found in 220 (92.1%) HSIL lesions, with no significant difference between AIN3 (93.4%) and AIN2 (87.5%). AIN3 lesions had significantly more HPV16 (42.1%) than AIN2 lesions (12.5%; P < 0.001) and AIN2 lesions had significantly more non-16 HR-HPV types (75.0%) than AIN3 lesions (51.4%; P = 0.002). These associations were similar for HIV-negative men with HPV16 in 51.1% AIN3 and 18.2% AIN2 (P = 0.001) and non-16 HR-HPV in 40.0% AIN3 and 75.8% AIN2 (P < 0.001). For HIV-positive men, HPV16 remained more frequently detected in AIN3 (33.3% vs. 4.4% for AIN2; P = 0.004), but there was no difference between AIN3 and AIN2 for non-16 HR-HPV (62.4% vs. 73.9%; P = 0.300). CONCLUSIONS: As HPV16 has the strongest link with anal cancer, the subcategorization of HSIL may enable stratification of lesions for anal cancer risk and guide anal HSIL management. IMPACT: Stratification of anal cancer risk by histologic HSIL grade.

3.
Cancer Genomics Proteomics ; 17(5): 615-625, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32859640

RESUMO

BACKGROUND: Few studies have analyzed the association between human telomerase reverse transcriptase (hTERT) protein expression (nuclear and cytoplasmic localization), hTERT methylation status, and human papillomavirus (HPV) genotype infection in cervical cancer. PATIENTS AND METHODS: One hundred seventy-three patients with cervical cancer were analyzed. hTERT protein expression was detected by immunohistochemistry. hTERT DNA methylation analysis was performed using a PCR-RLB-hTERT assay, targeting two regions of the hTERT promoter. Type specific HPV infection was detected by using GP5+/GP6+PCR-RLB. RESULTS: hTERT protein expression was found in both cytoplasm and nucleus (78.0% of the samples showed a cytoplasmic localization and 79.8% had a nuclear localization). A statistically significant association was found between alpha 9 and 7 HPV species with a non-methylation pattern of the hTERT promoter and between these species and high expression of hTERT protein with nuclear localization. CONCLUSION: hTERT protein is found in both the nucleus and cytoplasm of patients with cervical cancer and confirm the relationship between the non-methylated status of hTERT promoter and some HPV species as well as the relationship between these species and hTERT protein expression.

4.
Clin Infect Dis ; 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32342984

RESUMO

BACKGROUND: Gay and bisexual men (GBM) are disproportionately affected by anal cancer. Prevention is hindered by incomplete understanding of the natural history of its precursor, anal high-grade squamous intraepithelial lesions (HSIL). METHODS: The Study of the Prevention of Anal Cancer, conducted between 2010 and 2018, enrolled human immunodeficiency virus (HIV)-positive and HIV-negative GBM aged ≥35 years. Anal cytology and high-resolution anoscopy (HRA) were performed at baseline and 3 annual visits. A composite HSIL diagnosis (cytology ± histology) was used. Cytological high-grade squamous intraepithelial lesions (cHSIL) incidence and clearance rates were calculated with 95% confidence intervals (CIs). Predictors were calculated using Cox regression with hazard ratios (HRs) and 95% CIs. RESULTS: Among 617 men, 220 (35.7%) were HIV-positive, median age 49 years. And 124 incident cHSIL cases occurred over 1097.3 person-years (PY) follow-up (11.3, 95% CI 9.5-13.5 per 100 PY). Significant bivariate predictors of higher incidence included age <45 years (HR 1.64, 95% CI 1.11-2.41), HIV positivity (HR 1.43, 95% CI .99-2.06), prior SIL diagnosis (P-trend < .001) and human papillomavirus (HPV)16 (HR 3.39, 2.38-4.84). Over 695.3 PY follow-up, 153 HSIL cleared (clearance 22.0, 95% CI 18.8-25.8 per 100 PY). Predictors were age < 45 years (HR 1.52, 1.08-2.16), anal intraepithelial neoplasia (AIN)2 rather than AIN3 (HR 1.79, 1.29-2.49), smaller lesions (HR 1.62, 1.11-2.36) and no persistent HPV16 (HR 1.72, 1.23-2.41). There was 1 progression to cancer (incidence 0.224, 95% CI .006-1.25 per 100 PY). CONCLUSION: These data strongly suggest that not all anal HSIL detected in screening requires treatment. Men with persistent HPV16 were less likely to clear HSIL and are more likely to benefit from effective HSIL treatments.

5.
Vaccine ; 38(5): 1186-1193, 2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-31767467

RESUMO

INTRODUCTION: Australia has recently implemented major changes in cervical cancer prevention policies including introduction of primary human papillomavirus (HPV) screening starting at age 25, and replacement of the quadrivalent HPV vaccine with the nonavalent vaccine in the national school-based program. We assessed the feasibility and utility of conducting HPV testing in residual clinical specimens submitted for routine Chlamydia trachomatis screening, as a means of tracking HPV vaccine program impact among young sexually active women. METHODS: De-identified residual specimens from women aged 16-24 years submitted for chlamydia testing were collected from three pathology laboratories in Victoria and New South Wales. Limited demographic information, and chlamydia test results were also collected. Patient identifiers were sent directly from the laboratories to the National HPV Vaccination Program Register, to obtain HPV vaccination histories. Samples underwent HPV genotyping using Seegene Anyplex II HPV 28 assay. RESULTS: Between April and July 2018, 362 residual samples were collected, the majority (60.2%) of which were cervical swabs. Demographic data and vaccination histories were received for 357 (98.6%) women (mean age 21.8, SD 2.0). Overall, 65.6% of women were fully vaccinated, 9.8% partially, and 24.7% unvaccinated. The majority (86.0%) resided in a major city, 35.9% were classified in the upper quintile of socioeconomic advantage and chlamydia positivity was 7.8%.The prevalence of quadrivalent vaccine-targeted types (HPV6/11/16/18) was 2.8% (1.5-5.1%) overall with no differences by vaccination status (p = 0.729). The prevalence of additional nonavalent vaccine-targeted types (HPV31/33/45/52/58) was 19.3% (15.6-23.8%). One or more oncogenic HPV types were detected in 46.8% (95% CI 41.6-52.0%) of women. CONCLUSIONS: HPV testing of residual chlamydia specimens provides a simple, feasible method for monitoring circulating genotypes. Applied on a larger scale this method can be utilised to obtain a timely assessment of nonavalent vaccine impact among young women not yet eligible for cervical screening.

6.
J Med Microbiol ; 2018 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30303481

RESUMO

PURPOSE: Chlamydia trachomatis is responsible for trachoma-associated blindness as well as the most common sexually transmitted bacterial infection worldwide, although the genovars for the former are typically A-C, whilst for the latter they are D-K and for the uncommon infection lymphogranuloma venereum they are L1-3. Nucleotide variations within the ompA gene facilitate the identification of C. trachomatis genovars. This study describes a colorimetric multiplex PCR/RLB typing assay (mPCR-RLB) directed to the VD2 region of the ompA gene for general C. trachomatis positivity and the identification of 14 individual C. trachomatis genovars. METHODOLOGY: The assay was validated by analysing 40 blinded samples that included reference strains of C. trachomatis genovars and other non-chlamydial micro-organisms that had been analysed previously using quantitative PCR (qPCR). Ninety clinical samples that had previously been found to be C. trachomatis-positive by qPCR were also evaluated using the mPCR-RLB assay. RESULTS: The mPCR-RLB assay showed 100 % agreement with the qPCR in the detection of C. trachomatis reference strains and no cross-reaction of non-chlamydial micro-organisms was observed. In the analysis of the chlamydial clinical samples, 97.8 % were C. trachomatis-positive by mPCR/RLB assay and there was a 96.6 % concordance with the qPCR at the group identification level and a 92.2 % concordance at the genovar level. CONCLUSION: The mPCR-RLB assay is a rapid and sensitive methodology for the identification of C. trachomatis genovars associated with urogenital infections, trachoma or lymphogranuloma venereum diseases that can be implemented in clinical settings, helping to identify reinfections and treatment failures and establish the appropriate treatment course.

7.
Oncol Lett ; 16(2): 2511-2516, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30013645

RESUMO

Certain variants of human papillomavirus (HPV)type 58 are associated with an increased risk of high grade squamous intraepithelial lesions and cervical cancer. However, little is known about the persistence of HPV58 E6/E7 variants in women with incident HPV58 infections. The aim of the present study was to evaluate the presence and persistence of HPV58 E6/E7 variants in 71 women with incident HPV58 infection throughout their follow-up. These women belonged to a cohort examined in a longitudinal study of 1,610 Colombian women, who were HPV-negative and had normal baseline cytology. E6/E7 DNA regions of HPV58-positive samples were amplified and sequenced using automated direct sequencing. A total of 639 samples were analyzed from the 71 women, and 117 samples (18.3%) were HPV58-positive. HPV58 E6/E7 variants were detected in 85.5% of the samples. The T307/A694/G744/A761 variant was identified in 88% of the samples, the T307/G744 variant was identified in 9% of samples and the T187/T307/A367/G744/G793/T798/A801/T840/C852 was identified in 3% of the samples. Overall, 50% of the HPV58 infections were present after 1 year of follow-up and all infections were cleared after 7 years. Women who had first sexual intercourse at >15 years of age had a lower clearance rate than those who had sexual intercourse for the first time at ≤15 years of age [hazard ratio (HR)=0.29; 95% confidence interval (CI)=0.09-0.92]. Likewise, parous women had a higher clearance rate than nulliparous women (HR=3.43, 95% CI=1.23-9.60). There was no difference in clearance rates between HPV58 E6/E7 variants. In conclusion, HPV58 variants were not associated with persistence of the infection in this group of women.

8.
Oncol Lett ; 15(1): 354-360, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29387223

RESUMO

Epidemiological information on telomerase activity (TA) and development of cervical lesions is scarce. A nested case-control study was carried out within a cohort of Colombian women tested for Human Papillomavirus (HPV). Measurement of TA was done in cervical scrapes of 25 women who developed High Grade Squamous Intraepithelial Lesion (HGSIL) during the first 6 years of follow-up and was compared with that of 104 control women who maintained normal cytology during the entire follow-up. TA was measured by a telomerase repeat amplification protocol-ELISA. TA and HPV infections were significantly more frequent in cases than in controls. Likewise, 68% of the cases were positive for both TA and HPV compared with only 7.7% of the controls (P<0.0001). Factors independently associated with increased odds of HGSIL included TA, high risk HPV (hrHPV) infections and multiple parities. When restricted to hrHPV positive women, TA was strongly associated with increased odds of HGSIL (adjusted odds ratio=37.94, 95% confidence interval, 1.64-678.1). In addition to an infection with hrHPV, TA appears to be a significant cofactor for HGSIL.

9.
Methods Mol Biol ; 1723: 167-189, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29344860

RESUMO

Human papillomavirus (HPV) is a nearly ubiquitous infectious organism. It is estimated that 80% of sexually active adults will be exposed to anogenital HPVs in their lifetime, and detection of multiple genotypes in an anogenital sample is common. Detection and genotyping of HPV is usually performed by DNA testing, and less frequently by mRNA testing. HPV genotype testing and characterization of DNA methylation patterns of HPV-related lesions can provide important biological, epidemiological, and potentially relevant clinical information in individuals and populations. The use of laser capture microdissection to isolate cells within a specific lesion allows for very precise molecular characterization and hence causal attribution. This chapter describes detailed protocols for the capture of lesion-specific tissue from formalin-fixed, paraffin-embedded (FFPE) biopsy tissue, and downstream DNA testing for lesion-specific HPV genotype and their methylation patterns.


Assuntos
Metilação de DNA , DNA Viral/genética , Microdissecção e Captura a Laser/métodos , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Lesões Intraepiteliais Escamosas Cervicais/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Separação Celular , Feminino , Genótipo , Humanos , Infecções por Papillomavirus/virologia , Inclusão em Parafina , Lesões Intraepiteliais Escamosas Cervicais/genética , Lesões Intraepiteliais Escamosas Cervicais/virologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia
10.
Cancer Genomics Proteomics ; 13(6): 483-491, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27807071

RESUMO

BACKGROUND: There exists limited information on the role of hTERT methylation, and its association with type-specific HPV infections in cervical cancer. MATERIALS AND METHODS: Eighty-seven frozen samples were analyzed for type-specific HPV infection using a GP5+/GP6+ PCR-RLB assay (RLB). hTERT DNA methylation analysis was performed using a newly developed PCR-RLB-hTERT. RESULTS: Ninety-three percent of samples were HPV-positive and fifteen different types were detected. hTERT methylation analysis of region 1 revealed no methylation in 78.8% of the samples and partial methylation in 21.2%. In region two, 68.2% showed no methylation and 31.8% showed a pattern of partial methylation. An association between the alpha 9 and alpha 7 species with a pattern of no methylation of hTERT in the region 1 was established (p=0.02 and p=0.03, respectively). CONCLUSION: Differences in patterns of methylation of the hTERT core promoter [region 1 (nt -208 to -1) and region 2 (nt +1 to +104) relative to first ATG] are related to the HPV species present.


Assuntos
Metilação de DNA/genética , Infecções por Papillomavirus/genética , Telomerase/genética , Neoplasias do Colo do Útero/genética , Feminino , Células HeLa , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/patogenicidade , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/patogenicidade , Humanos , Invasividade Neoplásica/genética , Infecções por Papillomavirus/classificação , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
11.
PLoS One ; 11(8): e0160673, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27529629

RESUMO

Incidence and mortality rates of anal cancer are increasing globally. More than 90% of anal squamous cell carcinomas (ASCC) are associated with human papillomavirus (HPV). Studies on HPV-related anogenital lesions have shown that patterns of methylation of viral and cellular DNA targets could potentially be developed as disease biomarkers. Lesion-specific DNA isolated from formalin-fixed paraffin-embedded (FFPE) tissues from existing or prospective patient cohorts may constitute a valuable resource for methylation analysis. However, low concentrations of DNA make these samples technically challenging to analyse using existing methods. We therefore set out to develop a sensitive and reproducible nested PCR-pyrosequencing based method to accurately quantify methylation at 10 CpG sites within the E2BS1, E2BS2,3,4 and Sp1 binding sites in the viral upstream regulatory region of HPV16 genome. Methylation analyses using primary and nested PCR-pyrosequencing on 52 FFPE tissue [26 paired whole tissue sections (WTS) and laser capture microdissected (LCM) tissues] from patients with anal squamous intraepithelial lesions was performed. Using nested PCR, methylation results were obtained for the E2BS1, E2BS2,3,4 and Sp1 binding sites in 86.4% of the WTS and 81.8% of the LCM samples. Methylation patterns were strongly correlated within median values of matched pairs of WTS and LCM sections, but overall methylation was higher in LCM samples at different CpG sites. High grade lesions showed low methylation levels in the E2BS1 and E2BS2 regions, with increased methylation detected in the E2BS,3,4/Sp1 regions, showing the highest methylation at CpG site 37. The method developed is highly sensitive in samples with low amounts of DNA and demonstrated to be suitable for archival samples. Our data shows a possible role of specific methylation in the HPV16 URR for detection of HSIL.


Assuntos
Neoplasias do Ânus/patologia , Ilhas de CpG/genética , Metilação de DNA , DNA Viral/genética , Papillomavirus Humano 16/genética , Microdissecção e Captura a Laser , Lesões Intraepiteliais Escamosas Cervicais/patologia , Neoplasias do Ânus/genética , Neoplasias do Ânus/virologia , Biópsia , Linhagem Celular Tumoral , Feminino , Papillomavirus Humano 16/fisiologia , Humanos , Gradação de Tumores , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Lesões Intraepiteliais Escamosas Cervicais/genética , Lesões Intraepiteliais Escamosas Cervicais/virologia
12.
Mol Clin Oncol ; 5(6): 792-796, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28101358

RESUMO

High hypoxic, glycolytic and acidosis metabolisms characterize cervical cancer tumors and have been described to be involved in chemoradioresistance mechanisms. Based on these observations, the present study assessed four selected novel biomarkers on the prognosis of locally advanced cervical carcinoma. A total of 66 patients with stage IIB/IIIB cervical cancer were retrospectively included. The protein expression levels of glucose transporter 1 (GLUT1), carbonic anhydrase 9 (CAIX) and hexokinase 1 (HKII) were investigated by immunohistochemistry on tumor biopsies, hemoglobin was measured and the disease outcome was monitored. A total of 53 patients (80.3%) presented a complete response. For these patients, the protein expression levels of GLUT1, CAIX and HKII were overexpressed. A significant difference was observed (P=0.0127) for hemoglobin levels (≤11 g/dl) in responsive compared with non-responsive patients. The expression of GLUT1 is associated with a lower rate of both overall and disease-free survival, with a trend of decreased risk of 1.1x and 1.5x, respectively. Co-expression of GLUT1 and HKII is associated with a decreased trend risk of 1.6x for overall survival. Patients with hemoglobin levels ≤11 g/dl had a 4.3-fold risk (P=0.02) in decreasing both to the rate of overall and disease-free survival. The presence of anemic hypoxia (hemoglobin ≤11 g/dl) and the expression of GLUT1 and/or HKII influence treatment response and are associated with a lower overall and disease-free survival. The present results demonstrated that these biomarkers may be used as predictive markers and suggested that these metabolic pathways can be used as potential novel therapeutic targets.

13.
BMJ Open ; 5(8): e008439, 2015 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-26310402

RESUMO

INTRODUCTION: Anal squamous cell carcinoma is preceded by persistent infection with high-risk human papillomavirus (HPV) and the cancer precursor, high-grade squamous intraepithelial lesion (HSIL). Detection of specific HPV genotypes and HPV-related biomarkers may be an option for primary anal screening. However, more data on the natural history of HPV-related anal lesions are required. The outcomes from this study will enhance our understanding of the clinical and biological behaviour of HPV-related anal lesions and inform the development of future HPV genotype and/or biomarker screening tests. METHODS AND ANALYSIS: HIV-negative and HIV-positive men who have sex with men, aged 35 years and over, recruited from community-based settings in Sydney, Australia, attend 6 clinic visits over 3 years. At the first 5 visits, participants undergo a digital anorectal examination, an anal swab for HPV genotyping and anal cytology, and high-resolution anoscopy with directed biopsy of any visible abnormalities that are suggestive of any abnormality suspicious of SIL. Tissue sections from participants diagnosed with histologically confirmed HSIL at the baseline clinic visit will undergo laser capture microdissection, HPV detection and genotyping, and quantitation of CpG methylation in baseline and follow-up biopsies. Histological and cytological findings in combination with HPV genotyping data will be used to identify persistent HSIL. HSIL will be stratified as non-persistent and persistent based on their status at 12 months. The performance of HPV genotype and methylation status in predicting disease persistence at 12 months will be assessed, along with associations with HIV status and other covariates such as age. ETHICS AND DISSEMINATION: The St Vincent's Hospital Ethics Committee granted ethics approval for the study. Written informed consent is obtained from all individuals before any study-specific procedures are performed. Findings from this study will be disseminated to participants and the community through study newsletters, and through peer-reviewed publications and international conferences.


Assuntos
Neoplasias do Ânus/diagnóstico , Biomarcadores/análise , Microdissecção e Captura a Laser/métodos , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Adulto , Canal Anal/patologia , Canal Anal/virologia , Austrália , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Metilação de DNA , Progressão da Doença , Genótipo , Soropositividade para HIV/complicações , Homossexualidade Masculina , Humanos , Masculino , Pessoa de Meia-Idade
14.
J Clin Virol ; 68: 89-93, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26071344

RESUMO

BACKGROUND: Hepatitis C virus (HCV) infection is a significant global health issue because it is widespread and persistent and can cause serious liver diseases. OBJECTIVES: The aim of this study is to estimate HCV prevalence in women from the general population in different geographical areas worldwide and to assess the potential role of sexual behaviour in the virus transmission. STUDY DESIGN: Each participating centre recruited a random sample of women from the general population aged from less than 20 to more than 75 years. The study included 8130 women from 8 countries with information on sociodemographic factors, reproductive and sexual behaviour, smoking habit and HPV DNA through individual interviews. A blood sample was also collected to perform serological tests. We estimated the prevalence ratios associated to HCV to evaluate the effect of sexual behaviour in viral transmission. RESULTS: Women were reactive to a minimum of two HCV antigens, including at least one non structural protein were considered as positive (33% of the samples were classified as positive, 40% as negative, and 27% as indeterminate (N=402), that were considered as not positive). The age-adjusted HCV seroprevalence varied significantly by regions (0.3% in Argentina to 21.1% in Nigeria). We found no association between HCV prevalence and age, educational level, smoking habit and any of the available variables for sexual behaviour and reproductive history. CONCLUSIONS: This large study showed heterogeneous distribution of HCV seroprevalence in female and provides evidence of the null impact of sexual behaviour in HCV transmission.


Assuntos
Hepatite C/epidemiologia , Comportamento Sexual , Doenças Virais Sexualmente Transmissíveis/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Saúde Global , Hepatite C/transmissão , Antígenos da Hepatite C/sangue , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Estudos Soroepidemiológicos , Doenças Virais Sexualmente Transmissíveis/transmissão , Adulto Jovem
15.
Rev. colomb. cancerol ; 17(3): 103-110, jul.-sep. 2013. ilus, tab
Artigo em Inglês | LILACS | ID: lil-727561

RESUMO

Objective: To analyze whether the immune response to HPV-16, -18, -31, -45 and -58 capsids in women vaccinated with the quadrivalent vaccine induces cross-reactivity against other HPV virus-like particles (VLPs). Methods: A total of 88 women aged between 18 and 27 years attending the HPV clinic at the Instituto Nacional de Cancerología were enrolled and vaccinated against HPV. Follow-up visits were scheduled at months 7, 12, and 24. Samples were collected for cytology, HPV-DNA typing, and detection of HPV antibodies. IgG antibodies were measured by ELISA using HPV-16, -18, -31, -45, and -58 VLPs. HPV-DNA detection was done by GP5+/GP6+PCR-ELISA and HPV typing was performed by Reverse Line-Blot assay. Results: Pre-vaccination, the seroprevalence of HPV-16, -18, -31, -45, and -58 was 39%, 31.7%, 15.9%, 31.7%, and 23.2%, respectively. One month post-vaccination, the seroprevalence increased close to 100% for all types. At month 24, this response was maintained only for HPV-16 and -18. For HPV-31, -45 and -58, the seroprevalence decreased to below 50%. The prevalence of HPV DNA types 16, 18 and 58 before vaccination was little changed 1 month after vaccination. No new infections were observed at 24 months. For HPV-16 and -18 related types, no differences were observed before vaccination and at month 24. For other high-risk HPV types, the prevalence increased 18 months post-vaccination (15.5%) compared with pre-vaccination (9.8%). Conclusion: Immune response to all HPV types increased after vaccination, but this increase was maintained only for HPV-16 and -18. These results suggest a possible cross-reactivity against HPV types 31, 45 and 58, but this cross-reactivity wanes with time. © 2012 Instituto Nacional de Cancerología. Publicado por Elsevier España, S.L. Todos los derechos reservados.


Objetivo: Analizar si la respuesta inmune hacia las cápsides del VPH tipos 16, 18, 31, 45 y 58 en mujeres que recibieron la vacuna tetravalente induce reactividad cruzada hacia otros tipos virales. Métodos: Ochenta y ocho mujeres entre 18 y 27 años, asistentes al Grupo VPH del Instituto Nacional de Cancerología, recibieron la vacuna de VPH. Visitas de seguimiento en los meses 7, 12 y 24. Se tomaron muestras para prueba de Papanicolaou, tipificación de VPH y detección de anticuerpos. Los anticuerpos se detectaron por ELISA, usando VLP-VPH. La detección del ADN-VPH se realizó por Reverse Line Blot. Resultados: Prevacunación, la seroprevalencia de VPH tipos 16, 18, 31, 45 y 58 fue de 39, 31,7, 15,9, 31,7 y 23,2%, respectivamente. Al mes 7 aumentó cerca del 100% para todos los tipos. Al mes 24 esta respuesta se mantuvo para VPH tipos 16 y 18. Para VPH tipos 31, 45 y 58 disminuyó por debajo del 50%. La prevalencia de ADN-VPH tipos 16, 18 y 58 tuvo poca variación antes y un mes después de la vacunación. Al mes 24, no se observaron nuevas infecciones. Para VPH tipos 16 y 18, no se observaron diferencias antes ni al mes 24. En otros tipos de HR-VPH aumentó la prevalencia al mes 24 (15,5%), comparada con la prevacunación (9,8%). Conclusión: Se observó un aumento de la respuesta inmune a todos los tipos de VPH después de la vacunación, pero esta se mantuvo solamente para los VPH tipos 16 y 18. Los resultados sugieren una posible reactividad cruzada contra VPH tipos 31, 45 y 58. Sin embargo, esta reactividad cruzada disminuye con el tiempo.


Assuntos
Humanos , Feminino , Adolescente , Adulto , Papiloma , Estudos Soroepidemiológicos , Prevalência , Vacinação , Ensaio de Imunoadsorção Enzimática , Papillomavirus Humano 16 , Papillomavirus Humano 31
16.
Rev. colomb. cancerol ; 17(3): 93-102, jul.-sep. 2013. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-727560

RESUMO

Objetivo: Describir las barreras para la implementación de un programa de tamización para cáncer de cuello uterino basado en la prueba de virus del papiloma humano (VPH) en Colombia. Métodos: Se aplicó el modelo de planeación Precede-Procede en cuatro municipios de Cundinamarca y dos de Boyacá; se realizó análisis de fuentes secundarias y primarias obtenidas de 74 encuestas a instituciones de salud, 18 grupos focales (GF), con líderes comunitarios, gerentes y profesionales de la salud y 12 entrevistas (autoridades locales). Resultados: Se identificaron las siguientes barreras: 1) la infección por VPH se asocia a una enfermedad venérea; 2) barreras epidemiológicas: la ausencia de un adecuado registro de diagnóstico definitivo de lesiones preneoplásicas; 3) barreras del comportamiento del sistema, tales como la no centralización de la lectura de citologías, laboratorios no habilitados que prestan servicios y la no estandarización de la colposcopia ni el tratamiento; 4) barreras educacionales: los profesionales de la salud sobreestiman la sensibilidad de la citología y les preocupa demasiado la infección por VPH en mujeres menores de 30 años, y 5) barreras administrativas de acceso a la colposcopia y a la biopsia de lesiones preneoplásicas. Conclusiones: Colombia presenta barreras que impiden el funcionamiento de un programa organizado de tamización, las cuales hacen difícil lograr los objetivos esperados con el cambio tecnológico de citología a pruebas moleculares.


Objective: To identify the barriers for the implementation of a cervical cancer-screening program based on human papillomavirus (HPV) testing in Colombia. Methods: The Precede-Proceed model was applied in four municipalities of Cundinamarca and two of Boyacá. Secondary and primary data were analyzed from 74 institutional surveys, 18 focus groups (with community leaders and health professionals), and 12 interviews (health authorities). Results: The most relevant barriers were identifi ed as follows: 1) Social barriers: in Duitama, the municipality with a religious tradition, HPV infection is represented as a venereal disease. 2) Epidemiological barrier: the absence of a register for defi nitive diagnosis of pre-neoplasic lesions. 3) Behavioral barriers: Pap smear laboratories are not centralized, some are not accredited and colposcopies are not standardized. 4) Health professionals overestimate Papsmear sensitivity and they are over worried about HPV infection among women younger than 30 years. 5) Administrative barriers: positive screened women need to have an authorization from Health Insurance Enterprises in order to access the diagnosis and treatment of cervical lesions. Conclusions: Colombia presents barriers to the operation of an organized screening program that make it diffi cult to achieve the expected objectives with the technological change from the use of cytology to molecular testing.


Assuntos
Humanos , Feminino , Terapêutica , Neoplasias do Colo do Útero , Infecções por Papillomavirus , Métodos , Programas de Rastreamento , Seguro Saúde
17.
Rev. colomb. cancerol ; 16(1): 40-48, mar. 2012. graf
Artigo em Espanhol | LILACS | ID: lil-662981

RESUMO

Objetivo: Analizar la presencia y persistencia de variantes en E6/E7/VPH 58 en muestras de mujeres con infecciones prevalentes por VPH 58, con citología normal, que pertenecen a la cohorte de Bogotá, Colombia. Métodos: Se utilizaron cepillados cervicales de 34 mujeres VPH 58, con citología normal, pertenecientes a la línea de base de la cohorte, con su respectivo seguimiento. Se amplificó la región E6/E7 del VPH 58 usando los iniciadores E6F1-E7R1 y los iniciadores E7P1-E7P2. Para el análisis de las variantes se utilizó la técnica de secuencia automática directa. La secuencia referencia del VPH 58 se utilizó para comparar las secuencias obtenidas. Resultados: En 27/34 muestras se lograron detectar variantes de E6/E7 de VPH 58. En total, se detectaron cinco variantes diferentes, dos de ellas nunca antes reportadas (A169/T307/A694/G744/A761 y T307/A694/G744/A761/G763). Los análisis de eliminación mostraron que el 75% de las variantes se habían eliminado antes de los dos años de seguimiento, y todas las variantes ya se habían eliminado a los seis años de seguimiento. Conclusiones: Dos nuevas variantes se reportaron a escala mundial de gran relevancia en los ámbitos filogenético y epidemiológico.


Objective: To analyze the presence and persistence of E6/E7 HPV58 variations in women with prevalent HPV 58 infection, with normal cytology, who belong to the Bogotá, Colombia cohort. Methods: Cervical cytobrush was used on 34 HPV58 women, with normal cytology, who are part of the cohort base line; respective follow was performed. The HPV58 E67/E7 region was broadened by using E6F1-E7R1 and E7P1-E7P2 indicators. Variation analysis was carried out with automatic direct sequencing. HPV58 sequence reference was used to compare the sequences that had been obtained. Results: In 27/34 samples, E6/E7 variations of HPV58 were successfully detected. A total of five different variations were detected, two of which had never been reported before (A169/T307/A694/G744/A761 and T307/A694/G744/A761/G763). Elimination analysis revealed that 75% of variations had been eliminated within two years of follow up, and that all variation had been eliminated at the end of six years of follow up. Conclusions: Two new variations of universal phylogenetic and epidemiologic noteworthiness were reported.


Assuntos
Humanos , Feminino , Adolescente , Adulto , Idoso , Estudos de Coortes , Colo do Útero/citologia , Estudos Epidemiológicos , Estudos Transversais/classificação , Estudos Transversais/estatística & dados numéricos , Estudos Transversais/métodos , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/genética , Neoplasias do Colo do Útero/classificação , Neoplasias do Colo do Útero/epidemiologia , Colômbia/epidemiologia
18.
Rev. colomb. cancerol ; 16(1): 27-39, mar. 2012. tab
Artigo em Espanhol | LILACS | ID: lil-662987

RESUMO

Objetivo: Describir la AT y la infección por VPH en el seguimiento de mujeres que pertenecen a la cohorte de Bogotá. Métodos: Se analizaron 79 muestras del seguimiento de 25 mujeres que desarrollaron LEI-AG y 149 muestras del seguimiento de 34 mujeres con citología normal. La detección del VPH se realizó usando PCR-EIA GP5+/GP6+ y RLB. La AT se midió mediante TRAP-ELISA. Resultados: El análisis mostró que de los 25 casos, 8 fueron casos prevalentes (ingresaron al estudio con la LEI-AG) y los 17 casos restantes fueron incidentes (la lesión se detectó durante el seguimiento). De estas 17 mujeres, 12 (70,5%) presentaron AT y VPH al momento del diagnóstico o en una visita previa, con VPH de alto riesgo (VPH-AR), principalmente de la especie α-9. Tres mujeres (17,7%) mostraron infecciones transitorias por VPH y 2 (11,8%) no tuvieron VPH o AT al diagnóstico. El seguimiento de la mujeres con citología normal mostró que solo ocho mujeres tuvieron VPH y AT al mismo tiempo (23,5%), 21/34 mujeres (61,8%) tuvieron eventos transitorios de VPH durante el seguimiento y 5 (14,7%) no tuvieron VPH durante todo el seguimiento. Conclusiones: Detectar AT e infección por VPH-AR al mismo tiempo parecen predecir el riesgo de LEI-AG.


Objective: To describe telomerase activity (TA) and HPV infection in follow up of women in the Bogotá cohort. Methods: Analysis was carried out on 79 follow up samples from 25 women who developed LEI-AG, and 149 follow up samples from 34 women with normal cytology. HPV detection was made with PCR-EIA GP5+/GP6+ and RLB. TA was measured with TRAP-ELISA. Results: Analysis revealed that out of the 25 cases, 8 were prevalent (enrolled in the study with LEI-AG), and the remaining 17 incidental (lesion was detected during follow up). Among these 17 women, 12 (70.5%) had, at diagnosis or during a previous checkup, TA and high-risk HPV (HPV-AR), primarily type α-9. Three women (17.7%) had transitory HPV infections, and 2 (11.8%) had neither HPV nor TA at diagnosis. Follow up on women with normal cytology revealed that only eight women (23.5%) had HPV and TA at the same time, 21/34 women (61.8%) had transitory HPV event during follow up, and 5 (14.7%) had no HPV during entirety of follow up. Conclusions: Detection of TA and simultaneous HPV-AR infection apparently predicts LEI-AR risk.


Assuntos
Humanos , Feminino , Adolescente , Adulto Jovem , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Seguimentos , Infecções por Papillomavirus/classificação , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/genética , Telomerase , Biologia Celular/instrumentação , Colômbia/epidemiologia , Ensaio de Imunoadsorção Enzimática/classificação , Ensaio de Imunoadsorção Enzimática/métodos
19.
Virology ; 410(1): 201-15, 2011 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-21130481

RESUMO

Reports on taxonomic identification of E6/HPV 16 variants, don't have a worldwide, updated and unified criterion for clustering and nomenclature. Our aim was to update the existing criterion and propose a new one for clustering and nomenclature for E6/HPV 16 molecular variants based on the descriptive and comparative analyses of nucleotide sequences. A systematic search of the publications between 1991 and 2010 was carried out in PUBMED and manually. 240 E6/HPV 16 variants were identified. 157 were classified as European (E), 24 as Asian (As), 14 as Asian American (AA), 11 as North American 1 (NA 1), 19 as African 1 (Af 1) and 15 as African 2 (Af 2). Three classes were determined for the E, 3 each for the As, Af 2 and AA branches, 4 classes for the NA 1 and 6 for the Af 1 branch. This study reports our results and proposes an updated criterion for clustering and nomenclature that will be useful for E6 variant identification.


Assuntos
Variação Genética , Papillomavirus Humano 16/classificação , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Terminologia como Assunto , Sequência de Bases , Análise por Conglomerados , Feminino , Regulação Viral da Expressão Gênica/fisiologia , Saúde Global , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/metabolismo , Humanos , Dados de Sequência Molecular , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia
20.
Rev. colomb. cancerol ; 14(4): 199-209, dic. 2010. tab, graf
Artigo em Inglês | LILACS | ID: lil-664803

RESUMO

Objective: To analyze the role of Human Papillomavirus (HPV) and other risk factors in the regression of cervical lesions in women from the Bogotá Cohort. Methods: 200 HPV positive women with abnormal cytology were included for regression analysis. The time of lesion regression was modeled using methods for interval censored survival time data. Median duration of total follow-up was 9 years. Results: 80 (40%) women were diagnosed with Atypical Squamous Cells of Undetermined Significance (ASCUS) or Atypical Glandular Cells of Undetermined Significance (AGUS) while 120 (60%) were diagnosed with Low Grade Squamous Intra-epithelial Lesions (LSIL). Globally, 40% of the lesions were still present at first year of follow up, while 1.5% was still present at 5 year check-up. The multivariate model showed similar regression rates for lesions in women with ASCUS/AGUS and women with LSIL (HR= 0.82, 95% CI 0.59-1.12). Women infected with HR HPV types and those with mixed infections had lower regression rates for lesions than did women infected with LR types (HR=0.526, 95% CI 0.33-0.84, for HR types and HR=0.378, 95% CI 0.20-0.69, for mixed infections). Furthermore, women over 30 years had a higher lesion regression rate than did women under 30 years (HR= 1.53, 95% CI 1.03-2.27). The study showed that the median time for lesion regression was 9 months while the median time for HPV clearance was 12 months. Conclusions: In the studied population, the type of infection and the age of the women are critical factors for the regression of cervical lesions.


Objetivo: Analizar el papel del virus del papiloma humano (VPH) y otros factores en la regresión de lesiones del cuello del útero en mujeres de la cohorte de Bogotá, Colombia. Métodos: El tiempo medio de seguimiento fue nueve años. Se incluyeron 200 mujeres VPH positivas con citología anormal. El tiempo de regresión de lesión fue modelado mediante análisis de supervivencia censurando por intervalos. Resultados: 80 mujeres (40%) tuvieron células escamosas atípicas de significado indeterminado (ASCUS) o células glandulares atípicas de significado indeterminado (AGUS) y 120 (60%) tuvieron lesiones escamosas intraepiteliales de bajo grado (LEI-BG). El 40% de las lesiones estaban presentes en el primer año de seguimiento, mientras que el 1,5% aún estaba a los cinco años. Se observaron tasas similares de regresión para ASCUS/AGUS y LEI-BG (HR=0,82, IC 95% 0,59-1,12). Mujeres infectadas con VPH de alto riesgo y aquéllas con infecciones mixtas tuvieron tasas inferiores de regresión de las lesiones que las mujeres con VPH de bajo riesgo (HR=0,526, IC 95% 0,33-0,84, para los VPH de alto riesgo, y HR=0,378, IC 95% 0,20-0,69, para las infecciones mixtas). Las mujeres mayores de 30 años tuvieron una mayor tasa de regresión de lesiones que las menores de 30 (HR= 1,53, IC 95% 1,03-2,27). El tiempo medio de regresión de las lesiones fue 9 meses, y el tiempo medio para la eliminación del VPH fue 12 meses. Conclusiones: En la población estudiada, el tipo de infección y la edad de las mujeres son factores críticos para la regresión de lesiones cervicales.


Assuntos
Humanos , Adulto , Feminino , Idoso , Estudos de Coortes , Infecções por Papillomavirus , Análise de Sobrevida , Técnicas Citológicas/métodos , Carcinoma de Células Escamosas , Colômbia
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