Author
Beatriz Quirós
Bio: Beatriz Quirós is an academic researcher from University of Barcelona. The author has contributed to research in topics: Papillomaviridae & Cervical cancer. The author has an hindex of 14, co-authored 17 publications receiving 1368 citations.
Topics: Papillomaviridae, Cervical cancer, HPV vaccines, Cervix, Anal cancer
Papers
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German Cancer Research Center1, University of Barcelona2, National University of Colombia3, Manchester Royal Infirmary4, Charles University in Prague5, University of Ljubljana6, Universidad Nacional de Asunción7, University of Birmingham8, Université de Montréal9, Pompeu Fabra University10, Mexican Social Security Institute11, Catholic University of Korea12, University of Lagos13, Bangabandhu Sheikh Mujib Medical University14, Hospital General de México15, NewYork–Presbyterian Hospital16, Gomel State Medical University17, Instituto Português de Oncologia Francisco Gentil18, University of the Philippines19, Koç University20, Hacettepe University21, Indian Council of Medical Research22, University of Hawaii23, Cedars-Sinai Medical Center24, Hospital General San Juan de Dios25, Universidad Nacional Autónoma de Honduras26, Bayero University Kano27, Central University of Venezuela28, University of Chile29, Instituto Potosino de Investigación Científica y Tecnológica30
TL;DR: This large international study to estimate fractions of head and neck cancers attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation confirms the important role ofHPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs.
Abstract: BACKGROUND:
We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation.
METHODS:
Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results.
RESULTS:
A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America.
CONCLUSIONS:
HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs.
548 citations
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Mexican Social Security Institute1, NewYork–Presbyterian Hospital2, Instituto Português de Oncologia Francisco Gentil3, Universidad Nacional de Asunción4, Cedars-Sinai Medical Center5, University of Hawaii6, Charles University in Prague7, University of Iowa8, University of Ljubljana9, Jagiellonian University Medical College10, Université de Montréal11, German Cancer Research Center12
TL;DR: In view of the results of HPV DNA and high proportion of p16INK4a overexpression, infection by HPV is most likely to be a necessary cause for anal cancers in both men and women.
Abstract: Knowledge about human papillomaviruses (HPV) types involved in anal cancers in some world regions is scanty. Here, we describe the HPV DNA prevalence and type distribution in a series of invasive anal cancers and anal intraepithelial neoplasias (AIN) grades 2/3 from 24 countries. We analyzed 43 AIN 2/3 cases and 496 anal cancers diagnosed from 1986 to 2011. After histopathological evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping was performed using SPF-10/DEIA/LiPA25 system (version 1). A subset of 116 cancers was further tested for p16(INK4a) expression, a cellular surrogate marker for HPV-associated transformation. Prevalence ratios were estimated using multivariate Poisson regression with robust variance in the anal cancer data set. HPV DNA was detected in 88.3% of anal cancers (95% confidence interval [CI]: 85.1-91.0%) and in 95.3% of AIN 2/3 (95% CI: 84.2-99.4%). Among cancers, the highest prevalence was observed in warty-basaloid subtype of squamous cell carcinomas, in younger patients and in North American geographical region. There were no statistically significant differences in prevalence by gender. HPV16 was the most frequent HPV type detected in both cancers (80.7%) and AIN 2/3 lesions (75.4%). HPV18 was the second most common type in invasive cancers (3.6%). p16(INK4a) overexpression was found in 95% of HPV DNA-positive anal cancers. In view of the results of HPV DNA and high proportion of p16(INK4a) overexpression, infection by HPV is most likely to be a necessary cause for anal cancers in both men and women. The large contribution of HPV16 reinforces the potential impact of HPV vaccines in the prevention of these lesions.
267 citations
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Universidad Nacional de Asunción1, German Cancer Research Center2, Norfolk and Norwich University Hospital3, Mexican Social Security Institute4, Charles University in Prague5, Hospital General San Juan de Dios6, Instituto Português de Oncologia Francisco Gentil7, University of the Philippines8, University of Crete9, Westmead Hospital10, University of Chile11, Central University of Venezuela12, Jagiellonian University Medical College13, Eduardo Mondlane University14, Instituto Potosino de Investigación Científica y Tecnológica15, University of Hawaii16, Cedars-Sinai Medical Center17
TL;DR: About a third to a fourth of penile cancers were related to HPV when considering HPV DNA detection alone or adding an HPV activity marker, respectively, and the observed HPV type distribution reinforces the potential benefit of current and new HPV vaccines in the reduction of HPV-related penile neoplastic lesions.
189 citations
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TL;DR: The addition of HPVs 31/33/45/52/58 to HPV types included in current vaccines (HPV16/18) could prevent almost 90% of HPV positive female anogenital lesions worldwide and take into account that most HPV-related cancers are ICC ones, the 9-valent HPV vaccine could potentially avoid almost 88% of all female anogenic cancers.
174 citations
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Mexican Social Security Institute1, Medical University of Vienna2, Federal University of Rio de Janeiro3, French Institute of Health and Medical Research4, Westmead Hospital5, Jagiellonian University Medical College6, Eduardo Mondlane University7, University of Chile8, Medical University of Lublin9, Hospital General San Juan de Dios10, Manchester Royal Infirmary11, Instituto Potosino de Investigación Científica y Tecnológica12, German Cancer Research Center13
TL;DR: HPV was identified in a large proportion of invasive vaginal cancers and in almost all VAIN 2/3 and the most common type detected, HPV16 was the most frequently type detected in both precancerous and cancerous lesions.
145 citations
Cited by
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University of Pittsburgh1, University of Texas MD Anderson Cancer Center2, Stanford University3, University of Duisburg-Essen4, University of Chicago5, Institut Gustave Roussy6, University of Michigan7, Emory University8, Complutense University of Madrid9, Harvard University10, University of Zurich11, Kobe University12, Bristol-Myers Squibb13, Ohio State University14
TL;DR: Among patients with platinum-refractory, recurrent squamous-cell carcinoma of the head and neck, treatment with nivolumab resulted in longer overall survival than treatment with standard, single-agent therapy.
Abstract: BackgroundPatients with recurrent or metastatic squamous-cell carcinoma of the head and neck after platinum chemotherapy have a very poor prognosis and limited therapeutic options. Nivolumab, an anti–programmed death 1 (PD-1) monoclonal antibody, was assessed as treatment for this condition. MethodsIn this randomized, open-label, phase 3 trial, we assigned, in a 2:1 ratio, 361 patients with recurrent squamous-cell carcinoma of the head and neck whose disease had progressed within 6 months after platinum-based chemotherapy to receive nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks or standard, single-agent systemic therapy (methotrexate, docetaxel, or cetuximab). The primary end point was overall survival. Additional end points included progression-free survival, rate of objective response, safety, and patient-reported quality of life. ResultsThe median overall survival was 7.5 months (95% confidence interval [CI], 5.5 to 9.1) in the nivolumab group versus 5.1 months (95% CI, 4.0 to...
3,246 citations
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TL;DR: The preponderant burden of HPV16/18 and the possibility of cross‐protection emphasize the importance of the introduction of more affordable vaccines in less developed countries.
Abstract: HPV is the cause of almost all cervical cancer and is responsible for a substantial fraction of other anogenital cancers and oropharyngeal cancers. Understanding the HPV-attributable cancer burden can boost programs of HPV vaccination and HPV-based cervical screening. Attributable fractions (AFs) and the relative contributions of different HPV types were derived from published studies reporting on the prevalence of transforming HPV infection in cancer tissue. Maps of age-standardized incidence rates of HPV-attributable cancers by country from GLOBOCAN 2012 data are shown separately for the cervix, other anogenital tract and head and neck cancers. The relative contribution of HPV16/18 and HPV6/11/16/18/31/33/45/52/58 was also estimated. 4.5% of all cancers worldwide (630,000 new cancer cases per year) are attributable to HPV: 8.6% in women and 0.8% in men. AF in women ranges from 20% in India and sub-Saharan Africa. Cervix accounts for 83% of HPV-attributable cancer, two-thirds of which occur in less developed countries. Other HPV-attributable anogenital cancer includes 8,500 vulva; 12,000 vagina; 35,000 anus (half occurring in men) and 13,000 penis. In the head and neck, HPV-attributable cancers represent 38,000 cases of which 21,000 are oropharyngeal cancers occurring in more developed countries. The relative contributions of HPV16/18 and HPV6/11/16/18/31/33/45/52/58 are 73% and 90%, respectively. Universal access to vaccination is the key to avoiding most cases of HPV-attributable cancer. The preponderant burden of HPV16/18 and the possibility of cross-protection emphasize the importance of the introduction of more affordable vaccines in less developed countries.
1,268 citations
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TL;DR: It became apparent that HNSCC is a disease characterized by frequent mutations that create neoantigens, indicating that immunotherapies might be effective and that immunotherapy trials with immune checkpoint inhibitors were published, and these may be considered as a paradigm shift in head and neck oncology.
Abstract: Head and neck squamous cell carcinomas (HNSCCs) arise in the mucosal linings of the upper aerodigestive tract and are unexpectedly heterogeneous in nature. Classical risk factors are smoking and excessive alcohol consumption, and in recent years, the role of human papillomavirus (HPV) has emerged, particularly in oropharyngeal tumours. HPV-induced oropharyngeal tumours are considered a separate disease entity, which recently has manifested in an adapted prognostic staging system while the results of de-intensified treatment trials are awaited. Carcinogenesis caused by HPV in the mucosal linings of the upper aerodigestive tract remains an enigma, but with some recent observations, a model can be proposed. In 2015, The Cancer Genome Atlas (TCGA) consortium published a comprehensive molecular catalogue on HNSCC. Frequent mutations of novel druggable oncogenes were not demonstrated, but the existence of a subgroup of genetically distinct HPV-negative head and neck tumours with favourable prognoses was confirmed. Tumours can be further subclassified based on genomic profiling. However, the amount of molecular data is currently overwhelming and requires detailed biological interpretation. It also became apparent that HNSCC is a disease characterized by frequent mutations that create neoantigens, indicating that immunotherapies might be effective. In 2016, the first results of immunotherapy trials with immune checkpoint inhibitors were published, and these may be considered as a paradigm shift in head and neck oncology.
802 citations
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University of Birmingham1, Newcastle University2, Weston Park Hospital3, University of Warwick4, Castle Hill Hospital5, Aberdeen Royal Infirmary6, Royal Surrey County Hospital7, Mount Sinai St. Luke's and Mount Sinai Roosevelt8, Cheltenham General Hospital9, Nottingham University Hospitals NHS Trust10, James Cook University Hospital11, Abertawe Bro Morgannwg University Health Board12, United Hospitals13, University Hospital Coventry14, Western General Hospital15, Beatson West of Scotland Cancer Centre16, VU University Amsterdam17, The Royal Marsden NHS Foundation Trust18, University of Oxford19
TL;DR: Cisplatin and radiotherapy should be used as the standard of care for HPV-positive low-risk patients who are able to tolerate cisplatin, and cetuximab showed significant detriment in terms of tumour control.
661 citations
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01 Dec 2016
TL;DR: HPV testing will probably replace cytology-based cervical screening owing to greater reassurance when the test is negative, however, the effective implementation of HPV vaccination and screening globally remains a challenge.
Abstract: Infections with human papillomavirus (HPV) are common and transmitted by direct contact. Although the great majority of infections resolve within 2 years, 13 phylogenetically related, sexually transmitted HPV genotypes, notably HPV16, cause - if not controlled immunologically or by screening - virtually all cervical cancers worldwide, a large fraction of other anogenital cancers and an increasing proportion of oropharyngeal cancers. The carcinogenicity of these HPV types results primarily from the activity of the oncoproteins E6 and E7, which impair growth regulatory pathways. Persistent high-risk HPVs can transition from a productive (virion-producing) to an abortive or transforming infection, after which cancer can result after typically slow accumulation of host genetic mutations. However, which precancerous lesions progress and which do not is unclear; the majority of screening-detected precancers are treated, leading to overtreatment. The discovery of HPV as a carcinogen led to the development of effective preventive vaccines and sensitive HPV DNA and RNA tests. Together, vaccination programmes (the ultimate long-term preventive strategy) and screening using HPV tests could dramatically alter the landscape of HPV-related cancers. HPV testing will probably replace cytology-based cervical screening owing to greater reassurance when the test is negative. However, the effective implementation of HPV vaccination and screening globally remains a challenge.
560 citations