Prevalence of anal high-risk human papillomavirus (HR-HPV) types in people living with HIV and a history of cancer.

This study aimed to describe the prevalence of high-risk human papillomavirus (HR-HPV) types in the anal canal in a cohort of people living with HIV (PLWHIV) with a history of malignancy. SETTING: Referral tertiary care hospital for adult patients with cancer. METHODS: We reviewed data of patients from the AIDS Cancer Clinic on antiretroviral therapy in chronic control who were consecutively referred for high-resolution anoscopy (HRA), where they underwent anal evaluation, collection of specimens for anal cytology and anal human papillomavirus (HPV) followed by HRA with directed biopsy if needed. RESULTS: A total of 155 patients were included; 149 (96.1%) were men, all of them men who have sex with men (MSM); the median age was 39 (IQR 32-47) years; 105 (67.7%) with Kaposi sarcoma, 40 (25.8%) with non-Hodgkin lymphoma and 10 (6.4%) with other neoplasms; only 7 (4.5%) had active cancer. The prevalence of HR-HPV infection was 89% (n=138) (95% CI 83-93) with at least one HR-HPV infection, and 62% (96) had coinfection with at least two types; the median HR-HPV types of coinfection were 3 (IQR 2-4). The number of patients infected with HPV 16 was 64 (41.3%, 95% CI 33.8-49.3), HPV 18 was 74 (47.7%, 95% CI 39.9-55.7) and with both 35 (22.6%). Some 59 patients (38%) had high-grade squamous intraepithelial lesions (HSIL) and 49 (31.6%) had low-grade squamous intraepithelial lesions (LSIL). The prevalence of HR-HPV and HSIL among patients aged ≤35 and >35 years was the same. CONCLUSIONS: In this cohort of PLWHIV with a history of malignancy we found a high prevalence of HR-HPV 16 and 18 and anal HSIL, even in persons aged ≤35 years. These data highlight the importance of anal cancer screening in PLWHIV and history of malignancy.

Prevalence of High-Risk Human Papillomavirus Genotypes among Young Women in Puerto Rico; a retrospective longitudinal study.

Background: Human Papillomavirus (HPV) is the most common sexually transmitted infection. High-risk HPV types are the main cause of cervical cancer. Annually, cervical cancer is among the top 10 cancers in Puerto Rican women, with 22% of these cases ending in death. The purpose of this study was to establish the prevalence of high-risk HPV genotypes in a large cohort of young women living in Puerto Rico. Methods: A retrospective longitudinal analysis was performed with a sample of 5,749 HPV results obtained from a clinical database of women ages 21 to 29 from 2014-2016. Results: Outcomes indicate that among those with a positive HPV result, about one-third (35.2%) had a high-risk HPV infection. Women between the ages of 21 to 23 showed the highest prevalence (40.6%) of high-risk HPV. Among genotypes HPV 16 and 18, genotype 16 was the most prevalent. Interestingly, 85.4% of results were positive for other high-risk HPV types other than 16 or 18. Of the 458 women who had at least two tests completed, 217 had an initial positive result for HPV and only 108 (49.7%) resolved the infection. Conclusions: This study confirms the high prevalence of several genotypes of high-risk HPV in young women in a large Puerto Rican sample.

Expression of HPV-16 E6 and E7 oncoproteins alters Chlamydia trachomatis developmental cycle and induces increased levels of immune regulatory molecules.

Introduction: Infection with Human Papillomavirus (HPV) is a recognized risk factor for Chlamydia trachomatis (CT) infection and vice versa. Coinfection of HPV and CT in women is a very common and usually asymptomatic finding that has been linked to increased risk of cervical cancer. It has been demonstrated that CT facilitates the entry of multiple high risk HPV genotypes, leading to damage of the mucosal barrier and interfering with immune responses and viral clearance, which ultimately favours viral persistence and malignant transformation. Although the facilitating effects elicited by CT infection on viral persistence have been reported, little is known about the consequences of HPV infection on CT development. Methods: Herein, we took advantage of a genetically modified human cervical cell line co-expressing HPV-16 major oncogenic proteins E6 and E7, as an experimental model allowing to investigate the possible effects that HPV infection would have on CT development. Results and discussion: Our results show that CT infection of HPV-16 E6E7 expressing cells induced an upregulation of the expression of E6E7 oncoproteins and host cell inhibitory molecules PD-L1, HVEM and CD160. Additionally, smaller chlamydial inclusions and reduced infectious progeny generation was observed in E6E7 cells. Ultrastructural analysis showed that expression of E6 and E7 did not alter total bacterial counts within inclusions but resulted in increased numbers of reticulate bodies (RB) and decreased production of infectious elementary bodies (EB). Our results indicate that during CT and HPV coinfection, E6 and E7 oncoproteins impair RB to EB transition and infectious progeny generation. On the other hand, higher expression of immune inhibitory molecules and HPV-16 E6E7 are cooperatively enhanced in CT-infected cells, which would favour both oncogenesis and immunosuppression. Our findings pose important implications for clinical management of patients with HPV and CT coinfection, suggesting that screening for the mutual infection could represent an opportunity to intervene and prevent severe reproductive health outcomes, such as cervical cancer and infertility.

Splicing Characterization and Isoform Switch Events in Human Keratinocytes Carrying Oncogenes from High-Risk HPV-16 and Low-Risk HPV-84.

Infection of epithelial cells with high-risk HPV (HR-HPV) types, followed by expression of virus oncogenic proteins (E5, E6, and E7), leads to genomic imbalance, suppression of tumor inhibitors, and induction of oncogenes. Low-risk HPV (LR-HPV) may slow the rate at which cervical cancer spreads to an invasive stage since co-infection with LR-HPV is linked to a decreased risk of future invasive cancer than infection with HR-HPV alone. We then propose that cancer-progressing changes may be distinguished through identifying the functional differences between LR-HPV and HR-HPV. Lentiviral strategies were followed to establish HaCaT cells with constitutive expression of HPV oncogenes. RNAseq experiments were designed to analyze the transcriptome modulations caused by each of the E5, E6, and E7 oncogenes of HPV-16 and HPV-84 in HaCaT cells. We identified enhanced RNA degradation, spliceosome, and RNA polymerase pathways related to mRNA processing. ATTS (alternative transcription termination site) was discovered to be more prevalent in cells with HPV-16E5 than HPV-84E5. In HPV-16E6-infected cells, ATTS gain was significantly higher than ATTS loss. Cells with HPV-16E7 had more isoforms with intron retention (IR) than those with HPV-84E7. We identified switches in ADAM10, CLSPN, and RNPS1 that led to greater expression of the coding isoforms in HR-HPV. The results of this work highlight differences between LR-HPV and HR-HPV in mRNA processing. Moreover, crucial cervical cancer-related switch events were detected.

HPV infection and 5mC/5hmC epigenetic markers in penile squamous cell carcinoma: new insights into prognostics.

BACKGROUND: Penile cancer is one of the most aggressive male tumors. Although it is preventable, the main etiologic causes are lifestyle behaviors and viral infection, such as human papillomavirus (HPV). Long-term epigenetic changes due to environmental factors change cell fate and promote carcinogenesis, being an important marker of prognosis. We evaluated epidemiological aspects of penile squamous cell carcinoma (SCC) and the prevalence of HPV infection using high-risk HPV (hrHPV) and p16INK4A expression of 224 participants. Global DNA methylation was evaluated through 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). RESULTS: The incidence of HPV was 53.2% for hrHPV and 22.32% for p16INK4a. hrHPV was not related to systemic or lymph node metastasis and locoregional recurrence, nor influenced the survival rate. P16INK4a seems to be a protective factor for death, which does not affect metastasis or tumor recurrence. Lymph node and systemic metastases and locoregional recurrence increase the risk of death. An increased 5mC mark was observed in penile SCC regardless of HPV infection. However, there is a reduction of the 5hmC mark for p16INK4a + (P = 0.024). Increased 5mC/5hmC ratio (> 1) was observed in 94.2% of penile SCC, irrespective of HPV infection. Despite the increase in 5mC, it seems not to affect the survival rate (HR = 1.06; 95% CI 0.33-3.38). CONCLUSIONS: P16INK4a seems to be a good prognosis marker for penile SCC and the increase in 5mC, an epigenetic mark of genomic stability, may support tumor progression leading to poor prognosis.

Cervicovaginal loads of Gardnerella spp. are increased in immunocompetent women with persistent high-risk human papillomavirus infection.

Introduction. Two high-oncogenic-risk human papilomavirus (hrHPV) genotypes - HPV16 and HPV18 - cause most of the cases of cervical cancer worldwide. Bacterial vaginosis is associated with increased hrHPV persistence, although the mechanism underlying this association remains unclear. Gardnerella spp. are detected in nearly all cases of bacterial vaginosis and are the major source of cervicovaginal sialidases. The NanH1 gene is present in virtually all Gardnerella sialidase-producing strains and has been proposed as a potential marker for persistent hrHPV infection.Hypothesis. Gardnerella spp. load and the NanH1 gene are associated with hrHPV persistence.Aim. To compare the cervicovaginal load of Gardnerella spp. and the frequency of the NanH1 gene between women with persistent HPV16 and/or HPV18 infection and those who cleared the infection after 11 months.Methodology. Among a population of 1638 HPV screened, we detected 104 with positive HPV16 and/or HPV18 results. Samples were obtained at two time points (baseline and at a median of 11 months at follow-up) and tested using the Linear Array HPV Genotyping kit (Roche Molecular Systems, Pleasanton, CA, USA). Based on their HPV16/HPV18 status at enrolment and follow-up, participants were assigned to 'persistence' or 'clearance' groups. We used cervicovaginal fluid samples obtained upon enrolment to determine the load of the 23 s rRNA gene of Gardnerella spp. and the presence of the NanH1 gene using real-time polymerase chain reaction (PCR). We compared Gardnerella spp. loads and NanH1 frequency between the groups by, respectively, Mann-Whitney and chi-squared tests, with a P-value <0.05 considered to be significant.Results. Of the 104 participants who were positive for HPV16/HPV18, 73 (70.2 %) persisted with at least 1 of the baseline genotypes at follow-up, while 31 (29.8 %) cleared the infection in this time frame. Participants in the persistence group had significantly higher loads of Gardnerella spp. [5.8E+02 (0-3.0E+05) copies µl-1] than those in the clearance group [9.9E+01 (0-7.7E+04) copies µl-1] (P=0.03). The baseline frequency of NanH1 was higher in the persistence' (n=46, 63.0 %) than in the clearance (n=14, 45.2 %) group, although this was not statistically significant (P=0.09).Conclusion. These findings reinforce the negative effect of vaginal microbiota for the clearance of hrHPV and indicate a possible association between sialidase-producing species with hrHPV persistence.

Prevalence and Distribution of Human Papillomavirus Genotypes (1997-2019) and Their Association With Cervical Cancer and Precursor Lesions in Women From Southern Mexico.

BACKGROUND: Cervical cancer (CC) is the fourth most common malignancy of the female genital tract. Human Papillomavirus (HPV) is the main cause of precancerous lesions and CC cases worldwide. OBJECTIVE: We assessed the prevalence and distribution of HPV types and their association with precancerous lesions and CC. METHODS: HPV genotypes were detected by 3 methods depending on the year of in which the sample was analyzed: MY09/11 RFLPs (1997 to 2010), GP5+/6+ primer systems (2005 to 2010) and INNO-LiPA HPV Genotyping Extra (2010 to 2019) in cervical samples (No-IL: 4445; LSIL: 2464; HSILs: 151 and CC: 253) from women from southern Mexico. RESULTS: The overall HPV prevalence was 54.17%, and hpv-16 was the most common genotype. In single infection, the high-risk HPV genotypes (group 1) were associated with squamous intraepitelial lesions (LSIL: HPV-39 (OR = 10.58, 95% CI 4.09-27.36, P < .001); HSIL: HPV-31 (OR = 14.76, 95% CI 6.56-33.20, P < .001); and CC: HPV-16 (OR = 25.01, 95% CI 18.83-33.21, P < .001). In multiple infections, the HPV genotypes (HPV-16 and HPV-18) were also associated with a high risk of lesions [LSIL: HPV-18 (OR = 3.45; 95% CI 1.36-8.91; P = .009); HSIL: HPV-18 (OR = 5.12; 95% CI 1.21-21.68; P = .026); and CC: HPV-16 (OR = 3.03; 95% CI 1.72-5.32; P < .001)] compared to single infection. In the analysis adjusted for age, giving birth, and cigarette smoking, a significant increase in the risk of LSIL, HSIL, and CC was maintained. CONCLUSIONS: This study provides current data on the prevalence and distribution of HPV genotypes in women from southern Mexico, which could serve as a valuable reference to guide nationwide CC screening programs and provide scientific evidence that could be useful for vaccine development efforts. Likewise, it was identified that infection with carcinogenic HPV genotypes is an independent risk factor for LSIL, HSIL, and CC.

Human papillomavirus co-infection and survival in oral and oropharyngeal squamous cell carcinoma: A study in 235 Brazilian patients.

OBJECTIVES: While unknown for oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC), some studies assessing cervical carcinoma have shown that human papillomavirus (HPV) co-infection can be associated with its prognosis. METHODS: Through in situ hybridization (HPV and Epstein-Barr virus [EBV] probes) and immunohistochemistry (p16INK4a, cyclin D1, p53, and Ki-67 antibodies), 126 OPSCC and 109 OSCC samples were assessed. RESULTS: All patients were EBV-negative. OPSCC (25%) showed a significant association with HPV compared to OSCC (11%). Almost all HPV-associated cases were p16INK4a-positive. Regarding OPSCC and OSCC, 23 and 7 cases were positive for high-risk HPV (HRHPV) only, 6 and 3 cases for low-risk HPV (LRHPV) only, and 3 and 2 cases for HRHPV/LRHPV, respectively. HPV-associated carcinomas showed a significantly higher proliferative index than HPV-unassociated carcinomas. Both carcinomas showed a similar overall survival rate, which was not affected by the HPV status. However, when comparing HPV-associated subgroups, patients with HRHPV/LRHPV-associated carcinomas showed worse survival. CONCLUSION: LRHPV-associated and HRHPV/LRHPV-associated cases can also be detected when assessing OSCC and OPSCC. Further studies, especially in populations with a high prevalence of HPV-associated OPSCC, are necessary to understand the clinicopathological behavior of these neoplasm subgroups.

Vaginal Microbiome Components as Correlates of Cervical Human Papillomavirus Infection.

BACKGROUND: Interplay between vaginal microbiome and human papillomavirus (HPV) remains unclear, partly due to heterogeneity of microbiota. METHODS: We used data from 546 women enrolled in a cross-sectional study in 5 Brazil. We genotyped vaginal samples for HPV and sequenced V3-V4 region of 16S rRNA gene for vaginal microbiome analysis. We used stepwise logistic regression to construct 2 linear scores to predict high-risk HPV (hrHPV) positivity: one based exclusively on presence of individual bacterial taxa (microbiome-based [MB] score) and the other exclusively on participants' sociodemographic, behavioral, and clinical (SBC) characteristics. MB score combined coefficients of 30 (of 116) species. SBC score retained 6 of 25 candidate variables. We constructed receiver operating characteristic curves for scores as hrHPV correlates and compared areas under the curve (AUC) and 95% confidence intervals (CI). RESULTS: Overall, prevalence of hrHPV was 15.8%, and 26.2% had a Lactobacillus-depleted microbiome. AUCs were 0.8022 (95% CI, .7517-.8527) for MB score and 0.7027 (95% CI, .6419-.7636) for SBC score (P = .0163). CONCLUSIONS: The proposed MB score is strongly correlated with hrHPV positivity-exceeding the predictive value of behavioral variables-suggesting its potential as an indicator of infection and possible value for clinical risk stratification.

Association of Righ-Risk Human Papillomavirus and Ureaplasma parvum Co-Infections with Increased Risk of Low-Grade Squamous Intraepithelial Cervical Lesions.

OBJECTIVE: The present report investigated the rates of coinfections between high-rik human papillomavirus (hrHPV) and the most important human mycoplasmas including Mycoplasma hominis, M. genitalium, Ureaplasma urealyticum and U. parvum in cervical samples of asymptomatic brazilian population. METHODS: Were included a total of 283 women aged 25-64 years screened by Papanicolaou smears for determining cervical abnormalities, single-target polymerase chain reaction (PCR) and real-time PCR (rt-PCR) for hrHPV and mycoplasmas, respectively. RESULTS: A total of 273 (94.5%) women were negative for intraepithelial lesions or malignancy cytology (NILM) and 10 (3.5%) presented abnormal cytology, all low-grade intraepithelial lesions (LSIL). The prevalence of hrHPV was 12.7% and 53.7% for mycoplasmas. U. parvum was the most frequently bacteria detected, followed by Mycoplasma hominis and U. urealyticum. M. genitalium was not detected. Women positive for U. parvum presented a 5-fold increased risk of LSIL (OR = 5.33; 95% CI = 1.09-26.04, P = 0.02) and co-infections between U. parvum and hrHPV increased the risk for LSIL (OR = 3.88; 95% CI = 1.75-8.58, P = 0.0003). However, these associations were not dependent on the concentration of the bacteria. CONCLUSION: Our results reinforced the hypothesis that some mycoplasmas may play a role as cofactors in HPV-mediated cervical carcinogenesis, at least in some populations.
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Prevalence and correlation of human papillomavirus genotypes with clinical factors in cervical samples from Mexican women.

IMPACT STATEMENT: We are submitting data regarding the prevalence and type distribution of the HPV infection and the risk factors associated with it, which may provide a valuable reference to reinforce screening strategies, and to maintain HPV genotype surveillance in Mexico. We discuss the overall prevalence of HPV infection as detected in normal cytological samples stratified by age, different types of infection, and oncogenic capacity. One of the most important findings was that common HPV genotypes detected in healthy women were the genotype numbers: 6, 31, 16, and 56, likewise, smoking and having a history of more than three sexual partners over their lifetime, represented the main risk factors in this study. Furthermore, we found a low frequency of cytological abnormalities and CIN 1-3 in women with HR-HPV.

The application value of PAX1 and ZNF582 gene methylation in high grade intraepithelial lesion and cervical cancer.

PURPOSE: To investigate the possibility of using the methylation level of PAX1/ZNF582 gene as molecular marker to differentiate the progression of cervical cancer. METHODS: From January 2016 to March 2018, 150 patients, who were admitted to Cervical Disease Diagnosis and Treatment Center of Xuzhu Maternity and Child Care Hospital, were enrolled in this study. Patients were classified into chronic cervicitis (for 19 cases), low-grade squamous intraepithelial lesion (LSIL) (18 cases), high-grade squamous intraepithelial lesion (HSIL) (37 cases) and squamous cell carcinoma (SCC) (31 cases). All patients underwent several tests including Thin-prep cytology test (TCT), HPV DNA detection and detection of methylation level of PAX1/ZNF582 genes. RESULTS: For diagnosis of HSIL, the area under curve (AUC) was 0.878 (95% CI 0.806 ~ 0.950); the threshold for PAX1 was 12.285, the sensitivity and specificity were 91.9% and 72.8%, respectively. The AUC of ZNF582 gene detection was 0.900 (95% CI 0.842 ~ 0.959), the threshold was 11.56, while the sensitivity and specificity were 97.3% and 76.7%, respectively. Among various tests we conducted, PAX gene detection methods showed the highest specificity (97.30%). PAX1/ZNF582 gene detection method demonstrated the highest accuracy. CONCLUSIONS: For patients with high-grade cervical lesion and cervical cancer, the methylation level of PAX1/ZNF582 gene could be applied as a noteworthy biomarker for diagnosis and for cervical cancer classification.

High-risk HPV clearance and CIN 3 treated with MAL-PDT: A case report.

High-grade cervical intraepithelial neoplasia (CIN) is the precursor to cervical cancer. HPV (human papillomavirus) infection is strongly related with this disease. The CIN treatment is generally excision of the transformation zone (ETZ). Photodynamic therapy (PDT) has also shown to be a promising treatment. We are reporting a case of a 33-years-old patient with high-grade CIN 3 treated with topical MAL (methyl aminolevulinate) PDT. Was applied 2.5 g of 20 % (w/w) MAL cream overnight and the cervix was illuminated twice, with three weeks apart, using a probe with LEDs simultaneously with a cylindrical laser fiber emitting both at 630 nm, with a fluency of 150 J/cm2. CIN 3 and the presence of high-risk HPV virus was eliminated 120 days after the second procedure. There was no recurrence at 6 months follow-up. This case report using MAL-PDT and a different light arrangement with LEDs and laser fiber associated both cured the patient with CIN 3 and eliminated low and high-risk HPV in just two PDT sessions.

Benefit of double-reading cytology smears as a triage strategy among high-risk human papillomavirus-positive women in Mexico.

BACKGROUND: The goal of this study was to determine whether the detection of histologically confirmed cases of cervical high-grade squamous intraepithelial lesions or worse (HSIL+) can be increased by having each liquid-based cytology (LBC) slide read by 2 cytotechnologists as part of routine screening. METHODS: Over 36,212 women aged 30 to 64 years participated in the Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage (FRIDA) Study in Mexico between 2013 and 2016. For each participant, 2 cervical samples were collected at the same clinic visit, one to test for high-risk human papillomavirus (hrHPV) and the other for LBC, which was used to triage those with a hrHPV positive result. LBC slides were evaluated by 7 cytotechnologists, with each slide read independently by 2 blinded cytotechnologists. All women with atypical cells of undetermined significance or a worse result were referred to colposcopy for further evaluation and diagnosis. Three pathologists evaluated the biopsy specimens to confirm the final HSIL+ diagnosis. The HSIL+ detection rates for the single versus double reading were estimated and compared. RESULTS: A total of 3,914 women with a positive hrHPV result were triaged with LBC. The first and second cytology readings resulted in 43 HSIL+ cases detected; the double-reading strategy detected 9 additional HSIL+ cases, resulting in a total of 52 HSIL+ cases. The HSIL+ detection rate increased from 10.99/1000 with a single reading to 13.29/1000 with the double-reading strategy (P = .004). CONCLUSION: A 20.9% increase in HSIL+ cases detected was achieved with a double reading of the LBC slides in this sample of hrHPV-positive women.

Prevalence of viral sexually transmitted infections and HPV high-risk genotypes in women in rural communities in the Department of La Paz, Bolivia.

BACKGROUND: Bolivia has the highest prevalence of cervical cancer in South America and the prevalence of viral sexually transmitted infections (STIs) among people in urban cities is increasing. Little is known about the prevalence of viral STIs in rural communities, which generally have limited access to health care. In order to study the prevalence of viral STIs in rural Bolivia, we recruited women from villages and towns in the Department of La Paz in Bolivia. METHODS: Three hundred ninety-four female participants were assessed for IgG-antibodies to herpes simplex virus type 2 (HSV-2), human immunodeficiency virus (HIV) and hepatitis B virus (HBV, anti-HBc), as well as for the presence of HBV surface antigen (HBsAg) in dried blood spots. The prevalence of 12 high-risk types of human papillomavirus (HPV) was assessed by qPCR in dried cervicovaginal cell spots from 376 of these women. χ2 test was used to compare variables between the populations and binary logistic regression was used to identify risk factors associated with the positivity of the tests. RESULTS: The seroprevalence of HSV-2 was 53% and of HBV 10.3%. HBAg was detected in 15.8% of women with anti-HBV antibodies indicating chronic infection. The frequency of high-risk HPV infection was 27%, with the most prevalent high-risk HPV types being HPV 56, 39 and 31 followed by HPV 16 and 18. Finally, none of the 394 women were seropositive for HIV, and about 64% of the studied population was positive for at least one of the viral infections. CONCLUSIONS: Women in Bolivian rural communities in La Paz show a high prevalence of HBV, HPV and, in particular, HSV-2. In contrast, none of the women were HIV positive, suggesting that the HIV prevalence in this population is low. The pattern of high-risk HPV types differed from many other countries with a predominance of HPV-types not included in the Gardasil vaccine which was officially introduced in Bolivia in April 2017.

Rural distribution of human papilloma virus in low- and middle-income countries.

Cervical cancer rates in low- and middle-income countries (LMICs) are higher than in developed countries and account for 80% of an estimated 500,000 new cases annually. Factors that contribute to this are that diagnostic and prevention strategies designed for developed countries suffer from the combination of low vaccination rates and limitations due to lack of consistent access to both healthcare and supplies. Here we: 1) improve upon our LMIC deployable HPV test and 2) determine both the high and low-risk HPV genotype prevalence in an isolated Honduran population. We found an unexpected HPV distribution with an abundance of HPV 52 and HPV 72 infections. In this context, molecular testing using a LMIC deployable approach for the detection of HPV can aid in both the triage of HPV positive cytology-based follow up and provide information regarding HPV genotype distribution in support of vaccination strategies.

Clinical, laboratory and epidemiological aspects of HPV infection in a low-income population from South Bahia, Brazil.

The aim of this study was to determine the prevalence and risk factors for human papillomavirus (HPV) infection in the Southern region of the State of Bahia, evaluating the performance of alternative complementary methods for cervical lesion detection. Cervical samples from women who attended healthcare units were collected and diagnosed by visual inspection, cervical cytology and nested polymerase chain reaction (PCR). Moreover, hemi-nested PCR was performed to detect different HPV genotypes. The prevalence of HPV infection was 47·7%, with genotype 16 detected in most cases. Infection was associated with dyspareunia and bleeding (P < 0·001, odds ratio (OR) 5·6, 95% confidence interval (CI) 2·815-11·14) and hormonal contraceptive use (P = 0·007, OR 2·33, 95% CI 1·25-4·34). There was a positive correlation between positive PCR and positive visual inspection, cervical cytology and symptoms reported. Furthermore, visual inspection was twice as specific, and had a greater positive predictive value than cytology. We showed a high prevalence of HPV infection in Southern Bahia, with HPV 16 being the most common type, and visual inspection being most effective at detecting HPV lesions, corroborating the suggestion that it can be applied in routine gynecologic examinations for low-income populations.

Prevalencia del virus del papiloma humano en mujeres con citología negativa / Prevalence of Human Papillomavirus Infection in Women with Negative Cytology

Introducción: la infección persistente por los subtipos oncogénicos del virus del papiloma humano es la causa principal del desarrollo del cáncer cérvico-uterino. Las mujeres que presentan citología normal pueden estar infectadas por subtipos de alto riesgo carcinogénico. Objetivo: brindar información actualizada existente en la literatura científica internacional acerca de la prevalencia de la infección por el virus del papiloma humano a nivel mundial y de la importancia de la detección temprana de estos virus en mujeres con citología negativa. Método: se realizó una revisión de los estudios desarrollados a nivel global y para esto se utilizaron las bases de datos PubMed, MedLine, BioMed Central y SciELO. Resultados: la prevalencia de la infección por los subtipos de alto riesgo del virus del papiloma humano en las mujeres con citología normal fue del 10 - 12 por ciento, con algunas diferencias entre países. El mayor pico de frecuencia de esta infección viral se localizó en jóvenes menores de 25 años y, en algunas regiones geográficas, se observó un segundo pico en mayores de 49 años. Los cinco subtipos oncogénicos más frecuentes de estos virus fueron 16, 18, 31, 52 y 58 con ciertas variaciones a nivel global. Conclusiones: el diagnóstico precoz de la infección por el virus del papiloma humano, especialmente los genotipos de alto riesgo, es un factor importante para una mejor prevención del cáncer cérvico-uterino(AU)

Introduction: Persistent infection with the oncogenic subtypes of human papillomavirus is the leading cause of cervical cancer. Women with normal cytology may be infected with subtypes of high carcinogenic risk. Objective: Provide updated information on the prevalence of human papillomavirus infection worldwide and the importance of their early detection in women with negative cytology. Methods: A review of the studies developed at a global level was carried out and PubMed, MedLine, BioMed Central, and SciELO databases were used. Results: The prevalence of infection with high - risk subtypes of human papillomavirus in women with normal cytology was 10 - 12 percent, with some differences between countries. The highest peak of frequency of this viral infection was located in young women under 25 years old and, in some geographic regions a second peak could be observed in those older than 49 years. The five most frequent oncogenic subtypes of these viruses were 16, 18, 31, 52 and 58 with certain variations globally. Conclusions: Early diagnosis of human papillomavirus infection, especially high-risk genotypes, is an important factor for better prevention of cervical-uterine cancer(AU)

Time trend analysis of cervical high-risk human papillomavirus (HPV) in HIV-infected women in an urban cohort from Rio de Janeiro, Brazil: the rise of non-16/18 HPV.

OBJECTIVES: HIV-infected women are at increased risk of human papillomavirus (HPV) infection. Time trends in annual prevalences of cervical high-risk human papillomavirus (HR-HPV) genotypes among a non-vaccinated, HIV-infected female cohort in urban Brazil were assessed for the period 2006-2012. METHODS: Cervical specimens were collected for HPV genotyping yearly between January 2006 and December 2012 in a cross-sectional analysis of participants aged ≥18 years enrolled in the Women's HIV Cohort at Fiocruz in Rio de Janeiro, Brazil. Age-adjusted generalized estimating equation models with an exchangeable matrix were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for annual HPV positivity (reference year: 2006). RESULTS: Among the 590 participants, the median age across all study years ranged from 35.5 to 40.0 years. The prevalence of any HR-HPV was ≥53% every year; prevalences of HR-HPV 16, 58, 59, and 68 were ≥24% in at least 1 year. The odds of HPV 16 and 68 decreased in 2012. HPV 58 prevalence followed a U-shape, beginning and ending at >20%. HPV 59 prevalence followed a linear trend, with increased odds in 2012 (OR 16.0, 95% CI 3.8-67.3; Bonferroni-adjusted p-value <0.01). CONCLUSIONS: The prevalences of HR-HPV 58, 59, and 68 were high in this cohort. Given current HR-HPV vaccine coverage and availability, further investigations are needed to optimize vaccine recommendations for this population.

[General aspects of structure, classification and replication of human papillomavirus]. / Aspectos generales de la estructura, la clasificación y la replicación del virus del papiloma humano.

Human papillomavirus (HPV) refers to a group of viruses which belongs to a larger group, commonly referred to as papillomaviruses. These viruses are taxonomically located in the Papillomaviridae family. Papillomaviruses are small, non-enveloped with a genome of double-stranded DNA and they have affinity for epithelial tissue. Many of them are associated with human infection; they induce benign lesions of the skin (warts) and mucous membranes (condylomas), but they are also associated with some epithelial malignancies, such as cervical cancer and other tumors of the urogenital tract. Papillomaviridae contains 16 genera, which are named with a Greek letter prefix and the termination papillomavirus, e.g., Alphapapillomavirus, Betapapillomavirus, etcetera. From the clinical point of view, human papillomaviruses infecting the genital tract (which are located in the genus Alphapapilomavirus) have been divided into two groups: those of low risk, associated with benign genital warts, and those of high risk, with oncogenic potential, which are the etiological agents of cervical cancer. In this paper we review some relevant aspects of the structure, replication cycle and classification of human papillomaviruses.

Virus del papiloma humano (VPH) hace referencia a un grupo de virus que se encuentra a su vez en un grupo mayor denominado comúnmente papilomavirus, y que se ubica taxonómicamente en la familia Papillomaviridae. Los papilomavirus son virus pequeños, no envueltos con genoma de ADN de doble cadena y que tienen afinidad por el tejido epitelial. Muchos de ellos están asociados con infección en humanos; producen lesiones en piel (verrugas) y en mucosas (condilomas), pero también están asociados con algunos procesos malignos en epitelio, como cáncer cervicouterino y otros tumores del tracto anogenital. La familia Papillomaviridae contiene 16 géneros, los cuales son nombrados con una letra griega como prefijo y con la terminación papillomavirus; por ejemplo: Alphapapillomavirus, Betapapillomavirus, etcétera. Desde el punto de vista clínico, los papilomavirus humanos que infectan la mucosa del tracto genital (los cuales están ubicados en el género Alphapapilomavirus) han sido divididos en dos grupos: los de bajo riesgo, que se asocian principalmente con verrugas genitales benignas, y los de alto riesgo, que presentan un alto potencial oncogénico y son los agentes etiológicos del cáncer cervicouterino. En este artículo revisamos algunos aspectos sobresalientes de la estructura, el ciclo replicativo y la clasificación de los virus de papiloma humano.