HPV distribution in cervical cancer in Portugal. A retrospective study from 1928 to 2005

Objectives: To determine human papillomavirus (HPV) types in invasive cervical cancer in Portugal. Methods: Cases diagnosed at the Institute Portugues de Oncologia de Lisboa de Francisco Gentil from the year 1928 to 2005 were selected for HPV DNA detection and genotyping using SPF10/DEIA/LiPA25 system. Results: Of the 1214 samples that were considered appropriate for HPV detection, 714 (58.8%; 95% CI: 56.0-61.6%) were positive for HPV DNA. This detection rate varied being lower in the first 3 decades (31.3%; 50.1%; 46.5%) and higher in the last decades (77.4-95.1%). This difference was due probably to the fixative used in the first three decades. The five most common types identified among HPV positive cases were HPV16 (58.2%), HPV18 (9.2%), HPV33 (6.2%), HPV45 (4.7%) and HPV31 (4.4%). Multiple infections were detected in 2.8% of the cases. HPV16 and 18 accounted for 67.4% of infections. There were no statistically significant changes of these types over the studied period. An increase at patient's age at diagnosis was observed in the last decades (p < 0.001). Conclusion: HPV16 and 18 accounts for almost 70% of cervical cancers in all 9 decades studied and support data that effective vaccination against these 2 types will reduce the cervical burden in Portuguese women

Estimation of the overall burden of cancers, precancerous lesions, and genital warts attributable to 9-valent HPV vaccine types in women and men in Europe

Background: In addition to cervical cancer, human papillomavirus (HPV) is responsible for a significant proportion of cancers and precancerous lesions of the vulva, vagina, anus, penis, head and neck, as well as genital warts. We estimated the annual number of new cases of these diseases attributable to 9-valent HPV vaccine types in women and men in Europe. Methods: The annual number of new cancers of the cervix, vulva, vagina, anus, penis, and selected head and neck sites in the population of the European Medicines Agency territory was estimated based on age-specific incidence rates extracted from Cancer Incidence in 5 Continents, Volume X and Eurostat population data for 2015. The annual number of new cancers attributable to 9-valent HPV vaccine types was estimated by applying the HPV attributable fraction from reference publications based on a large European multicenter study. For non-cervical cancers, HPV attributable fractions were based on oncogenically-active HPV infections only (i.e., detection of HPV DNA and either mRNA and/or p16 positivity). For precancerous lesions of the cervix, vulva, vagina, and anus, and for genital warts, previously published estimations were updated for the 2015 population. Results: The annual number of new cancers attributable to 9-valent HPV vaccine types was estimated at 47,992 (95% bound: 39,785-58,511). Cervical cancer showed the highest burden (31,130 cases), followed by head and neck cancer (6,786 cases), anal cancer (6,137 cases), vulvar cancer (1,466 cases), vaginal cancer (1,360 cases), and penile cancer (1,113 cases). About 81% were estimated to occur in women and 19% in men. The annual number of new precancerous lesions (CIN2+, VIN2/3, VaIN2/3, and AIN2/3) and genital warts attributable to 9-valent HPV vaccine types was estimated at 232,103 to 442,347 and 680,344 to 844,391, respectively. Conclusions: The burden of cancers associated with 9-valent HPV vaccine types in Europe is substantial in both sexes. Head and neck cancers constitute a heavy burden, particularly in men. Overall, about 90% of HPV-related cancers, 80% of precancerous lesions, and 90% of genital warts are expected to be attributable to 9-valent HPV vaccine types each year, demonstrating the important preventive potential of the 9-valent HPV vaccine in Europe

The impact of p16(ink4a) positivity in invasive vulvar cancer on disease-free and disease-specific survival, a retrospective study

Purpose To evaluate HPV and p16(ink4a) status as prognostic factors in patients with invasive vulvar cancer. Methods Retrospective analysis of disease-free (DFS) and disease-specific survival (DSS) of patients with invasive vulvar cancer at a single tertiary care center. Histology, HPV and p16(ink4a) status were evaluated in the context of a global multicenter trial. Logistic regression models were performed to identify the impact of p16(ink4a) positivity. Results 135 patients were included in the analysis. 32 (23.7%) showed a p16(ink4a) expression of over 25%. Disease-free and disease-specific survival was longer in p16(ink4a) positive patients (23 vs. 10 months, p = 0.004, respectively, 29 vs. 21 months, p = 0.016). In multivariate analysis, p16(ink4a) positivity was an independent parameter for DFS (p = 0.025, HR: 2.120 (1.100-4.085)), but not for DSS (p = 0.926, HR: 1.029 (0.558-1.901), in contrast to age and tumor stage. Conclusions Age and tumor stage negatively affect survival. However, disease-free survival is significantly longer in patients with p16(ink4a) positive invasive vulvar cancer

Immune biomarkers of response to immune-checkpoint inhibitors in head and neck squamous cell carcinoma

Anti-programmed cell death protein 1 (PD-1) agents have become the standard of care for platinum-refractory recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) and are currently being evaluated in various disease settings. However, despite the gain in overall survival seen in some of the clinical trials, the majority of patients display primary resistance and do not benefit from these agents. Taking into consideration the potentially severe immune-related toxicities and their high cost, the search for predictive biomarkers of response is crucial. Besides Programmed death ligand-1 (PD-L1) expression, other biomarkers such as immune infiltration, tumor mutational burden or immune-gene expression profiling have been explored, but none of them has been validated in this disease. Among these, the microbiota has recently garnered tremendous interest since it has proven to influence the efficacy of PD-1 blockade in some tumor types. With the accumulating evidence on the effect of the microbiota in HNSCC tumorigenesis and progression, the study of its potential role as a predictive immune biomarker is warranted. This review examines the available evidence on emerging immune predictive biomarkers of response to anti-PD-1/PD-L1 therapy in HNSCC, introducing the microbiota and its potential use as a predictive immune biomarker in this disease

Might Oral Human Papillomavirus (HPV) Infection in Healthy Individuals Explain Differences in HPV-Attributable Fractions in Oropharyngeal Cancer? A Systematic Review and Meta-analysis

Background. Differences in oral human papillomavirus (HPV) prevalence and contrasts in HPV-attributable fractions (AFs) in oropharyngeal cancer (OPC) have not been evaluated in depth. Methods. A systematic review was performed to identify studies in which at least 50 healthy individuals were tested for oral HPV infection. Information on sex, age, tobacco/alcohol consumption, sex practices, specimen collection, HPV detection, and population type was extracted. Prevalences were pooled using random-effects models for meta-analyses of binomial data. Correlations were assessed by the Spearman test. Results. Forty-eight reports comprising 28 544 individuals fulfilled inclusion criteria. Global oral HPV prevalence was 4.9%. Estimates were highest in Europe, although regional differences were not statistically significant. HPV16 prevalence was 1.0% globally, and regional differences became statistically significant. A lifetime history of >6 sex partners showed a higher risk of oral HPV infection. The age-specific HPV distribution revealed a prevalence of >= 5% over 40 years of age and a lower prevalence at younger ages. There was no association between oral HPV prevalence and HPV-AFs or age-standardized rates (ASRs) of OPC, genital HPV in healthy women, or tobacco use. Conclusions. Differences in HPV-AFs or ASRs of OPC cannot be explained by differences in the prevalence of oral HPV infection across healthy populations. Consistent research on determinants of oral HPV prevalence, acquisition, clearance, and persistence is warranted

Potential impact of a nine-valent vaccine in human papillomavirus related cervical disease

Background: Information on human papillomavirus (HPV) type distribution is necessary to evaluate the potential impact of current and future HPV vaccines. We estimated the relative contribution (RC) to invasive cervical cancer (ICC) and precancerous cervical lesions of the nine HPV types (HPV 6/11/16/18/31/33/45/52/58) included in an HPV vaccine currently under development. Methods: Estimations on ICC were based on an international study of 8,977 HPV positive cases and estimations on precancerous cervical lesions were extracted from a published meta-analysis including 115,789 HPV positive women. Globocan 2008 and 2010 World Population Prospects were used to estimate current and future projections of new ICC cases. Results: RC of the 9 HPV types in ICC was 89.4%, with 18.5% of cases positive for HPV 31/33/45/52/58. Regional variations were observed. RCs varied by histology, ranging between 89.1% in squamous cell carcinomas (SCC) and 95.5% in adenocarcinomas (ADC). HPV 16/18/45 were detected in 94.2% of ADC. RC of the 9 types altogether decreased with age (trend test p < 0.0001), driven by the decrease in older ages of HPV 16/18/45. In contrast, the RC of HPV 31/33/52/58 increased with age. Due to population growth alone, projected estimates of ICC cases attributable to the 9 types are expected to rise from 493,770 new cases in 2012 to 560,887 new cases in 2025. The RCs of individual high risk HPV types varied by cytological and histological grades of HPV-positive precancerous cervical lesions, and there was an under representation of HPV 18 and 45 compared to ICC. Conclusions: The addition of HPV 31/33/45/52/58 to HPV types included in current vaccines could prevent almost 90% of ICC cases worldwide. If the nine-valent vaccine achieves the same degree of efficacy than previous vaccines, world incidence rates could be substantially reduced

Problemas relacionados con la medicación que causan ingresos hospitalarios

ResumenObjetivoLos problemas relacionados con los medicamentos (PRM) están vinculados al tratamiento farmacológico del paciente e interfieren o pueden interferir con los resultados esperados en su salud. El presente estudio tiene como objetivo determinar la prevalencia de los PRM en los pacientes de un centro de salud urbano que son causa de ingreso en su hospital de referencia, y su evitabilidad.DiseñoEs un estudio observacional de tipo descriptivo y retrospectivo.EmplazamientoCENTRO de Salud Les Corts, que es un centro de salud urbano y docente con una población asignada de 32.318 habitantes.ParticipantesUsuarios del CS Les Corts ingresados en el Hospital Clínico de Barcelona desde agosto de 2005 a enero de 2006.Resultados y mediciones principalesUna pareja de un farmacéutico y un médico de familia analizan las historias clínicas y determinan la presencia o no de PRM. El 13,4% de todas las altas presentan PRM, que en su mayoría están implicados en el ingreso hospitalario (12%). Un 57,3% del total de altas con un PRM como causa del ingreso hospitalario se ha considerado evitable. Los ingresos por PRM se concentran en los servicios de medicina interna, cardiología y neumología. Los problemas de salud motivo de ingreso hospitalario por PRM son mayoritariamente circulatorios (38,5%) y respiratorios (11,5%).ConclusionesEl número de ingresos debidos a problemas relacionados con la medicación es elevado y evitable.AbstractObjectiveDrug related problems (DRP) are health problems associated with the pharmacological treatment of patients and interfere or can interfere with the expected results on their health. The aim of this study is to determine the prevalence of DRP in patients from an urban health centre that lead to hospitalisation, and its prevention.DesignIt is a retrospective, observational and descriptive study.SettingLes Corts Health Centre (HC), which is an urban health and teaching centre with a reference population of 32,318 inhabitants.ParticipantsUsers of the les Corts HC admitted to the Barcelona Hospital Clinic from August 2005 to January 2006.Results and main outcome measurementsA pharmacist and a family doctor analysed the clinical histories and determined whether or not there was a DRP. A DRP was present in 13.4% of all hospital discharges, and 12% were implicated in the hospital admission. It was considered that 57.3% of all the discharges with a DRP as the causing factor in the hospital admission were avoidable. Admissions due to DRP were mainly in internal medicine, cardiology and pneumology. The health problems that lead to hospital admission due to DRP are mainly circulatory (38.5%) and respiratory (11.5%).ConclusionsThe number of hospital admissions due to drug related problems is avoidably high

Association of antiretroviral therapy with anal high-risk human papillomavirus, anal intraepithelial neoplasia, and anal cancer in people living with HIV: a systematic review and meta-analysis.

BACKGROUND: The effect of antiretroviral therapy (ART) on the natural history of anal high-risk HPV and anal lesion progression is not well established. We reviewed the association of ART and other HIV-related factors on anal HPV infection, anal intraepithelial neoplasia (AIN), and anal cancer among people living with HIV. METHODS: For this systematic review and meta-analysis, we searched MEDLINE and EMBASE for studies published between Jan 1, 1996, and Oct 30, 2019, that reported the association of HIV-related exposures (ART or highly active ART [HAART], HIV-RNA plasma viral load [PVL], and nadir or current CD4 cell count) with outcomes of anal high-risk HPV prevalence, incidence, and persistence; prevalence, incidence, progression, or regression of anal histological and cytological abnormalities; and anal cancer incidence. Effect estimates were extracted whenever available; otherwise, they were calculated from raw data. We assessed the risk of bias of included studies using the Newcastle-Ottawa scale, and random-effects meta-analyses were done to examine heterogeneity using the I2 statistic. This study is registered on the PROSPERO database, CRD42018007271. FINDINGS: We identified 6777 studies, of which 5377 were excluded before full-text review. 122 studies providing estimates for 130 distinct populations matched the inclusion criteria. The populations comprised 417 006 people living with HIV (women, men who have sex with men, and men who have sex with women). 41 (32%) population estimates were not stratified by sex or sexual orientation. People living with HIV receiving ART had 35% lower high-risk HPV prevalence than ART-naive people (crude odds ratio [OR] 0·65, 95% CI 0·54-0·79; I2 12·1%, p=0·31) in 18 studies, and prolonged ART use was associated with a 10% reduction per year in high-risk HPV prevalence in two studies (adjusted OR 0·90, 0·85-0·95; I2 0%, p=0·88). People living with HIV with undetectable PVL had lower HSIL-AIN2+ prevalence than those with detectable PVL (crude OR 0·84, 0·72-0·98; I2 0%, p=0·80) in 16 studies, particularly if sustained for more than 1 year (crude OR 0·62, 0·47-0·81; I2 0%, p=0·51). ART was not associated with anal cancer incidence when adjusted for years living with HIV in three studies (adjusted hazard ratio [HR] 1·11, 95% CI 0·68-1·80; I2 0%, p=0·57), but ART users with sustained undetectable HIV PVL had 44% lower risk of anal cancer than those without (adjusted HR 0·56, 0·44-0·70; I2 0%, p=0·94) and for each increase in nadir CD4 cell counts of 100 cells per μL, there was a 40% decrease in anal cancer incidence (crude HR 0·60, 0·46-0·78; I2 21·7%, p=0·26). INTERPRETATION: Effective ART use and early initiation at high nadir CD4 counts might reduce anal high-risk HPV infection and anal cancer risk. Although most studies were cross-sectional in design and few adjusted for potential confounders, this analysis provides comprehensive estimates of the effect of ART and HIV-related factors on the natural history of anal HPV-related disease in people living with HIV. FUNDING: EU Marie Skłodowska-Curie Actions programme

Burden of Human papillomavirus (HPV)-related disease and potential impact of HPV vaccines in the Republic of Korea

Background: We aimed to review the burden and the potential impact of human papillomavirus (HPV) vaccines on HPV-related diseases in the Republic of Korea and to discuss cervical cancer prevention practices in this country. Methods: Cancer burden statistics were retrieved from GLOBOCAN-2018 and Statistics Korea. HPV disease burden was assessed via systematic review. Vaccine types relative contribution (RC) was estimated using data from an international project using formalin-fixed paraffin-embedded specimens. Results: Despite a downtrend in cervical cancer in recent years, Korean rates remain high. In contrast, oropharyngeal cancer incidence has gradually increased and other anogenital cancers remain rare. In Korea, HPV prevalence in general population is around 20%. In cervical cancer, RC of HPVs 16/18 (74.0%) increased to 92.0% when including HPVs 31/33/45/52/58. Limited information was available for other HPV-related cancer sites. Regarding prevention, since the inclusion of the HPV vaccine into the National Immunization Program, almost half (49%) of the target cohort in 2016 had received the first dose of vaccine. Further, percentage of women screened with pap has increased from 41.1%-2009 to 53.0%-2016. Conclusions: HPV-related disease burden in Korea is significant. Results suggest that the combination of effective and high coverage HPV vaccination and screening programmes could substantially impact on HPV-related disease in Korea

Competing mortality in oropharyngeal carcinoma according to HPV status

Purpose or Objective:The objective of the present study is to assess differences in the competing causes of death in oropharyngeal carcinoma (OPC) patients as a function of the HPV status