High‐risk human papillomavirus type 16/18 (HPV16/18) genotyping is unable to accurately discriminate nonprogressive infections from those that will progress to cervical cancer. Our study aimed to ...assesses if additional testing either with liquid‐based cytology (LBC) or the putative progression markers p16/Ki‐67 and HPV16/18 E6 oncoprotein (E6) can improve the efficiency of HPV16/18 genotyping for triaging high‐risk HPV (hrHPV)‐positive women through better cancer risk stratification. Women attending colposcopy after positive HPV16/18 genotyping results within the Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage (FRIDA) hrHPV‐based screening study in Tlaxcala, Mexico, underwent further testing with LBC, p16/Ki‐67 dual‐stained (DS) cytology and E6. We calculated measures of test performance for detecting histologically confirmed cervical intraepithelial neoplasia grade 2 or higher (CIN2+) and grade 3 or higher (CIN3+). A number of 475 (64.3%) of 739 HPV16/18‐positive women had complete results for all tests. Triage positivity rates were 14.1%, 18.5% and 24.4%, for LBC, E6 and DS, respectively. Compared with LBC, DS had higher sensitivity (24.4% vs 60.0%) although lower specificity (87.0% vs 79.3%) for CIN3+ (P < .001), whereas E6 had a sensitivity of 37.8% and a specificity of 83.5%. No invasive cancer was missed by DS or E6, but 75% were in normal cytology. DS test was associated with nearly 75% reduction of colposcopy referrals compared with the direct referral of all HPV16/18‐positive women, giving the least number of colposcopies (n = 4.3) per CIN3+ detected. We show that adjunctive testing of HPV16/18‐positive women with DS may greatly reduce unnecessary colposcopy referrals within HPV‐based screening employing HPV16/18 genotyping while retaining acceptable sensitivity for CIN2+ and CIN3+.
What's new?
Testing for HPV 16/18 is currently used in many screening programs for cervical cancer. However, standard HPV genotyping cannot determine whether or not the infection is likely to progress to cancer. In this study, the authors found that when dual‐stained cytology (DS) for p16/Ki‐67 is added to the screening, it may reduce unnecessary colposcopy referrals by as much as 75%. Meanwhile, this combination testing is also sensitive enough that invasive lesions can be caught early. This approach to HPV triage may thus be significantly more efficient, while reducing unnecessary procedures.
La alfabetización en salud es el proceso centrado en la obtención del conocimiento, la motivación y las competencias individuales para entender y acceder a información, expresar opiniones y tomar ...decisiones relacionadas con la promoción y el mantenimiento de la salud, lo que es aplicable en diferentes contextos, entornos y a lo largo de toda la vida. Esta perspectiva conceptual es muy necesaria ante la emergencia del virus SARS-CoV-2 que produce la enfermedad Covid-19, la cual ha producido una pandemia con efectos devastadores, no sólo desde el punto de vista de la salud, sino también, de manera muy importante, desde el económico, político y social. En este ensayo se tratan de establecer los elementos basados en la evidencia científica que orientan las políticas públicas de prevención y control, entre los que destacan: a) la inteligencia epidemiológica, la cual incluye no sólo la estrategia de vigilancia poblacional sino, ante la imposibilidad real de identificación de todos los casos positivos, la puesta en práctica de estrategias de vigilancia centinela y la vigilancia basada en eventos; b) las medidas de mitigación de la propagación de la epidemia, tales como distanciamiento social e higiene, lavado de manos, cuarentena, restricción de movimiento y utilización de cubrebocas, entre otras; c) medidas de supresión de la transmisión cuando el número de casos es muy elevado, como el endurecimiento de medidas drásticas de encierro en casa; d) fortalecimiento de la capacidad de atención médica en los sistemas de salud e incremento de la capacidad de prevención de la transmisión en los servicios de salud, incluyendo la utilidad de las pruebas diagnósticas; y e) el desarrollo de vacunas profilácticas contra Covid-19, así como la generación de agentes terapéuticos. Todas estas acciones no sólo deben implementarse rápidamente desde la perspectiva multidisciplinaria y multisectorial de la salud pública para contener, prevenir y controlar la epidemia, sino que necesitan obligatoriamente del concurso de la comunidad como responsabilidad compartida. Debido a todo esto, es necesaria la alfabetización en salud pública.
Summary Background Vaginal self-sampling for human papillomavirus (HPV) DNA testing could increase rates of screening participation. In clinic-based settings, vaginal HPV testing is at least as ...sensitive as cytology for detecting cervical intraepithelial neoplasia (CIN) grade 2 or worse; however, effectiveness in home settings is unknown. We aimed to establish the relative sensitivity and positive predictive value for HPV screening of vaginal samples self-collected at home as compared with clinic-based cervical cytology. Methods We did a community-based, randomised equivalence trial in Mexican women of low socioeconomic status aged 25–65 years. Participants came from 540 medically underserved, predominantly rural communities in Morelos, Guerrero, and the state of Mexico. Our primary endpoint was CIN 2 or worse, detected by colposcopy. We used a computer-generated randomisation sequence to randomly allocate patients to HPV screening or cervical cytology. Eight community nurses who were masked to patient allocation received daily lists of the women's names and addresses, and did the assigned home visits. We referred women with positive results in either test to colposcopy. We did per-protocol and intention-to-screen analyses. This trial was registered with the Instituto Nacional de Salud Pública, Mexico, INSP number 590. Findings 12 330 women were randomly allocated to HPV screening and 12 731 to cervical cytology; 9202 women in the HPV screening group adhered to the protocol, as did 11 054 in the cervical cytology group. HPV prevalence was 9·8% (95% CI 9·1–10·4) and abnormal cytology rate was 0·38% (0·23–0·45). HPV testing identified 117·4 women with CIN 2 or worse per 10 000 (95·2–139·5) compared with 34·4 women with CIN 2 or worse per 10 000 (23·4–45·3) identified by cytology; the relative sensitivity of HPV testing was 3·4 times greater (2·4–4·9). Similarly, HPV testing detected 4·2 times (1·9–9·2) more invasive cancers than did cytology (30·4 per 10 000 19·1–41·7 vs 7·2 per 10 000 2·2–12·3). The positive predictive value of HPV testing for CIN 2 or worse was 12·2% (9·9–14·5) compared with 90·5% (61·7–100) for cytology. Interpretation Despite the much lower positive predictive value for HPV testing of self-collected vaginal specimens compared with cytology, such testing might be preferred for detecting CIN 2 or worse in low-resource settings where restricted infrastructure reduces the effectiveness of cytology screening programmes. Because women at these sites will be screened only a few times in their lives, the high sensitivity of a HPV screen is of paramount importance. Funding Instituto Nacional de Salud Pública, the Health Ministry of Mexico, QiAGEN Corp
Summary Background Evidence from Europe, Asia, and North America suggests that standard three-drug regimens of a proton-pump inhibitor plus amoxicillin and clarithromycin are significantly less ...effective for eradication of Helicobacter pylori infection than are 5-day concomitant and 10-day sequential four-drug regimens that include a nitroimidazole. These four-drug regimens also entail fewer antibiotic doses than do three-drug regimens and thus could be suitable for eradication programmes in low-resource settings. Few studies in Latin America have been done, where the burden of H pylori -associated diseases is high. We therefore did a randomised trial in Latin America comparing the effectiveness of four-drug regimens given concomitantly or sequentially with that of a standard 14-day regimen of triple therapy. Methods Between September, 2009, and June, 2010, we did a randomised trial of empiric 14-day triple, 5-day concomitant, and 10-day sequential therapies for H pylori in seven Latin American sites: Chile, Colombia, Costa Rica, Honduras, Nicaragua, and Mexico (two sites). Participants aged 21–65 years who tested positive for H pylori by a urea breath test were randomly assigned by a central computer using a dynamic balancing procedure to: 14 days of lansoprazole, amoxicillin, and clarithromycin (standard therapy); 5 days of lansoprazole, amoxicillin, clarithromycin, and metronidazole (concomitant therapy); or 5 days of lansoprazole and amoxicillin followed by 5 days of lansoprazole, clarithromycin, and metronidazole (sequential therapy). Eradication was assessed by urea breath test 6–8 weeks after randomisation. The trial was not masked. Our primary outcome was probablity of H pylori eradication. Our analysis was by intention to treat. This trial is registered with ClinicalTrials.gov , registration number NCT01061437. Findings 1463 participants aged 21–65 years were randomly allocated a treatment: 488 were treated with 14-day standard therapy, 489 with 5-day concomitant therapy, and 486 with 10-day sequential therapy. The probability of eradication with standard therapy was 82·2% (401 of 488), which was 8·6% higher (95% adjusted CI 2·6–14·5) than with concomitant therapy (73·6% 360 of 489) and 5·6% higher (–0·04% to 11·6) than with sequential therapy (76·5% 372 of 486). Neither four-drug regimen was significantly better than standard triple therapy in any of the seven sites. Interpretation Standard 14-day triple-drug therapy is preferable to 5-day concomitant or 10-day sequential four-drug regimens as empiric therapy for H pylori infection in diverse Latin American populations. Funding Bill & Melinda Gates Foundation, US National Institutes of Health.
Gallbladder cancer is usually associated with gallstone disease, late diagnosis, unsatisfactory treatment, and poor prognosis. We report here the worldwide geographical distribution of gallbladder ...cancer, review the main etiologic hypotheses, and provide some comments on perspectives for prevention. The highest incidence rate of gallbladder cancer is found among populations of the Andean area, North American Indians, and Mexican Americans. Gallbladder cancer is up to three times higher among women than men in all populations. The highest incidence rates in Europe are found in Poland, the Czech Republic, and Slovakia. Incidence rates in other regions of the world are relatively low. The highest mortality rates are also reported from South America, 3.5–15.5 per 100,000 among Chilean Mapuche Indians, Bolivians, and Chilean Hispanics. Intermediate rates, 3.7 to 9.1 per 100,000, are reported from Peru, Ecuador, Colombia, and Brazil. Mortality rates are low in North America, with the exception of high rates among American Indians in New Mexico (11.3 per 100,000) and among Mexican Americans.
The main associated risk factors identified so far include cholelithiasis (especially untreated chronic symptomatic gallstones), obesity, reproductive factors, chronic infections of the gallbladder, and environmental exposure to specific chemicals. These suspected factors likely represent promoters of carcinogenesis. The main limitations of epidemiologic studies on gallbladder cancer are the small sample sizes and specific problems in quantifying exposure to putative risk factors. The natural history of gallbladder disease should be characterized to support the allocation of more resources for early treatment of symptomatic gallbladder disease in high–risk populations. Secondary prevention of gallbladder cancer could be effective if supported by cost–effective studies of prophylactic cholecystectomy among asymptomatic gallstone patients in high–risk areas.
Background
Men who have sex with men (MSM) are at high risk for oral human papillomavirus (HPV infection). There are no specific screening guidelines to facilitate the identification of people at ...risk for oral HPV infection. We aimed to estimate the prevalence of oral high‐risk HPV and create a risk score to identify MSM at higher risk for prevalent oral HPV.
Methods
We collected baseline data from a clinical trial from a subsample of 500 MSM attending sexually transmitted disease treatment clinics; they provided an oral gargle sample for high‐risk HPV detection. We calculated oral high‐risk HPV prevalence and 95% confidence intervals (CIs), used a logistic regression model to identify factors associated with high‐risk HPV infection, and created a risk score.
Results
The prevalence of any oral high‐risk HPV among MSM was 11.1% (95% CI: 8.6–14.2), with a higher prevalence observed among men living with HIV (14.8%). Factors independently associated with oral high‐risk HPV were age ≥40 years (OR = 2.71, 95% CI: 1.28–5.73 compared to <40 years), being HIV‐positive with CD4 count 200–499 (OR = 2.76, 95% CI: 1.34–5.65 compared to HIV‐negative), and recent recreational use of vasodilators (poppers/sildenafil) (OR = 2.02, 95% CI: 1.02–2.97). The risk score had good discriminatory power (AUC = 0.70, 95% CI: 0.63–0.77).
Conclusions
MSM have specific predictors for prevalent oral high‐risk HPV, and a risk score could be used by clinicians to target men with vaccine recommendations and counseling, and identify those who could benefit from primary interventions given the available resources, or for referral to dental services for follow‐up when available.
The control arm of the phase III VIVIANE (Human PapillomaVIrus: Vaccine Immunogenicity ANd Efficacy; NCT00294047) study in women >25 years was studied to assess risk of progression from cervical HPV ...infection to detectable cervical intraepithelial neoplasia (CIN). The risk of detecting CIN associated with the same HPV type as the reference infection was analysed using Kaplan–Meier and multivariable Cox models. Infections were categorised depending upon persistence as 6‐month persistent infection (6MPI) or infection of any duration. The 4‐year interim analysis included 2,838 women, of whom 1,073 (37.8%) experienced 2,615 infections of any duration and 708 (24.9%) experienced 1,130 6MPIs. Infection with oncogenic HPV types significantly increased the risk of detecting CIN grade 2 or greater (CIN2+) versus non‐oncogenic types. For 6MPI, the highest risk was associated with HPV‐33 (hazard ratio HR: 31.9 8.3–122.2, p < 0.0001). The next highest risk was with HPV‐16 (21.1 6.3–70.0, p < 0.0001). Similar findings were seen for infections of any duration. Significant risk was also observed for HPV‐18, HPV‐31, and HPV‐45. Concomitant HPV infection or CIN grade 1 or greater associated with a different oncogenic HPV type increased risk. Most women (79.3%) with an HPV infection at baseline cleared detectable infections of any duration, and 69.9% cleared a 6MPI. The risk of progression of HPV infection to CIN2+ in women >25 years in this study was similar to that in women 15–25 years in PATRICIA.
What's New?
Which HPV infections lead to cancer in women over 25 years? Most cervical cancer follows persistent oncogenic HPV infection, but most HPV infections clear naturally. Thus, to best predict patient outcomes, it's imperative to understand how HPV infections progress to CINs. This study confirmed that in women over 25 years, persistent infection with HPV‐33 or HPV‐16 meant the greatest chance of developing a CIN—the same as was found in women 15–25 years, in an earlier analysis.
Since cervical cancer remains common in Mexico despite an established cytology screening program, the Ministry of Health recently introduced pilot front‐line HPV testing into the Mexican cervical ...cancer screening program (CCSP). Here, we present the key field performance metrics of this population‐based study. High‐risk HPV DNA (hrHPV) testing was conducted on self‐collected vaginal specimens from 100,242 women aged 25–75 years residing in Morelos State. All hrHPV positive women and a random sample of 3.2% (n = 2,864) of hrHPV negative participants were referred for colposcopic examination. The main disease endpoint of interest was cervical intraepithelial neoplasia grade 2 or higher (CIN2+). We calculated relative risk, positive predictive value and negative predictive value adjusted for screening test verification bias. The overall prevalence of hrHPV was 10.8% (95%CI 10.6–11.0). Women positive for hrHPV had a relative risk of 15.7 for histologically detectable CIN2+. The adjusted positive predictive value of the hrHPV test was 2.4% (95%CI 2.1–2.7); whereas the adjusted negative predictive value was 99.8% (95%CI 99.8–99.9). These findings suggest that large‐scale vaginal hrHPV testing in a middle‐income country can identify women at greater risk of advanced cervical abnormalities in a programmatically meaningful way but care is warranted to ensure that disease not detectable at colposcopy is kept to a minimum. PASS shows areas that need improvement and sets the stage for wider use of hrHPV screening of self‐collected vaginal specimens in Mexico.
What's new?
DNA testing for high‐risk human papillomavirus (hrHPV) in self‐collected vaginal specimens may be useful for the routine detection of cervical precancers. In this investigation of 100,242 women in Mexico, DNA testing of self‐collected vaginal specimens was found to have an adjusted positive predictive value of 2.4% and an adjusted negative predictive value of 99.8%. The study sheds light on potential scale‐up problems associated with HPV DNA testing and reveals that a triage test is needed to prevent excessive referrals of women to limited colposcopy services.
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