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1.
BMC Infect Dis ; 24(1): 539, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38811877

ABSTRACT

BACKGROUND: Cervical cancer (CC) is a significant global public health concern, particularly in developing countries such as Colombia. The main risk factor involves high-risk HPV types (HR-HPV) infection, coupled with population-specific variables. The Caribbean region in Colombia lacks research on HR-HPV-type frequencies. Therefore, this study aims to establish the prevalence of type-specific HR-HPV and its association with sociodemographic factors among women undergoing cervical cytology screening. METHODS: A cross-sectional study involving voluntary women who provided informed consent and completed a questionnaire capturing sociodemographic, clinical, and sexual behavior information was conducted. All participants underwent cervical cytology and molecular analysis. Generic HPV detection employed three simultaneous PCRs (GP5+/6+, MY09/11, and PU1R/2 M), and positive samples were genotyped using the Optiplex HPV Genotyping kit. The analysis encompassed the 12 types of high-risk HPV (HR-HPV-16,-18,-31,-33,-35,-39,-45,-51,-52,-56,-58, and - 59). Frequencies were reported based on geographic subregions within the Córdoba department, and disparities were made between single and multiple infections. Sociodemographic and clinical variables were subjected to ordinal logistic regression, with statistical significance at a p-value < 0.05. The statistical analyses utilized STATA 14® and R-Core Team-software. RESULTS: We included 450 women, mean age 40 (SD±11.44). PCR analysis revealed 43% HPV-positive (n=192). GP5+/6+ detected the most positives at 26% (n=119), followed by PU1R/2 M at 22% (n = 100) and MY09/11 at 15% (n=69). Multiple infections occurred in 87.3% (n=142), primarily 2 to 4 types (47.37%, n=90). Dominant types were HPV-18 (15.6%, n=61), HPV-16 (14.9%, n=58), HPV-31 (13.0%, n = 51), and HPV-45 (11.5%, n=45). Logistic regression identified age above 60 as a risk for concurrent multiple types (OR=6.10; 95% CI 1.18-31.63). Menopause was protective (OR=0.31; 95% CI 0.11-0.89). CONCLUSIONS: Our study reveals a notable prevalence of multiple (2-4) high-risk HPV infections among adult women engaged in CC detection initiatives. Predominantly, α7 species constitute the prevalent HR-viral types, with the Medio Sinú subregion showing elevated prevalence. Menopausal status confers protection against diverse HR-HPV infections. Nevertheless, advancing age, particularly beyond 60 years, is linked to an increased susceptibility to simultaneous infections by multiple HPV-types.


Subject(s)
Early Detection of Cancer , Papillomavirus Infections , Uterine Cervical Neoplasms , Humans , Female , Adult , Papillomavirus Infections/epidemiology , Papillomavirus Infections/virology , Papillomavirus Infections/diagnosis , Colombia/epidemiology , Cross-Sectional Studies , Uterine Cervical Neoplasms/virology , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/diagnosis , Middle Aged , Prevalence , Papillomaviridae/genetics , Papillomaviridae/isolation & purification , Papillomaviridae/classification , Genotype , Young Adult , Risk Factors , Aged , Alphapapillomavirus/genetics , Alphapapillomavirus/isolation & purification , Alphapapillomavirus/classification , Caribbean Region/epidemiology
2.
Sci Rep ; 11(1): 19924, 2021 10 07.
Article in English | MEDLINE | ID: mdl-34620929

ABSTRACT

The prevalence of HPV infection and its relationship with other sexually transmitted infections was analyzed in a cohort of 117 male partners of infertile couples from Cordoba, Argentina. Semen samples and urethral swabs were obtained and the infection with HPV, Chlamydia trachomatis, HSV1, HSV2, Mycoplasma hominis and Ureaplasma urealyticum was analyzed. A prevalence of HPV infection of 27.4% was found. Interestingly, infections by exclusively low risk HPV genotypes or high/intermediate risk HPV genotypes were present in 64.5% and 22.6% of cases, respectively. Low risk-HPV6 was the most frequently detected genotype. Remarkably, HPV and C. trachomatis infections were significantly associated to each other (OR: 11.55, 95% CI 1.14-117.06). No significant differences in sperm quality were found between HPV-positive and HPV-negative patients indicating that HPV male urogenital infection does not impair sperm quality. Our results show a high prevalence of HPV urogenital infection among male partners of infertile couples, and that HPV and C. trachomatis infections are reciprocal risk factors of their co-infection. Moreover, our results suggest that men constitute a reservoir for continued transmission of C. trachomatis and HPV to women highlighting the need for routine screening for these two pathogens in male partners of infertile couples.


Subject(s)
Alphapapillomavirus , Chlamydia Infections/epidemiology , Chlamydia Infections/microbiology , Chlamydia trachomatis , Infertility, Male/epidemiology , Warts/epidemiology , Warts/virology , Adult , Alphapapillomavirus/classification , Alphapapillomavirus/genetics , Coinfection , Disease Susceptibility , Female , Genotype , Humans , Infertility, Male/diagnosis , Infertility, Male/etiology , Male , Middle Aged , Prevalence , Public Health Surveillance , Semen
3.
Diagn Cytopathol ; 48(11): 1021-1026, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32496006

ABSTRACT

OBJECTIVES: To explore male human papillomavirus (HPV) contemporary genotyping epidemiology and correlations to peniscopy, cytology, and histopatology. METHODS: Medical records of patients who had been submitted to HPV infection screening with genotyping, peniscopy, cytology, and histopathology in a period of 2 years were reviewed. Frequency analysis and correlations between the diagnostic tools were established. RESULTS: Genotype of 1132 men resulted in 69.2% (784) positivity for HPV DNA, 78% classified as high risk of oncogenesis. Co-infections occurred in 429 (54.7%) and the most frequently identified types were HPV-6, HPV-42, and HPV-16, in 133 (17%), 94 (12%), and 86 (11%) patients, respectively. Positive/negative predictive values of peniscopy, cytology, and histopathology were 83/31%, 92/32%, and 87/33%, respectively. As a result, though significant, the correlations between genotype and non-molecular tests were poor. CONCLUSIONS: In the current contemporary representative male cohort, over two thirds are positive for human HPV DNA, 78% of high risk and with over half co-infections. Though significant, its correlation with non-molecular tests is poor and while the positive predictive values of peniscopy, cytology, and histopatology are between 83% and 92%, their negative predictive values are as low as 31% to 33%.


Subject(s)
Alphapapillomavirus/isolation & purification , Human papillomavirus 16/genetics , Human papillomavirus 6/genetics , Papillomavirus Infections/diagnosis , Papillomavirus Infections/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Alphapapillomavirus/classification , Alphapapillomavirus/genetics , Carcinoma in Situ/virology , Child , Condylomata Acuminata/virology , Cytodiagnosis , DNA, Viral/genetics , Genotype , Human papillomavirus 16/isolation & purification , Human papillomavirus 6/isolation & purification , Humans , Male , Mass Screening , Middle Aged , Papillomavirus Infections/pathology , Penile Neoplasms/virology , Penis/virology , Sexual Behavior , Young Adult
4.
Papillomavirus Res ; 9: 100199, 2020 06.
Article in English | MEDLINE | ID: mdl-32464335

ABSTRACT

INTRODUCTION: Oral human papillomavirus (HPV) attributable oropharyngeal cancers are on the rise in many countries. Oral HPV infections among healthy individuals are commonly detected using oral gargle samples. However, the optimal method for HPV genotyping oral gargle specimens in research studies has not been previously evaluated. MATERIALS AND METHODS: Oral gargle samples from 1455 HPV Infection in Men (HIM) study participants were HPV genotyped using two different methods: Linear Array and the SPF10 PCR-DEIA-LiPA25. The sensitivity of the two tests for detecting individual HPV types and grouped HPV types, high-risk HPV, low-risk HPV, grouped 4-HPV-vaccine types, and grouped 9-HPV-vaccine-types, and the degree of concordance between the two tests was assessed. We also examined whether socio-demographic-behavioral factors were associated with concordance between the two assays. RESULTS: The sensitivity of SPF10 PCR-DEIA-LiPA25 was higher than Linear Array, with the exception of HPV 70, for the detection of oral HPV. The prevalence ratio of SPF10 PCR-DEIA-LiPA25 to Linear Array varied between 1.0 and 9.0 for individual HPV genotypes, excluding HPV 70, and between 3.8 and 4.4 for grouped 4-valent and 9-valent HPV vaccine types, respectively. There was no association between socio-demographic-behavioral factors and discordance in results between the two tests for oral HPV 16 detection. DISCUSSION: SPF10 PCR-DEIA-LiPA25 was more sensitive than Linear Array for detecting HPV in oral gargle samples. Given the growing importance of detecting oral HPV infection for research studies of oral HPV natural history and vaccine effectiveness evaluation, we recommend using methods with higher sensitivity such as SPF10 PCR-DEIA-LiPA25 for detecting HPV in oral gargle samples.


Subject(s)
Alphapapillomavirus/isolation & purification , Mouth/virology , Oligonucleotide Array Sequence Analysis/methods , Papillomavirus Infections/diagnosis , Papillomavirus Infections/epidemiology , Adolescent , Adult , Aged , Alphapapillomavirus/classification , Brazil/epidemiology , DNA, Viral/genetics , Genotype , Genotyping Techniques , Humans , Male , Mexico/epidemiology , Middle Aged , Oropharyngeal Neoplasms/virology , Papillomavirus Infections/virology , Polymerase Chain Reaction , Prevalence , Prospective Studies , Sensitivity and Specificity , United States/epidemiology , Young Adult
5.
Vaccine ; 38(13): 2816-2826, 2020 03 17.
Article in English | MEDLINE | ID: mdl-32088019

ABSTRACT

BACKGROUND: Incidence and mortality of human papillomavirus (HPV)-related cancers differs geographically, with high rates in Caribbean countries. Seroepidemiological data provide information on lifetime cumulative HPV exposure and contributing risk factors, but has not been available yet for Caribbean Netherlands (CN), comprising the islands Bonaire, St. Eustatius and Saba. Therefore, a cross-sectional population-based serosurveillance study was performed in this (recently girls-only HPV-vaccinated) population in 2017. METHODS: Blood samples from participants (n = 1,823, 0-90 years) were tested for seven high-risk (hr)-HPV-specific IgG-antibodies using a VLP-based multiplex-immunoassay. Risk factors for HPV-seropositivity were analysed among persons unvaccinated aged ≥ 15 years who ever had sex (n = 1,080). RESULTS: Among unvaccinated individuals aged ≥ 15 years, overall seropositivity was high (34%), with over half of them being seropositive for ≥ 2 hr-HPV types, and HPV16 and 52 being most prevalent (13%). Seroprevalence was substantial higher in unvaccinated women (51%) than men (18%), predominantly peaking in women aged 20-59 years, and was highest on St. Eustatius (38%). Besides age and sex, sexual risk factors were associated with HPV-seropositivity. CONCLUSIONS: In accordance with the Caribbean region, seroprevalence of multiple hr-HPV types was high in CN. These data corroborate the decision regarding introduction of a sex-neutral HPV-vaccination program and the relevance for considering a population-based cervical cancer screening program.


Subject(s)
Alphapapillomavirus/classification , Papillomavirus Infections , Papillomavirus Vaccines , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , Caribbean Netherlands , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Immunoglobulin G/blood , Infant , Infant, Newborn , Male , Middle Aged , Papillomavirus Infections/blood , Papillomavirus Infections/epidemiology , Risk Factors , Seroepidemiologic Studies , Young Adult
6.
Infect Genet Evol ; 67: 210-221, 2019 01.
Article in English | MEDLINE | ID: mdl-30458293

ABSTRACT

Members of the Alphapapillomavirus genus are causative agents for cervix cancer and benign lesions in humans. These viruses are classified according to sequence similarities in their L1 region. Yet, viral carcinogenicity has been associated with variations in the proteins encoded by the E6 and E7 genes. In order to relate evolutionary history with origin of carcinogenicity, we performed phylogenetic reconstructions using both nucleotide and predicted amino acid sequences of the L1, E6 and E7 genes. Whilst phylogenetic analysis of L1 reconstructed genus evolutionary history, phylogenies based on E6 and E7 proteins support the idea that mutations at amino acids S/Tx [V/L] (E6) and LxCxE (E7) might be responsible for carcinogenic potential. These findings indicate that virulence within Alphapapillomavirus have appeared multiple times during evolution. Our results reveal that oncogenic potential is not a monophyletic clade-specific adaptation but might be the result of positive selection on random mutations occurring on proteins involved in host infection during viral diversification.


Subject(s)
Alphapapillomavirus/classification , Alphapapillomavirus/genetics , Cell Transformation, Viral , Evolution, Molecular , Oncogene Proteins, Viral/genetics , Papillomavirus E7 Proteins/genetics , Phylogeny , Viral Tropism , Amino Acid Sequence , Base Sequence , Computational Biology/methods , Conserved Sequence , Female , Genotype , Humans , Mutation , Oncogene Proteins, Viral/chemistry , Papillomavirus E7 Proteins/chemistry , Uterine Cervical Neoplasms/etiology
7.
Epidemiol Infect ; 146(9): 1184-1193, 2018 07.
Article in English | MEDLINE | ID: mdl-29781414

ABSTRACT

Persistent infection with high-risk human papillomavirus (HPV) is the main cause of cervical cancer and the prevalence of HPV types varies depending on the geographic region. Therefore, this study assessed the prevalence of HPV types in women with cervical lesions from Sergipe state, Northeastern Brazil. A cross-sectional study was conducted in women with cervical lesions from March to December 2014. These lesions were investigated by PCR and HPV types were identified by DNA sequencing. 432 patients were included, of which 337 patients tested positive for HPV. Eighteen different HPV types were detected, and high-risk HPV types were detected in 69.2%. HPV 16 (63.4%) was the most prevalent HPV type found, followed by HPV 66 (4.6%), HPV 18 (1.6%) and HPV 45 (1.4%). These results highlight the importance of the high prevalence of HPV 66, which is a possibly carcinogenic virus type not covered by the available vaccines. The prevalence of HPV 16 was high in the studied population, reaffirming the importance of young vaccination. However, the high prevalence of HPV 66 found in this study shows the importance of monitoring the diversity of HPV types in different populations and geographic regions to better understand the impacts of current HPV vaccines.


Subject(s)
Alphapapillomavirus/classification , Papillomavirus Infections/virology , Uterine Cervical Neoplasms/virology , Adolescent , Adult , Aged , Alphapapillomavirus/genetics , Alphapapillomavirus/isolation & purification , Brazil/epidemiology , Cross-Sectional Studies , DNA, Viral/analysis , Female , Humans , Middle Aged , Papillomavirus Infections/complications , Papillomavirus Infections/diagnosis , Papillomavirus Infections/epidemiology , Prevalence , Risk Assessment , Risk Factors , Young Adult
8.
Arch Virol ; 163(4): 925-935, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29299683

ABSTRACT

The incidence of anal cancer has been rising, especially in HIV+ patients and has been associated with HPV infection. HIV+ patients are more at risk of HPV coinfection and are seven times more likely to have persistent HPV infection; moreover, HIV+ men have an increased risk of developing anal cancer compared to HIV+ women. The development of screening strategies for the detection of HPV in HIV+ men is of major importance; however, there is not enough information about the HPV genotypes and variants that are colonizing the anal epithelia of HIV+ men in diverse geographical regions. Therefore, this work was aimed at identifying HPV genotypes present in the anal epithelium of HIV+ men who have sex with men (MSM), with or without anal lesions (n = 75). For HPV genotyping, two approaches were performed: Linear Array HPV Genotyping Test and next-generation sequencing (NGS). In general, the six most frequent HPV genotypes found by Linear Array were HPV6, 62, 61, 81, 16 and 51. On the other hand, employing NGS, a total of 36 HPV genotypes belonging to both alpha and beta genera were found. The genotypes with the greatest number of reads, according to the diagnostic group, were: HPV81, 45, 6, 51 and 61 in MSM without anal lesions (WAIN); HPV6, 61, 70, 62 and 66 in MSM with atypical lesions (AAL); HPV6, 11, 66, 81 and 61 in MSM with anal intraepithelial neoplasia grade I (AIN I); and HPV16, 81, 58, 61 and 52 with AIN III. Additionally, a great diversity of L1 variants was observed, especially in genotypes HPV16, 58, 61, 52, 45 and 59.


Subject(s)
Alphapapillomavirus/classification , Alphapapillomavirus/genetics , Genotype , HIV Infections/virology , Papillomavirus Infections/virology , Phylogeny , Adult , Alphapapillomavirus/isolation & purification , Anal Canal/virology , Coinfection , HIV/genetics , HIV/isolation & purification , High-Throughput Nucleotide Sequencing , Homosexuality, Male , Humans , Male , Mexico , Middle Aged , Molecular Typing , Oligonucleotide Array Sequence Analysis , Polymorphism, Genetic
9.
PLoS One ; 12(11): e0184540, 2017.
Article in English | MEDLINE | ID: mdl-29190725

ABSTRACT

BACKGROUND: No study has estimated the potential impact of Human Papillomavirus (HPV) vaccination in Puerto Rico, a population with considerable burden of HPV-related morbidities. We evaluated the health and economic impacts of implementing a vaccination strategy for females and males in Puerto Rico, with the quadrivalent HPV (HPV4) vaccine, under different vaccination scenarios. METHODS: We adapted a mathematical model which estimates the direct and indirect health benefits and costs of HPV4 vaccination in a dynamic population. The model compared three vaccination scenarios against screening only (no-vaccination) for three doses of HPV4 vaccine among individuals aged 11-15 years in Puerto Rico: 1) 34% for females and 13% for males (34%F/13%M), 2) 50% for females and 40% for males (50%F/40%M), and 3) 80% for female and 64% for male (80%F/64%M). Data specific to Puerto Rico was used. When not available, values from the United States were used. Input data consisted of demographic, behavioral, epidemiological, screening, and economic parameters. RESULTS: The model predicted decreases in: 1) HPV infection prevalence for females and males, 2) cervical intraepithelial neoplasia and cervical cancer incidence for females, 3) genital warts incidence for females and males, and 4) cervical cancer deaths among females, when various vaccination program scenarios were considered. In addition, when the vaccination percentage was increased in every scenario, the reduction was greater and began earlier. The analysis also evidenced an incremental cost effectiveness ratio (ICER) of $1,964 per quality-adjusted life year gained for the 80%F/64%M uptake scenario. CONCLUSIONS: HPV vaccine can prove its cost effectiveness and substantially reduce the burden and costs associated to various HPV-related conditions when targeted to the adequate population together with an organized HPV vaccination program.


Subject(s)
Models, Theoretical , Papillomavirus Vaccines/immunology , Adolescent , Alphapapillomavirus/classification , Alphapapillomavirus/immunology , Child , Female , Humans , Male , Papillomavirus Infections/prevention & control , Papillomavirus Infections/virology , Papillomavirus Vaccines/administration & dosage , Puerto Rico
10.
PLoS One ; 12(8): e0182854, 2017.
Article in English | MEDLINE | ID: mdl-28829791

ABSTRACT

BACKGROUND: Invasive cervical cancer (ICC) is the third most common malignant neoplasm affecting Brazilian women. Little is known about the impact of specific HPV genotypes in the prognosis of ICC. We hypothesized that HPV genotype would impact ICC clinical presentation and survival. METHODS: Women diagnosed with ICC at the Instituto do Câncer do Estado de São Paulo (ICESP) between May 2008 and June 2012 were included in the study and were followed until December 2015. HPV genotype was detected from formalin-fixed paraffin-embedded (FFPE) tumor tissue samples using Onclarity™ system (BD Viper™ LT automated system). RESULTS: 292 patients aged 50±14 years were analyzed. HPVDNA was detected in 84% of patients. The HPV genotypes studied were: HPV16 (64%), HPV18 (10%), HPV33-58 (7%), HPV45 (5%), HPV31 (4%) and other high-risk HPV genotypes (11%). HPV genotypes showed different distributions regarding histological type and clinical stage. Patients were followed for 35±21 months. The overall survival at 5 years after diagnosis of cervical cancer was 54%. Age, clinical staging, histological type and multiple HPV genotypes infection detected in the same tumor specimen were associated with poorer overall survival on multivariate Cox proportional hazard analysis (p<0.05). No specific HPV genotype affected survival. CONCLUSION: Multiple HPV genotype infection was associated with poorer ICC survival in our study, compared with single genotype infection. HPV genotyping from FFPE tumor tissue using an automated assay such as the Onclarity BD™ assay provides a simpler alternative for routine clinical use. IMPACT: This is the largest study employing an automated HPV genotyping assay using FFPE of ICC. Multiple HPV genotype infection adversely influenced survival.


Subject(s)
Alphapapillomavirus/classification , Genotype , Uterine Cervical Neoplasms/virology , Alphapapillomavirus/genetics , Female , Humans
11.
Med Microbiol Immunol ; 205(6): 585-594, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27539577

ABSTRACT

Cervical cancer is the fourth most common malignancy in women worldwide. In Chile, cervical cancer is the second leading cause of death among women of reproductive age, causing more than 600 deaths annually. This study was carried out to determine the burden and confirm the predominant human papillomavirus (HPV) genotypes among women presenting for cervical cancer screening in public health services in Chile. Women aged 18-64 years residing in the north and central areas covered by six primary care centers of Santiago, Chile, were invited to participate from March 2014 to August 2015. Cervical swabs were examined both HPV genotyping by PCR and Reverse Line Blot, and cervical cytology by Pap testing. A total of 1738 women were included in this study: 11.1 % were HPV positive, 9.7 % were high-risk types positive, 3.2 % were low-risk types positive, 1.4 % were Pap positive and 0.9 % were positive by both tests. The four most predominant genotypes were 16, 66, 51 and 59, with prevalence of 2.8, 1.4, 1.2 and 1.2 %, respectively. Multiple HPV infections were detected among 3.8 % participants. Age-specific prevalence of HPV showed a peak in HPV infection at younger ages (≤30 years), declining to a plateau in middle age. Among women with normal cytology, the 9.4 % were HPV positive, while 58.3 % of women with abnormal cytology were HPV positive. These findings show new epidemiological data confirming HPV 16 and 66 as the most predominant genotypes in Chile. These data are important for design successful strategies for prevention of cervical cancer in Chile.


Subject(s)
Alphapapillomavirus/classification , Alphapapillomavirus/genetics , Papillomavirus Infections/epidemiology , Papillomavirus Infections/virology , Uterine Cervical Neoplasms/epidemiology , Adolescent , Adult , Age Factors , Cervix Uteri/pathology , Cervix Uteri/virology , Chile/epidemiology , Early Detection of Cancer , Female , Genotype , Humans , Mass Screening , Middle Aged , Papillomavirus Infections/complications , Population Surveillance , Prevalence , Uterine Cervical Neoplasms/etiology , Uterine Cervical Neoplasms/pathology , Young Adult
12.
Genet Mol Res ; 14(4): 17252-61, 2015 Dec 17.
Article in English | MEDLINE | ID: mdl-26681219

ABSTRACT

In Uyghur women, mortality rates from cervical cancer are amongst the highest in the nation, and genetic susceptibility probably plays a role in the pathogenesis of the disease. We investigated the correlation between polymorphisms of the HLA-DQB1 allele and cervical cancer in Xinjiang Uyghur women. Cervix tissue samples from 80 cases of cervical cancer and 80 cases of cervicitis were genotyped using polymerase chain reaction-sequence-based typing (PCR-SBT) for HLA-DQB1. Two hundred and ninety-six alleles were identified among the 160 cases. One hundred and thirty-six alleles were heterozygous and 24 were homozygous. Using frequency calculations and statistical analysis, we found that HLA-DQB1*0325 (OR: 10.60, 1.341-83.81) and HLA-DQB1*0332 (OR: 12.59, 2.909-54.526) were more frequently identified in the cervical cancer group compared with the cervicitis group (P < 0.05). However, HLA-DQB1*0317 (OR: 0.49, 0.304-0.798) and HLA-DQB1*040302 (OR: 0.40, 0.243-0.658) were present less frequently in the cervical cancer group (P < 0.05). The frequency of the HLA-DQB1 genotype in Uyghur was different from that reported previously in other areas. HLA-DQB1*0325 and HLA-DQB1*0332 probably act as cervical cancer susceptibility genes in Uyghur women from Xinjiang. In contrast, HLA-DQB1*0317 and HLA-DQB1*040302 may be protective genes.


Subject(s)
Alleles , Ethnicity/genetics , HLA-DQ beta-Chains/genetics , Polymorphism, Genetic , Uterine Cervical Neoplasms/genetics , Adult , Alphapapillomavirus/classification , Alphapapillomavirus/genetics , Case-Control Studies , China/epidemiology , Exons , Female , Genetic Predisposition to Disease , Genotype , Humans , Middle Aged , Odds Ratio , Papillomavirus Infections/complications , Papillomavirus Infections/virology , Risk Factors , Sequence Analysis, DNA , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/etiology , Young Adult
13.
Clin Cancer Res ; 21(23): 5360-70, 2015 Dec 01.
Article in English | MEDLINE | ID: mdl-26080840

ABSTRACT

PURPOSE: Cervical cancer is one of the most common causes of cancer mortality for women living in poverty, causing more than 28,000 deaths annually in Latin America and 266,000 worldwide. To better understand the molecular basis of the disease, we ascertained blood and tumor samples from Guatemala and Venezuela and performed genomic characterization. EXPERIMENTAL DESIGN: We performed human papillomavirus (HPV) typing and identified somatically mutated genes using exome and ultra-deep targeted sequencing with confirmation in samples from Mexico. Copy number changes were also assessed in the exome sequence. RESULTS: Cervical cancer cases in Guatemala and Venezuela have an average age of diagnosis of 50 years and 5.6 children. Analysis of 675 tumors revealed activation of PIK3CA and other PI3K/AKT pathway genes in 31% of squamous carcinomas and 24% of adeno- and adenosquamous tumors, predominantly at two sites (E542K, E545K) in the helical domain of the PIK3CA gene. This distribution of PIK3CA mutations is distinct from most other cancer types and does not result in the in vitro phosphorylation of AKT. Somatic mutations were more frequent in squamous carcinomas diagnosed after the age of 50 years. Frequent gain of chromosome 3q was found, and low PIK3CA mutation fractions in many tumors suggest that PI3K mutation can be a late event in tumor progression. CONCLUSIONS: PI3K pathway mutation is important to cervical carcinogenesis in Latin America. Therapeutic agents that directly target PI3K could play a role in the therapy of this common malignancy.


Subject(s)
Genome, Human , Genomics , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/etiology , Adult , Aged , Alphapapillomavirus/classification , Alphapapillomavirus/genetics , Biomarkers, Tumor , Chromosome Mapping , Class I Phosphatidylinositol 3-Kinases , DNA Copy Number Variations , Exome , Female , Gene Expression , Guatemala/epidemiology , High-Throughput Nucleotide Sequencing , Humans , Mexico/epidemiology , Middle Aged , Mutation , Neoplasm Grading , Papillomavirus Infections/complications , Papillomavirus Infections/virology , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Phosphorylation , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Risk Factors , Signal Transduction , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology , Venezuela/epidemiology
14.
BMC Cancer ; 15: 100, 2015 Mar 05.
Article in English | MEDLINE | ID: mdl-25885207

ABSTRACT

BACKGROUND: Analysing human papillomavirus (HPV) viral load is important in determining the risk of developing cervical cancer (CC); most knowledge to date regarding HPV viral load and cervical lesions has been related to HPV-16. This study evaluated the association between the viral load of the six most prevalent high-risk viral types in Colombia and cervical intraepithelial neoplasia (CIN) frequency. METHODS: 114 women without CIN and 59 women having CIN confirmed by colposcopy, all of them positive by conventional PCR for HPV infection in the initial screening, were included in the study. Samples were tested for six high-risk HPV types to determine viral copy number by real-time PCR. Crude and adjusted odds ratios (ORa) were estimated for evaluating the association between each viral type's DNA load and the risk of cervical lesions occurring. RESULTS: The highest viral loads were identified for HPV-33 in CIN patients and for HPV-31 in patients without lesions (9.33 HPV copies, 2.95 interquartile range (IQR); 9.41 HPV copies, 2.58 IQR). Lesions were more frequent in HPV-16 patients having a low viral load (3.53 ORa, 1.16-10.74 95%CI) compared to those having high HPV-16 load (2.62 ORa, 1.08-6.35 95%CI). High viral load in HPV-31 patients was associated with lower CIN frequency (0.34 ORa, 0.15-0.78 95%CI). CONCLUSIONS: An association between HPV DNA load and CIN frequency was seen to be type-specific and may have depended on the duration of infection. This analysis has provided information for understanding the effect of HPV DNA load on cervical lesion development.


Subject(s)
Alphapapillomavirus/genetics , Cervix Uteri/pathology , Cervix Uteri/virology , DNA, Viral , Papillomavirus Infections/complications , Papillomavirus Infections/virology , Uterine Cervical Neoplasms/etiology , Uterine Cervical Neoplasms/pathology , Viral Load , Adult , Alphapapillomavirus/classification , Biopsy , Colombia/epidemiology , Female , Humans , Middle Aged , Odds Ratio , Risk Factors , Uterine Cervical Neoplasms/epidemiology , Young Adult , Uterine Cervical Dysplasia/epidemiology , Uterine Cervical Dysplasia/etiology , Uterine Cervical Dysplasia/pathology
15.
BMC Cancer ; 14: 451, 2014 Jun 18.
Article in English | MEDLINE | ID: mdl-24942545

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/mm(3) CD4-count (p = 0.004) and higher HIV-viral-load (p = 0.001). HPV-DNA detection, <200 cell/mm(3) 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.


Subject(s)
Coinfection/epidemiology , HIV Infections/epidemiology , Papillomavirus Infections/epidemiology , Adolescent , Adult , Aged , Alphapapillomavirus/classification , Alphapapillomavirus/genetics , CD4 Lymphocyte Count , Colombia/epidemiology , Cross-Sectional Studies , Female , HIV Infections/drug therapy , HIV Infections/immunology , HIV Infections/virology , HIV-1/genetics , Humans , Middle Aged , Papillomavirus Infections/complications , Prevalence , Risk Factors , Tumor Virus Infections/complications , Tumor Virus Infections/epidemiology , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/virology , Viral Load , Young Adult
16.
BMC Oral Health ; 14: 7, 2014 Jan 24.
Article in English | MEDLINE | ID: mdl-24460642

ABSTRACT

BACKGROUND: Human papillomavirus (HPV) is associated to the pathogenesis of various cancers, such as oropharyngeal squamous cell carcinoma, which has a high incidence in Puerto Rican men. Despite the burden of oral cancer in Puerto Rico, little is known about the epidemiology of oral HPV infection, particularly in high-risk men. Therefore, this study is aimed at determining the prevalence of oral HPV infection, the genotype distribution and correlates associated with oral HPV infection in men of at least 16 years of age attending a sexually transmitted infection (STI) clinic in Puerto Rico. METHODS: A cross-sectional study consisting of 205 men was conducted. Participants provided a 30-second oral rinse and gargle with mouthwash. Following DNA extraction, HPV genotyping was performed in all samples using Innogenetics Line Price Assay (INNO-LiPA). A questionnaire was administered, which included a demographic, behavioral and a clinical assessment. Descriptive statistics and bivariate analysis were used to characterize the study sample. Variables that achieved statistical significance in the bivariate analysis (p < 0.05) were assessed in multivariate logistic regression models. RESULTS: The mean age of the study sample was 38.5 ± 14.2 years. Oral HPV prevalence among men was 20.0% (95.0%CI = 14.8%-26.1%) and of HPV type 16 was 2.4% (95.0%CI = 0.8%-5.6%). Oral HPV prevalence significantly increased over increasing age categories (p-trend = 0.001). Multivariate analysis showed that oral HPV was independently associated with number of sexual partners (adjusted OR = 1.02; 95%CI = 1.01-1.03) and lifetime use of cigarettes (adjusted OR = 3.00; 95%CI = 0.98-9.16). CONCLUSIONS: Oral HPV among the sampled men in the STI clinic was high, regardless of the HIV status or sexual behavior. Interventions in STI clinics should include screening for HPV in the oral cavity for the early detection and reduction of long-term consequences of oral HPV infection, such as oropharyngeal cancer.


Subject(s)
Alphapapillomavirus/classification , Hispanic or Latino/statistics & numerical data , Mouth Diseases/virology , Papillomavirus Infections/epidemiology , Adolescent , Adult , Age Factors , Alphapapillomavirus/genetics , Cross-Sectional Studies , Genotype , HIV Infections/epidemiology , Human papillomavirus 16/genetics , Human papillomavirus 16/isolation & purification , Humans , Male , Middle Aged , Mouth Diseases/epidemiology , Prevalence , Puerto Rico/epidemiology , Risk Factors , Sexual Partners , Sexually Transmitted Diseases/epidemiology , Smoking/epidemiology , Young Adult
17.
PLoS One ; 9(1): e83209, 2014.
Article in English | MEDLINE | ID: mdl-24400071

ABSTRACT

PURPOSE: Recent studies in Puerto Rico have reported an increasing incidence of anal cancer in Puerto Rican men. The objective of this study was to determine the prevalence, genotype distribution and risk factors associated with anal HPV infection among men attending an STI clinic in Puerto Rico. METHODS: We conducted a cross-sectional study among 205 men 18 years and older. A comprehensive survey was administered that included a demographic and a behavioral assessment. Separate logistic regression models were performed to determine factors associated with any, high-risk (HR), and multiple anal HPV infection. RESULTS: The mean age of the study sample was 38.0±13.5 years. The most common HR types were 58, 51 and 31. Overall, HR anal HPV infection was found in 53.5% of the participants. Multiple HPV types in the anal canal were found in 47.6% of the sample. A third (29.8%) of participants reported being men who had sex with men (MSM). MSM had a significantly higher prevalence of any, HR and multiple HPV infection (p-value<0.05). Separate multivariate logistic regression analyses showed that being MSM was associated with any (OR = 4.5; [95%CI: 1.9-10.7]), HR (OR = 3.4; [95%CI: 1.1-10.3) and multiple anal HPV infection (OR = 3.6; [95%CI: 1.5-9.1). HIV was marginally associated with multiple anal HPV infection in multivariate analysis (OR = 3.3; 95%CI = 1.0-11.0). CONCLUSIONS: Anal HPV is common among sexually active men attending this STI clinic, with higher likelihood of anal HPV infection among MSM.


Subject(s)
Anal Canal/virology , Papillomavirus Infections/epidemiology , Sexually Transmitted Diseases/epidemiology , Adult , Alphapapillomavirus/classification , Alphapapillomavirus/genetics , Genotype , Humans , Male , Middle Aged , Papillomavirus Infections/transmission , Papillomavirus Infections/virology , Prevalence , Puerto Rico/epidemiology , Risk Factors , Sexual Behavior , Sexually Transmitted Diseases/transmission , Sexually Transmitted Diseases/virology , Young Adult
18.
J Med Virol ; 86(4): 647-52, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24375018

ABSTRACT

The aim of this work was to describe the prevalence of type-specific Human papillomavirus (HPV) infection in women attending organized cervical cancer screening program in Uruguay. Nine hundred sixty-five liquid cervical cell samples obtained after collection of cervical smears for cytology were assessed for HPV DNA using the Papillocheck system (Greiner BioOne). The overall prevalence of High-Risk (HR) HPV infections was 20.8% and increased from 16.5% in women with normal cytology to 93.3% in HSIL. Prevalence of HPV 16 and/or 18 was 6.3% and HPV 16 was the most prevalent genotype in normal cytology (3.6%). The five most prevalent genotypes were HPV 16, 31, 51, 56, and 39. The overall prevalence peaked below age 30. This study provides essential baseline information at national level on type-specific HPV prevalence in Uruguay before the introduction of HPV vaccination. It documents the current prevalence of each of the oncogenic genotypes in a population attending cervical cancer screening program, suggesting that at least 64.7% of high risk lesions are potentially preventable by available HPV vaccines, and possibly augmentable if cross-protection against non-vaccine HPV types 31, 33, and 45 is confirmed.


Subject(s)
Alphapapillomavirus/classification , Papillomavirus Infections/classification , Papillomavirus Infections/epidemiology , Adult , Age Factors , Aged , Cervix Uteri/virology , Cytological Techniques , DNA, Viral/genetics , Early Detection of Cancer , Female , Humans , Middle Aged , Papanicolaou Test , Uruguay/epidemiology , Uterine Cervical Neoplasms/prevention & control , Uterine Cervical Neoplasms/virology , Vaginal Smears , Uterine Cervical Dysplasia/virology
19.
Virology ; 448: 356-62, 2014 Jan 05.
Article in English | MEDLINE | ID: mdl-24314666

ABSTRACT

Human papillomavirus (HPV) 33, a member of the HPV16-related alpha-9 species group, is found in approximately 5% of cervical cancers worldwide. The current study aimed to characterize the genetic diversity of HPV33 and to explore the association of HPV33 variants with the risk for cervical cancer. Taking advantage of the International Agency for Research on Cancer biobank, we sequenced the entire E6 and E7 open reading frames of 213 HPV33-positive cervical samples from 30 countries. We identified 28 HPV33 variants that formed 5 phylogenetic groups: the previously identified A1, A2, and B (sub)lineages and the novel A3 and C (sub)lineages. The A1 sublineage was strongly over-represented in cervical cases compared to controls in both Africa and Europe. In conclusion, we provide a classification system for HPV33 variants based on the sequence of E6 and E7 and suggest that the association of HPV33 with cervical cancer may differ by variant (sub)lineage.


Subject(s)
Alphapapillomavirus/genetics , Alphapapillomavirus/isolation & purification , Genetic Variation , Papillomavirus Infections/virology , Uterine Cervical Neoplasms/virology , Africa , Alphapapillomavirus/chemistry , Alphapapillomavirus/classification , Amino Acid Sequence , Asia , Base Sequence , Europe , Female , Humans , Molecular Sequence Data , Oncogene Proteins, Viral/chemistry , Oncogene Proteins, Viral/genetics , Phylogeny , Sequence Alignment , South America
20.
Medicina (B Aires) ; 73(6): 585-96, 2013.
Article in Spanish | MEDLINE | ID: mdl-24356274

ABSTRACT

Cervical cancer (CC), which is strongly associated to high-risk human papillomavirus (hr-HPV) infection, continues being a significant health problem in Latin America. The use of conventional cytology to detect precancerous cervical lesions has had no major impact on reducing CC incidence and mortality rates, which are still high in the region. New screening tools to detect precancerous lesions became available, which provide great opportunities for CC prevention, as do highly efficacious HPV vaccines able to prevent nearly all lesions associated with HPV-16 and -18 when applied before viral exposure. Currently, hr-HPV testing represents an invaluable component of clinical guidelines for screening, management and treatment of CC and their precursor lesions. Many testing strategies have been developed that can detect a broad spectrum of hr-HPV types in a single assay; however, only a small subset of them has documented clinical performance for any of the standard HPV testing indications. HPV tests that have not been validated and lack proof of reliability, reproducibility and accuracy should not be used in clinical management. Once incorporated into the lab, it is essential to submit the whole procedure of HPV testing to continuous and rigorous quality assurance to avoid sub-optimal, potentially harmful practices. Recent progress and current status of these methods are discussed in this article.


Subject(s)
Alphapapillomavirus/isolation & purification , Oncogenic Viruses/isolation & purification , Papillomavirus Infections/diagnosis , Uterine Cervical Dysplasia/virology , Uterine Cervical Neoplasms/prevention & control , Alphapapillomavirus/classification , Alphapapillomavirus/genetics , Argentina/epidemiology , Early Detection of Cancer , Female , Humans , Incidence , Mass Screening/methods , Molecular Diagnostic Techniques/standards , Oncogenic Viruses/pathogenicity , Papillomavirus Infections/epidemiology , Papillomavirus Vaccines/therapeutic use , Sensitivity and Specificity , Uterine Cervical Neoplasms/virology , Uterine Cervical Dysplasia/prevention & control
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