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1.
Eur J Cancer Prev ; 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32109928

RESUMO

Clinical guidelines recommend particular approaches, including 'screen-and-treat' strategy for Helicobacter pylori, to prevent gastric cancer. However, little of this is implemented in clinical practice. The aim of the study was to identify barriers to implementation of international guidelines. A web-based questionnaire distributed globally to specialists in the field. Altogether 886 responses from 75 countries were received. Of the responders, 570 (64%) were men of mean age 47 years. There were 606 gastroenterologists and 65 epidemiologists among the responders. Altogether, 79.8% of the responders disagreed that the burden of gastric cancer is a diminishing problem. 'Screen-and-treat' strategy for H. pylori in the responder's country was considered appropriate by 44.4%, inappropriate by 24.3%, with 31.3% being uncertain. Population-based screening for gastric cancer was considered appropriate in the respective home-country by 62.2%, in other areas - but not the home country - by 27.6%, and inappropriate by 10.2%. As a screening tool, upper endoscopy was acceptable by 35.6%, upper X-ray series by 55.3%, pepsinogens by 26.2% and breath-tests by 23.4%; accuracy, cost-effectiveness and feasibility among the tests varied widely. The attitude towards H. pylori vaccination was that 4.6% of the responders were eager to start vaccination immediately, 55.9% were supporting vaccination but considered that more data are required 12% were negative, and 27.6% did not have an opinion. In general, the attitude of the specialists was in line with guidelines, but was not always translated into clinical practice, particularly in the case of 'screen-and-treat' strategy.

2.
J Natl Cancer Inst ; 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32091594

RESUMO

BACKGROUND: Investigate the durability of vaccine efficacy (VE) against HPV16/18 infections and antibody response among non-randomized women who received a single-dose of the bivalent HPV vaccine compared to women who received multiple doses and unvaccinated women. METHODS: HPV infections were compared between HPV16/18 vaccinated women aged 18 to 25 years who received one (N = 112), two (N = 62), or three (N = 1365) doses, and age- and geography-matched unvaccinated women (N = 1783) in the long-term followup of the Costa Rica HPV Vaccine Trial. Cervical HPV infections were measured at two study visits, approximately 9- and 11-years after initial HPV vaccination, using NCI next-generation sequencing TypeSeq1 assay. VE and 95% confidence intervals (CI) were estimated. HPV16/18-antibody levels were measured on all one- and two-dose women, and a subset of three-dose women, using a virus-like particle-based ELISA (n = 448). RESULTS: Median follow-up for the HPV-vaccinated group was 11.3 years (interquartile range [IQR]: 10.9-11.7 years) and did not vary by dose group. VE against prevalent HPV16/18 infection was 80.2% (95%CI 70.7-87.0%) among three-dose, 83.8% (95%CI 19.5-99.2%) among two-dose, and 82.1% (95%CI 40.2-97.0%) among single-dose women. HPV16/18 antibody levels did not qualitatively decline between years four and 11, regardless of the number of doses given, although one-dose titers continue to be statistically significantly lower compared to two- and three-doses. CONCLUSION: More than a decade after HPV vaccination, single-dose VE against HPV16/18 infection remained high and HPV16/18 antibodies remained stable. A single dose of bivalent HPV vaccine may induce sufficiently durable protection that obviates the need for more doses.

3.
J Natl Cancer Inst ; 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32091596

RESUMO

BACKGROUND: The Costa Rica HPV Vaccine Trial (CVT) has documented cross-protection of the bivalent HPV vaccine against HPV31/33/45 up to seven years after vaccination, even with one dose of the vaccine. However, the durability of such protection remains unknown. Here, we evaluate different schedules of the vaccine's efficacy against HPV31/33/45 out to 11 years post-vaccination, expanding to other non-targeted HPV types. METHODS: We compared the rates of HPV infection in vaccinated women to the rates in a comparable cohort of unvaccinated women. We estimated the average vaccine efficacy (VEavg) against incident infections and tested for a change in VE over time. RESULTS: Among 3-dose women, we observed statistically significant cross-protection against HPV31/33/45 (VEavg=64.4%, 95%CI: 57.7% to 70.0%). Additionally, we observed borderline, statistically significant cross-protection against HPV35 (VEavg=23.2%, 95%CI: 0.3% to 40.8%) and HPV58 (VEavg=21.2%, 95%CI: 4.2% to 35.3%). There was no decrease in VE over time (two-sided p-for-trend>0.05 for HPV31, 33, 35, 45, 58). As a benchmark, VEavg against HPV16/18 was 82.0% (95%CI: 77.3% to 85.7%). Among 1-dose women, we observed comparable efficacy against HPV31/33/45 (VEavg=54.4%, 95%CI: 21.0% to 73.7%). Acquisition of non-protected HPV types was similar between vaccinated and unvaccinated women, indicating that the difference in HPV infection rates was not attributable to differential genital HPV exposure. CONCLUSION: Substantial cross-protection afforded by the bivalent vaccine against HPV31/33/45 and, to a lesser extent, HPV35 and HPV58, was sustained and remained stable after 11 years post-vaccination, reinforcing the notion that the vaccine is an effective option for protection against HPV-associated cancers.

4.
Asian Pac J Cancer Prev ; 20(12): 3825-3829, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31870128

RESUMO

BACKGROUND: Atrophic gastritis is considered precursor condition for gastric cancer. There is so far limited evidence on the performance of pepsinogens for atrophy detection in Central Asia. The aim of our study was to detect the prevalence of atrophic gastritis in the asymptomatic adult population in Kazakhstan as well as address the accuracy of pepsinogen testing in atrophy detection. METHODS: Healthy individuals aged 40-64 were included. Upper endoscopy and pepsinogens (PG) evaluation were performed. PG were analysed in plasma by latex agglutination. Cut off values were used to define decreased PG values (PGR ≤ 3 and PG I ≤ 70 ng/mL); severely decreased PG values (PGR ≤ 2 and PG I ≤ 30 ng/mL). Biopsies were analyzed and obtained according to the updated Sydney System. PG test sensitivity, specificity and overall accuracy were assessed using the histological diagnosis as the "gold standard". RESULTS: Altogether 157 individuals - female 40,1% and male 59,9% were included. Histologically, moderate to severe corpus atrophy, was present only in 1,3% cases. From all study subjects, 26,8% had decreased plasma PG values with cut-off values PGR ≤ 3 and PG I ≤ 70 ng/mL. The sensitivity of the PG test with this cut-off values was 50,0%, specificity 73,5%, overall accuracy 73,2% for detection of moderate to severe atrophy in the corpus. The sensitivity of PG test with cut-off values PGR ≤ 2 and PG I ≤30 ng/mL was 50,0%, specificity 90,9% and overall accuracy 90,4%. CONCLUSIONS: The prevalence of gastric mucosal atrophy was low in the Kazakh population. Serological PG test screening nevertheless can play an important role in the diagnosis of gastric precancerous lesions. However, the diagnostic accuracy of the PG test is mainly dependent on the cut-off values for positive results.

5.
Rev. méd. Urug ; 35(4): 267-280, dic. 2019. tab, fig
Artigo em Espanhol | LILACS | ID: biblio-1026117

RESUMO

Introduccción: en Uruguay, el cáncer de cuello uterino ocupó el tercer lugar con una incidencia promedio de 312 nuevos casos por año; fallecieron 134 mujeres promedio por año en el período 2010 - 2014. Objetivo: el objetivo de este trabajo fue analizar los primeros resultados de una experiencia piloto con la aplicación del test de HPV captura híbrida HC2 (QiagenR) como test de tamizaje primario del cáncer de cuello uterino en una zona del departamento de Canelones. Método: se estudiaron 1.010 mujeres asintomáticas entre 30 y 64 años que concurrieron a realizarse el test de PAP a dos unidades de toma de muestras del Programa de prevención del cáncer de cuello uterino. Se realizó la extracción conjunta de la muestra para PAP, que fue derivada a uno de los laboratorios de citología de la Red de Atención Primaria de Salud y la muestra de HPV que fue procesada con la técnica de captura híbrida en el laboratorio de biología molecular del Centro Hospitalario Pereira Rossell. Las usuarias con resultados HPV + y PAP anormales (ASC-US+) fueron derivadas a colposcopia, con biopsia y posterior tratamiento cuando correspondió. Resultados: el test de HPV fue positivo en 126/1.010 mujeres (12,5%) y el PAP anormal en 167/1.010 (16,5%). El test de HPV fue positivo en todos los casos CIN2+ 13/13 (100%) mientras que el PAP fue anormal (ASCUS+) en 7/13 (54%) para CIN2+ por biopsia. Conclusión: el test de HPV resultó más eficaz y eficiente que el PAP para la detección de lesiones precancerosas de cuello uterino.


Introduction: in Uruguay, cervical cancer occupied the third place with an average incidence of 312 new cases per year. 134 women died in the 2010 -2014 period. Objective: the study aims to analyse the first results in a pilot experience with the application of Hybrid Capture® 2 High-Risk HPV DNA Test™ (hc2) (QiagenR) as the primary screening test for cervical cancer, in the Department of Canelones. Method: 1.010 asymptomatic women whose ages ranged between 30 and 64 years old were studied when they requested a pap smear at two units of sample taking within the Cervical Cancer Prevention Program. Samples were taken along with the pap smear, and sent to one of the cytology labs in the primary health care network, the HPV sample being processed with the hybrid capture technique in the molecular biology laboratory of the Pereira Rossell Hospital Center. Users with abnormal HPV+ and abnormal pap smear results (ASCUS+) were referred to colposcopy, with subsequent biopsy and treatment if required. Results: HPV test was positive in 126/1010 women (12.5%) and PAP was abnormal in 167/1010 cases (16.5%). HPV test was positive in all cases CIN2+ 13/13 (100%) whereas PAP was abnormal (ASCUS+) in 7/13 54%) for CIN2+ in biopsy. Conclusion: HPV test was more effective and efficient than pap smear to detect pre-cancer lesions in the cervix.


Introdução: no Uruguai, no período 2010 - 2014, o câncer de colo do útero foi a terceira causa com uma incidência média de 312 novos casos por ano e uma média de 134 mortes por ano. Objetivo: o objetivo deste trabalho foi analisar os primeiros resultados de uma experiência piloto com a utilização do exame de HPV Captura Híbrida HC2 (QiagenR) na tamizagem primária do câncer de colo do útero em una zona do departamento de Canelones. Método: foram estudadas 1010 mulheres assintomáticas, com idades entre 30 e 64 anos que foram a duas unidades do Programa de Prevenção do Câncer do Colo do Útero para a coleta de amostra para exame de Papanicolau (PAP). Realizou-se uma única extração para duas amostras: uma para PAP, que foi encaminhada a um laboratório de citologia da rede de atenção primária de saúde e outra para o exame de HPV que foi processada com a técnica de captura híbrida no laboratório de biologia molecular do Centro Hospitalario Pereira Rossell. As usuárias com resultados HPV + e PAP anormais (ASCUS+) foram encaminhadas para realização de colposcopia, com biopsia e tratamento quando fosse necessário. Resultados: o exame de HPV foi positivo em 126/1010 mulheres (12.5%) e o PAP foi anormal em 167/1010 (16.5%). O exame de HPV foi positivo em todos los casos CIN2+ 13/13 (100%) e o PAP foi anormal (ASCUS+) em 7/13 (54%) para CIN2+ por biopsia. Conclusão: o exame de HPV foi mais eficaz e eficiente que o PAP para detecção de lesões pré-cancerosas de colo do útero.


Assuntos
Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Programas de Rastreamento/métodos , Infecções por Papillomavirus/diagnóstico , Teste de Papanicolaou
6.
J Natl Cancer Inst ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31697384

RESUMO

BACKGROUND: The AS04-adjuvanted HPV-16/18 (AS04-HPV-16/18) vaccine provides excellent protection against targeted HPV types and a variable degree of cross-protection against others, including types 6/11/31/33/45. High efficacy against any cervical intraepithelial neoplasia grade 3 or greater (CIN3+; >90%) suggests lower levels of protection may exist for a wide-range of oncogenic HPV types, which is difficult to quantify in individual trials. Pooling individual-level data from two randomized controlled trials (RCTs), we aimed to evaluate AS04-HPV-16/18 vaccine efficacy against incident HPV infections and cervical abnormalities. METHODS: Data were available from the Costa Rica Vaccine Trial (CVT; NCT00128661) and PATRICIA trial (NCT00122681) - two large-scale, double-blind RCTs of the AS04-HPV-16/18 vaccine. Primary analyses focused on disease-free women with no detectable cervicovaginal HPV at baseline. RESULTS: 12,550 women were included in our primary analyses (HPV arm=6,271; control arm=6,279). Incidence of six month persistent oncogenic/non-oncogenic infections, excluding known/accepted protected types 6/11/16/18/31/33/45 (focusing on 34/35/39/40/42/43/44/51/52/53/54/56/58/59/66/68/73/70/74), was statistically significantly lower in the HPV arm than in the control arm (efficacy=9.9%, 95% Confidence Interval [CI] 1.7%-17.4%). Statistically significant efficacy (p < 0.05) was observed for individual oncogenic types 16/18/31/33/45/52 and non-oncogenic types 6/11/53/74. Efficacy against cervical abnormalities (all types) increased with severity, ranging from 27.7% (95% CI 21.7%-33.3%) to 58.7% (95% CI 34.1%-74.7%) for cytologic outcomes (low-grade squamous intraepithelial neoplasia lesion or greater, and high-grade squamous intraepithelial neoplasia lesion or greater, respectively) and 66.0% (95% CI 54.4%-74.9%) to 87.8% (95% CI 71.1%-95.7%) for histologic outcomes (CIN2+ and CIN3+, respectively). Comparing CVT and PATRICIA results, there was no evidence of heterogeneity, except for type 51 (efficacy=-28.6% and 20.7%, respectively; two-sided p = 0.03). CONCLUSIONS: The AS04-HPV-16/18 vaccine provides some additional cross-protection beyond established protected types, which partially explains the high efficacy against CIN3+.

7.
PLoS One ; 14(11): e0224667, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31675357

RESUMO

BACKGROUND: Reaching an acceptable participation rate in screening programs is challenging. With the objective of supporting the Belarus government to implement mammography screening as a single intervention, we analyse the main determinants of breast cancer screening participation. METHODS: We developed a discrete choice experiment using a mixed research approach, comprising a literature review, in-depth interviews with key informants (n = 23), "think aloud" pilots (n = 10) and quantitative measurement of stated preferences for a representative sample of Belarus women (n = 428, 89% response rate). The choice data were analysed using a latent class logit model with four classes selected based on statistical (consistent Akaike information criterion) and interpretational considerations. RESULTS: Women in the sample were representative of all six geographic regions, mainly urban (81%), and high-education (31%) characteristics. Preferences of women in all four classes were primarily influenced by the perceived reliability of the test (sensitivity and screening method) and costs. Travel and waiting time were important components in the decision for 34% of women. Most women in Belarus preferred mammography screening to the existing clinical breast examination (90%). However, if the national screening program is restricted in capacity, this proportion of women will drop to 55%. Women in all four classes preferred combined screening (mammography with clinical breast examination) to single mammography. While this preference was stronger if lower test sensitivity was assumed, 28% of women consistently gave more importance to combined screening than to test sensitivity. CONCLUSION: Women in Belarus were favourable to mammography screening. Population should be informed that there are no benefits of combined screening compared to single mammography. The results of this study are directly relevant to policy makers and help them targeting the screening population.

8.
Cancer Epidemiol ; 63: 101615, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31586822

RESUMO

BACKGROUND: Tobacco use is a well-established risk factor for head and neck cancer (HNC). However, less is known about the potential impact of exposure to tobacco at an early age on HNC risk. METHODS: We analyzed individual-level data on ever tobacco smokers from 27 case-control studies (17,146 HNC cases and 17,449 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random-effects logistic regression models. RESULTS: Without adjusting for tobacco packyears, we observed that younger age at starting tobacco use was associated with an increased HNC risk for ever smokers (OR<10 years vs. ≥30 years: 1.64, 95% CI: 1.35, 1.97). However, the observed association between age at starting tobacco use and HNC risk became null after adjusting for tobacco packyears (OR<10 years vs. ≥30 years: 0.97, 95% CI: 0.80, 1.19). In the stratified analyses on HNC subsites by tobacco packyears or years since quitting, no difference in the association between age at start and HNC risk was observed. CONCLUSIONS: Results from this pooled analysis suggest that increased HNC risks observed with earlier age at starting tobacco smoking are largely due to longer duration and higher cumulative tobacco exposures.

9.
J Infect Dis ; 220(10): 1609-1619, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31536132

RESUMO

BACKGROUND: Human papillomaviruses (HPV) cause over 500 000 cervical cancers each year, most of which occur in low-resource settings. Human papillomavirus genotyping is important to study natural history and vaccine efficacy. We evaluated TypeSeq, a novel, next-generation, sequencing-based assay that detects 51 HPV genotypes, in 2 large international epidemiologic studies. METHODS: TypeSeq was evaluated in 2804 cervical specimens from the Study to Understand Cervical Cancer Endpoints and Early Determinants (SUCCEED) and in 2357 specimens from the Costa Rica Vaccine Trial (CVT). Positive agreement and risks of precancer for individual genotypes were calculated for TypeSeq in comparison to Linear Array (SUCCEED). In CVT, positive agreement and vaccine efficacy were calculated for TypeSeq and SPF10-LiPA. RESULTS: We observed high overall and positive agreement for most genotypes between TypeSeq and Linear Array in SUCCEED and SPF10-LiPA in CVT. There was no significant difference in risk of precancer between TypeSeq and Linear Array in SUCCEED or in estimates of vaccine efficacy between TypeSeq and SPF10-LiPA in CVT. CONCLUSIONS: The agreement of TypeSeq with Linear Array and SPF10-LiPA, 2 well established standards for HPV genotyping, demonstrates its high accuracy. TypeSeq provides high-throughput, affordable HPV genotyping for world-wide studies of cervical precancer risk and of HPV vaccine efficacy.

11.
PLoS One ; 14(6): e0218016, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31246959

RESUMO

BACKGROUND: Cervical cancer (CC) is one of the leading causes of cancer mortality among women from Paraguay, with high incidence and mortality rates (31.2 and 16 per 100 000 women, respectively). Although the risk factors associated with high-risk human papillomavirus (hrHPV) infection and preneoplastic cervical lesions are widely studied, population-based characteristics of particular settings may influence the feasibility of HPV-based CC screening implementation. This study aimed to explore factors associated with hrHPV infection and high-grade cervical neoplasia in hrHPV-positive (hrHPV+) women from Paraguay. METHODS: A total of 5677 women aged 30-64 years from the Central Department of Paraguay were screened with HPV test (Hybrid Capture 2) and Pap smear. Sociodemographic and risk factor interviews were conducted. hrHPV+ women were referred to colposcopy and women with an abnormal colposcopy had a biopsy taken. The outcomes recorded were the hrHPV status and the presence of high-grade cervical intraepithelial neoplasia or worse (CIN2+) among hrHPV+ women. Associations were investigated using multivariate logistic regressions. RESULTS: hrHPV prevalence was 13.8% (95%CI 13.0-14.8). This value decreased with the age of women (p-trend<0.001) and increased with the lifetime number of sexual partners (p-trend<0.001) and number of previous female partners of their current male partner if women had had one lifetime sexual partner (p-trend<0.001), increasing from 3.06 (95%CI 0.073-20.9) if partners had had one previous female partner to 9.19 (95%CI 2.36-61.1) if they had had eight or more. In hrHPV+ women, CIN2+ prevalence was 10.7% (95%CI 8.58-13.2) and increased with time since the last Pap smear (p-trend<0.001) and with the increasing number of pregnancies (p-trend = 0.05). CONCLUSION: In these settings, the sexual behavior of women and their male partners is associated with hrHPV infection. In hrHPV+ women, underscreening practices and multiple pregnancies are associated with CIN2+. This knowledge can contribute to public health policies for CC prevention and control in Paraguay.


Assuntos
Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Adulto , Idoso , Feminino , Geografia , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Razão de Chances , Infecções por Papillomavirus/patologia , Paraguai/epidemiologia , Prevalência , Fatores de Risco , Neoplasias do Colo do Útero/patologia
12.
Oral Oncol ; 94: 47-57, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31178212

RESUMO

OBJECTIVES: This study aimed at re-evaluating the strength and shape of the dose-response relationship between the combined (or joint) effect of intensity and duration of cigarette smoking and the risk of head and neck cancer (HNC). We explored this issue considering bivariate spline models, where smoking intensity and duration were treated as interacting continuous exposures. MATERIALS AND METHODS: We pooled individual-level data from 33 case-control studies (18,260 HNC cases and 29,844 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. In bivariate regression spline models, exposures to cigarette smoking intensity and duration (compared with never smokers) were modeled as a linear piecewise function within a logistic regression also including potential confounders. We jointly estimated the optimal knot locations and regression parameters within the Bayesian framework. RESULTS: For oral-cavity/pharyngeal (OCP) cancers, an odds ratio (OR) >5 was reached after 30 years in current smokers of ∼20 or more cigarettes/day. Patterns of OCP cancer risk in current smokers differed across strata of alcohol intensity. For laryngeal cancer, ORs >20 were found for current smokers of ≥20 cigarettes/day for ≥30  years. In former smokers who quit ≥10  years ago, the ORs were approximately halved for OCP cancers, and ∼1/3 for laryngeal cancer, as compared to the same levels of intensity and duration in current smokers. CONCLUSION: Referring to bivariate spline models, this study better quantified the joint effect of intensity and duration of cigarette smoking on HNC risk, further stressing the need of smoking cessation policies.

13.
Lancet Glob Health ; 7(6): e772-e783, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31097279

RESUMO

BACKGROUND: Human papillomavirus (HPV) testing for cervical cancer prevention was introduced in Argentina through the Jujuy Demonstration Project (2011-14). The programme tested women aged 30 years and older attending the public health system with clinician-collected HPV tests. HPV self-collection was introduced as a programmatic strategy in 2014. We aimed to evaluate the effectiveness of programmatic HPV testing to detect cervical intraepithelial neoplasia (CIN) of grade 2 or worse (CIN2+) in comparison with cytology-based screening. METHODS: We did a population-based, before-and-after retrospective cohort study using data from the National Cervical Cancer Prevention Program for the Jujuy province in northwest Argentina. We obtained data for the cytology-based screening period from Jan 1, 2010, until Dec 31, 2011, and for the HPV-based screening period from Jan 1, 2012, until Dec 31, 2014. The primary outcome was detection of histologically diagnosed CIN2+ among women aged 30 years and older. To assess the outcomes in all individuals included in the study, we used multivariable logistic regression and propensity score matching. The reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework was used for the before-and-after analysis of programmatic dimensions. FINDINGS: Of the 29 631 women who underwent cytology-based screening in 2010-11, CIN2+ was detected in 236 (0·8%) individuals. Of the 49 565 women HPV tested in 2012-14 (clinician-collected tests, n=44 700; self-collection tests, n=4865), 693 (1·4%; 658 clinician-collected tests; 35 self-collection tests) were found to have CIN2+ after the first round of screening. Compared with cytology-based screening, the odds ratio of being diagnosed with a CIN2+ lesion was 2·34 (95% CI 2·01-2·73; p<0·0010) with clinician-collected tests, and 1·08 (0·74-1·52; p=0·68) when screened with self-collection tests, after controlling for age and health insurance status. Screening coverage was similar in both periods (52·7% vs 53·2%); improvements of programmatic indicators were observed in the HPV testing period in relation to laboratory centralisation, lower overscreening (6·6% vs 0·0%), higher adherance to age recommendations (79·3% vs 98·8%), and a decrease of inadequate samples (3·6% vs 0·2%). INTERPRETATION: HPV testing in middle-income settings increases detection of CIN2+ lesions and allows for improvement of programmatic indicators. Evidence suggests that the introduction of HPV testing will accelerate the reduction of cervical cancer burden. FUNDING: Argentinian National Cancer Institute and National Council of Scientific and Technologic Research.

14.
Papillomavirus Res ; 7: 112-117, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30851448

RESUMO

INTRODUCTION: In recent years, an association between HPV-16 and oropharyngeal cancers has been reported. Therefore, it is necessary to evaluate whether vaccination decreases the exposure of HPV-16 in the oral cavity. OBJECTIVE: To evaluate the effect of vaccination on oral HPV-16 infection in high school students in the city of Cali, Colombia. METHODS: In this cross-sectional study, HPV-16 DNA was detected in samples from the oral cavity and throat of 1,784 high school students of both genders, aged 14-17 years old, in 21 schools in the city of Cali, Colombia. The number in vaccinated girls were 944 vs., 95 unvaccinated girls and 745 unvaccinated boys. RESULTS: The HPV exposure percentages were: 0.7% in vaccinated girls, 3.2% in unvaccinated girls and 2.3% in unvaccinated boys. The odds ratio (OR) of detection of HPV-16 in vaccinated versus unvaccinated students was 0.28 (95% CI: 0.07-0.88), representing a 72% reduction in HPV-16 detection in students immunized with two doses. The odds of detection of HPV-16 in unvaccinated male students were 3.6 times those of vaccinated girls (OR = 3.6, 95% CI: 1.21-12.81) and increased to almost eight-fold in boys who had initiated sexual activity (OR = 7.74, 95% CI: 1.53-75.09). CONCLUSIONS: HPV vaccination was associated with the reduction of HPV-16 exposure percentages in the oral and oropharyngeal cavity.


Assuntos
Papillomavirus Humano 16/isolamento & purificação , Doenças da Boca/epidemiologia , Doenças da Boca/prevenção & controle , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Adolescente , Cidades/epidemiologia , Colômbia/epidemiologia , Estudos Transversais , DNA Viral/análise , Feminino , Papillomavirus Humano 16/imunologia , Humanos , Masculino , Boca/virologia , Doenças da Boca/virologia , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Faringe/virologia , Estudantes , Resultado do Tratamento
15.
Int J Cancer ; 145(8): 2042-2050, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30684396

RESUMO

HPV testing is a better alternative for cervical cancer screening, but additional procedures are required for triage of HPV positive women. HPV encoded oncoproteins E6 and E7, as the main effectors of HPV carcinogenicity represent promising triage alternatives. To evaluate performance of the test, we included 155 women from a screening study and 59 from the same referral population attending colposcopy and with precancerous lesions. All were HPV-tested with HC2 and genotyped with LiPA, and cervical swabs were tested for HPV16/18 E6 oncoproteins. Histologic specimens were reviewed and adjudicated using p16 immunohistochemistry and 55 women had confirmed histologic HSIL, 31 (56.3%) associated with HPV 16/18, 23 with other HPV types and one HPV negative. Sensitivity and specificity were estimated with histologic HSIL/cancer as gold standard. E6 oncoprotein was detectable in all but one HSIL and in all cancers where HPV16/18 DNA was detected, but in none of the cases associated with other HPV types or HPV negatives. Among the few HPV16/18 DNA positive subjects initially without HSIL (n = 4) who were E6 oncoprotein positive, precancer was detected during follow-up in 2 out of 3 with available information. Estimated sensitivity for HPV16/18-related HSIL+ was 96.8% (95%CI = 83.8-99.8) and for all HSIL+ regardless of HPV type it was 56.4% (95%CI = 43.3-68.6). Specificity was 97.5% (95%CI = 93.7-99.0). E6 oncoprotein proved as a highly sensitive and specific marker for detection of HPV16/18-related HSIL lesions in this Honduran population with limited previous screening and may be useful as a triage method in screening programs, particularly in low income countries.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Proteínas de Ligação a DNA/genética , Detecção Precoce de Câncer/métodos , Proteínas Oncogênicas Virais/genética , Infecções por Papillomavirus/diagnóstico , Proteínas Repressoras/genética , Neoplasias do Colo do Útero/diagnóstico , Adulto , Neoplasia Intraepitelial Cervical/virologia , DNA Viral/genética , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase/métodos , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/virologia , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/virologia
16.
J Natl Cancer Inst ; 111(9): 923-932, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30629194

RESUMO

BACKGROUND: Human papillomavirus vaccination and cervical screening are lacking in most lower resource settings, where approximately 80% of more than 500 000 cancer cases occur annually. Visual inspection of the cervix following acetic acid application is practical but not reproducible or accurate. The objective of this study was to develop a "deep learning"-based visual evaluation algorithm that automatically recognizes cervical precancer/cancer. METHODS: A population-based longitudinal cohort of 9406 women ages 18-94 years in Guanacaste, Costa Rica was followed for 7 years (1993-2000), incorporating multiple cervical screening methods and histopathologic confirmation of precancers. Tumor registry linkage identified cancers up to 18 years. Archived, digitized cervical images from screening, taken with a fixed-focus camera ("cervicography"), were used for training/validation of the deep learning-based algorithm. The resultant image prediction score (0-1) could be categorized to balance sensitivity and specificity for detection of precancer/cancer. All statistical tests were two-sided. RESULTS: Automated visual evaluation of enrollment cervigrams identified cumulative precancer/cancer cases with greater accuracy (area under the curve [AUC] = 0.91, 95% confidence interval [CI] = 0.89 to 0.93) than original cervigram interpretation (AUC = 0.69, 95% CI = 0.63 to 0.74; P < .001) or conventional cytology (AUC = 0.71, 95% CI = 0.65 to 0.77; P < .001). A single visual screening round restricted to women at the prime screening ages of 25-49 years could identify 127 (55.7%) of 228 precancers (cervical intraepithelial neoplasia 2/cervical intraepithelial neoplasia 3/adenocarcinoma in situ [AIS]) diagnosed cumulatively in the entire adult population (ages 18-94 years) while referring 11.0% for management. CONCLUSIONS: The results support consideration of automated visual evaluation of cervical images from contemporary digital cameras. If achieved, this might permit dissemination of effective point-of-care cervical screening.

17.
J Infect Dis ; 219(1): 41-49, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30085139

RESUMO

Background: There are limited data regarding the duration of immunity induced by different human papillomavirus (HPV) vaccination schedules and the immunogenicity of a booster dose of both bivalent HPV vaccine (bHPV) or quadrivalent HPV vaccine (qHPV). Methods: Follow-up of a nonrandomized clinical trial to evaluate the 5-year antibody persistence of the bHPV in girls (age, 9-10 years) and women (age, 18-24 years). Noninferiority of the 2-dose versus 3-dose schedule among girls was evaluated at months 54 (n = 639) and 64 (n = 990). Girls vaccinated with a 2-dose schedule of bHPV or qHPV received a booster dose of either vaccine at month 61. Immunogenicity was measured using a virus-like particle-based enzyme-linked immunosorbent assay. Geometric mean titers (GMTs) for HPV16/18 were estimated after stratification by vaccination schedule and age group. Results: At months 54 and 64, the 2-dose schedule remained noninferior to the 3-dose schedule. GMTs remained above natural infection levels across all age groups up to 64 months. After the booster, anti-HPV16/18 GMTs increased exponentially with the same pattern, regardless of vaccine administered. No safety concerns were identified with the booster dose. Conclusions: A 2-dose schedule is highly immunogenic in girls, suggesting a high immune memory. Thus, a booster dose is likely to be unprofitable, considering the low global immunization coverage. Clinical Trials Registration: NCT01717118.


Assuntos
Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/imunologia , Imunização Secundária , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Vacinação , Adolescente , Anticorpos Antivirais/sangue , Criança , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/administração & dosagem , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Humanos , Esquemas de Imunização , Ensaios Clínicos Controlados não Aleatórios como Assunto , Infecções por Papillomavirus/sangue , Infecções por Papillomavirus/imunologia , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/sangue , Adulto Jovem
19.
PLoS Pathog ; 14(11): e1007352, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30383862

RESUMO

Recent discoveries on the origins of modern humans from multiple archaic hominin populations and the diversity of human papillomaviruses (HPVs) suggest a complex scenario of virus-host evolution. To evaluate the origin of HPV pathogenesis, we estimated the phylogeny, timing, and dispersal of HPV16 variants using a Bayesian Markov Chain Monte Carlo framework. To increase precision, we identified and characterized non-human primate papillomaviruses from New and Old World monkeys to set molecular clock models. We demonstrate specific host niche adaptation of primate papillomaviruses with subsequent coevolution with their primate hosts for at least 40 million years. Analyses of 212 HPV16 complete genomes and 3582 partial sequences estimated ancient divergence of HPV16 variants (between A and BCD lineages) from their most recent common ancestors around half a million years ago, roughly coinciding with the timing of the split between archaic Neanderthals and modern Homo sapiens, and nearly three times longer than divergence times of modern Homo sapiens. HPV16 A lineage variants were significantly underrepresented in present African populations, whereas the A sublineages were highly prevalent in European (A1-3) and Asian (A4) populations, indicative of viral sexual transmission from Neanderthals to modern non-African humans through multiple interbreeding events in the past 80 thousand years. Remarkably, the human leukocyte antigen B*07:02 and C*07:02 alleles associated with increased risk in cervix cancer represent introgressed regions from Neanderthals in present-day Eurasians. The archaic hominin-host-switch model was also supported by other HPV variants. Niche adaptation and virus-host codivergence appear to influence the pathogenesis of papillomaviruses.


Assuntos
Papillomavirus Humano 16/genética , Papillomavirus Humano 16/patogenicidade , Adaptação Fisiológica/genética , Animais , Evolução Biológica , Evolução Molecular , Fósseis , Variação Genética/genética , Hominidae/imunologia , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Papillomaviridae/genética , Papillomaviridae/patogenicidade , Papillomaviridae/fisiologia , Filogenia
20.
J Glob Oncol ; 4: 1-8, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30241265

RESUMO

Overwhelmed by an abundance of often confusing, ambiguous, or apparently contradictory messages on disease prevention in today's multiple media streams, the general public would surely value authoritative, clear, and evidence-based instructions on how to actively contribute to the reduction of their cancer risk. The European Code Against Cancer is a set of 12 recommendations for individuals on how to reduce cancer risk. The Code carries the authority and reliability of expert scientists working under the coordination of the International Agency for Research on Cancer, the cancer research agency of the WHO. The Code's messages are aimed at individuals and have been enthusiastically promoted by European cancer associations. The experience of developing and promoting the European Code has generated interest in developing analogous recommendations for other regions of the world. Under the overall umbrella of a World Code Against Cancer using the same International Agency for Research on Cancer methodology, regional Codes could be developed, focused on regions sufficiently large and distinct to merit development of versions adapted to regional differences in risk factors and cancer patterns. Consideration of such an adapted model illustrates why a simple translation of the European Code would not be sufficient to promote cancer prevention globally.


Assuntos
Neoplasias/epidemiologia , Assistência à Saúde , Saúde Global , Guias como Assunto , Humanos , Incidência , Mortalidade , Vigilância em Saúde Pública , Fatores de Risco
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