Author
Laia Alemany
Other affiliations: University of Barcelona, Bellvitge University Hospital
Bio: Laia Alemany is an academic researcher from Carlos III Health Institute. The author has contributed to research in topics: Cervical cancer & Cancer. The author has an hindex of 33, co-authored 111 publications receiving 6900 citations. Previous affiliations of Laia Alemany include University of Barcelona & Bellvitge University Hospital.
Topics: Cervical cancer, Cancer, HPV vaccines, Medicine, HPV infection
Papers
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Instituto Português de Oncologia Francisco Gentil1, National Autonomous University of Mexico2, University of Valencia3, National Cheng Kung University4, University of Buenos Aires5, Universidad Nacional de Asunción6, Makerere University7, University of Chile8, American University of Beirut9, Hacettepe University10, Hospital General San Juan de Dios11, Lagos University Teaching Hospital12, University of Barcelona13, University of the Philippines14, Bangabandhu Sheikh Mujib Medical University15, Prince of Songkla University16, Peking Union Medical College17, Royal Women's Hospital18, Kanazawa University19, Charles University in Prague20, Harvard University21, VU University Amsterdam22, Kuwait University23, Columbia University Medical Center24, University of Crete25, Aristotle University of Thessaloniki26, Central University of Venezuela27, University of Las Palmas de Gran Canaria28, University of Antioquia29, Medical University of Lublin30, Western Galilee Hospital31
TL;DR: HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines, according to this largest assessment of HPV genotypes to date.
Abstract: Summary Background Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer. Methods Paraffin-embedded samples of histologically confirmed cases of invasive cervical cancer were collected from 38 countries in Europe, North America, central South America, Africa, Asia, and Oceania. Inclusion criteria were a pathological confirmation of a primary invasive cervical cancer of epithelial origin in the tissue sample selected for analysis of HPV DNA, and information about the year of diagnosis. HPV detection was done by use of PCR with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridisation line probe assay. Sequence analysis was done to characterise HPV-positive samples with unknown HPV types. Data analyses included algorithms of multiple infections to estimate type-specific relative contributions. Findings 22 661 paraffin-embedded samples were obtained from 14 249 women. 10 575 cases of invasive cervical cancer were included in the study, and 8977 (85%) of these were positive for HPV DNA. The most common HPV types were 16, 18, 31, 33, 35, 45, 52, and 58 with a combined worldwide relative contribution of 8196 of 8977 (91%, 95% CI 90–92). HPV types 16 and 18 were detected in 6357 of 8977 of cases (71%, 70–72) of invasive cervical cancer. HPV types 16, 18, and 45 were detected in 443 of 470 cases (94%, 92–96) of cervical adenocarcinomas. Unknown HPV types that were identified with sequence analysis were 26, 30, 61, 67, 69, 82, and 91 in 103 (1%) of 8977 cases of invasive cervical cancer. Women with invasive cervical cancers related to HPV types 16, 18, or 45 presented at a younger mean age than did those with other HPV types (50·0 years [49·6–50·4], 48·2 years [47·3–49·2], 46·8 years [46·6–48·1], and 55·5 years [54·9–56·1], respectively). Interpretation To our knowledge, this study is the largest assessment of HPV genotypes to date. HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines. Our results also suggest that type-specific high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45. Funding Spanish grants from Instituto de Salud Carlos III, Agencia de Gestio d'Ajuts Universitaris i de Recerca, Marato de TV3 Foundation, and unrestricted grants from GlaxoSmithKline Biologicals, Sanofi Pasteur MSD, and Merck.
2,145 citations
TL;DR: The contribution of HPV prevalence in head and neck squamous cell carcinoma and in particular that of HPV16 in the oropharynx shows the potential benefit of prophylactic vaccines.
Abstract: Summary Background We aimed to provide updated information about the global estimates of attributable fraction and type distribution of human papillomavirus (HPV) in head and neck squamous cell carcinomas by doing a systematic review and meta-analysis. Methods We did a literature search on PubMed to identify studies that used PCR for detection of HPV DNA in head and neck squamous cell carcinomas with information about HPV genotype distribution. We included studies that tested 20 or more biopsies per cancer site and were published between July 15, 1990, and Feb 29, 2012. We collected information about sex, risk factors, HPV detection methods, and biomarkers of potentially HPV-induced carcinogenesis (E6/E7 mRNA and p16 INK4a ). If it was not possible to abstract the required information directly from the paper, we contacted the authors. We did a meta-analysis to produce pooled prevalence estimates including a meta-regression to explore sources of heterogeneity. Findings 148 studies were included, contributing data for 12 163 cases of head and neck squamous cell carcinoma from 44 countries. HPV DNA was detected in 3837 cases. HPV16 accounted for 82·2% (95% CI 77·7–86·4) of all HPV DNA positive cases. By cancer site, pooled HPV DNA prevalence estimates were 45·8% (95% CI 38·9–52·9) for oropharynx, 22·1% (16·4–28·3) for larynx (including hypopharynx), and 24·2% (18·7–30·2) for oral cavity. The percent positivity of p16 INK4a positive cases in HPV-positive oropharyngeal cancer cases was 86·7% (95% CI 79·2–92·9) and of E6/E7 mRNA positive cases was 86·9% (73·2–96·8). The estimate of HPV attributable fraction in oropharyngeal cancer defined by expression of positive cases of E6/E7 mRNA was 39·8% and of p16 INK4a was 39·7%. Of subsites, tonsils (53·9%, 95% CI 46·4–61·3) had the highest HPV DNA prevalence. HPV DNA prevalence varied significantly by anatomical site, geographic region, but not by sex or tobacco or alcohol consumption. Interpretation The contribution of HPV prevalence in head and neck squamous cell carcinoma and in particular that of HPV16 in the oropharynx shows the potential benefit of prophylactic vaccines. Funding European Commission.
574 citations
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
University of Alabama1, International Agency for Research on Cancer2, University of California, San Francisco3, Ohio State University4, Medical Research Council5, University of Manchester6, University of Cambridge7, University of Antwerp8, University of Ljubljana9, Queen Mary University of London10, National Institutes of Health11, Centers for Disease Control and Prevention12, University of Western Ontario13, University of New South Wales14, University of Cape Town15, McGill University16, VU University Amsterdam17, Harvard University18
TL;DR: There must be ongoing efforts including international advocacy to achieve widespread-optimally universal-implementation of HPV prevention strategies in both developed and developing countries.
352 citations
University of Barcelona1, Middlemore Hospital2, Medical University of Vienna3, Charles University in Prague4, Westmead Hospital5, Instituto Português de Oncologia Francisco Gentil6, Hacettepe University7, American University of Beirut8, Medical University of Lublin9, Manchester Royal Infirmary10, French Institute of Health and Medical Research11, University of Düsseldorf12, Universidad Nacional de Asunción13, Hospital General San Juan de Dios14, Mexican Social Security Institute15, Hospital Italiano de Buenos Aires16, All India Institute of Medical Sciences17, Aristotle University of Thessaloniki18, University of Iowa19, University of Hawaii20, Gomel State Medical University21, Jagiellonian University Medical College22, University of Chile23, Western Galilee Hospital24, Universidad Nacional Autónoma de Honduras25, National Cheng Kung University26, Lagos University Teaching Hospital27
TL;DR: Combined data from HPV-DNA and p16(INK4a) testing are likely to represent a closer estimate of the real fraction of IVC induced by HPV, indicating that HPV contribution in invasive vulvar cancer has probably been overestimated.
320 citations
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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
TL;DR: Applied cancer control measures are needed to reduce rates in HICs and arrest the growing burden in LMICs, as well as for lung, colorectal, breast, and prostate cancer, although some low- and middle-income countries (LMIC) now count among those with the highest rates.
Abstract: There are limited published data on recent cancer incidence and mortality trends worldwide. We used the International Agency for Research on Cancer's CANCERMondial clearinghouse to present age-standardized cancer incidence and death rates for 2003-2007. We also present trends in incidence through 2007 and mortality through 2012 for select countries from five continents. High-income countries (HIC) continue to have the highest incidence rates for all sites, as well as for lung, colorectal, breast, and prostate cancer, although some low- and middle-income countries (LMIC) now count among those with the highest rates. Mortality rates from these cancers are declining in many HICs while they are increasing in LMICs. LMICs have the highest rates of stomach, liver, esophageal, and cervical cancer. Although rates remain high in HICs, they are plateauing or decreasing for the most common cancers due to decreases in known risk factors, screening and early detection, and improved treatment (mortality only). In contrast, rates in several LMICs are increasing for these cancers due to increases in smoking, excess body weight, and physical inactivity. LMICs also have a disproportionate burden of infection-related cancers. Applied cancer control measures are needed to reduce rates in HICs and arrest the growing burden in LMICs.
2,742 citations
TL;DR: This review summarizes the most significant differences between the newly published classification of urogenital tumours and the prior version for renal, penile, and testicular tumours.
2,024 citations
TL;DR: The global scale-up of HPV vaccination and HPV-based screening—including self-sampling—has potential to make cervical cancer a rare disease in the decades to come, and could help shape and monitor the initiative to eliminate cervical cancer as a major public health problem.
1,867 citations
American Cancer Society1, National Institutes of Health2, Emory University3, Memorial Sloan Kettering Cancer Center4, University of Minnesota5, University of Massachusetts Medical School6, University of Arizona7, University of New Mexico8, Harvard University9, Cornell University10, University of California, San Francisco11, McGill University12, University of Virginia13, American Society for Clinical Pathology14, Duke University15
TL;DR: An update to the ACS guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented, addressing age‐appropriate screening strategies, including the use of cytology and high‐risk human papillomavirus (HPV) testing.
Abstract: An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from 6 working groups, and a recent symposium cosponsored by the ACS, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology, which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (eg, the management of screen positives and screening intervals for screen negatives) of women after screening, the age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections.
1,621 citations