Journal of the National Cancer Institute最新文献

{"title":"Assessing the oncologic risk when systematic and multiparametric magnetic resonance imaging-targeted prostate biopsy grade groups are discordant.","authors":"Simone Scuderi, ,Amy L Tin,Giancarlo Marra,Lorenzo Bianchi,Claudia Kesch,Timo F W Soeterik,Guillaume Ploussard,Fabio Zattoni,Otto Ettala,Andreas Røder,Cédric Poyet,Hein Vincent Stroomberg,Umberto Cimmino,Gaelle Fiard,Tobias Nordström,Hiten D Patel,Gopal N Gupta,Paul M Yonover,Benedicte Guillaume,Cristopher Gaffney,Junlong Zhuang,YanQin Wang,Julien Sarkis,Teddy Jabbour,Romain Diamand,Olivier Windisch,Jonathan Olivier,Ahmad Abbadi,Eric H Kim,Johnny C Wang,Jim Hu,Alec Zhu,Armando Stabile,James A Eastham,Francesco Montorsi,Alberto Briganti,Giorgio Gandaglia, ,Andrew J Vickers","doi":"10.1093/jnci/djaf275","DOIUrl":"https://doi.org/10.1093/jnci/djaf275","url":null,"abstract":"BACKGROUND AND OBJECTIVEIn the systematic biopsy (SBx) era, prostate biopsy grading followed the rule that the ISUP grade group (GG) assigned was the highest GG of any core. This rule has been retained in the era of multiparametric magnetic resonance imaging (MRI)-guided biopsy in the case of discordance between SBx and targeted (TBx) samples. We assessed whether oncologic risk in patients undergoing SBx and TBx was driven by the highest GG of the two.METHODSOverall, 6,588 patients received SBx plus MRI-TBx and radical prostatectomy. We assessed advanced stage (seminal vesicle (SVI) or lymph node invasion (LNI) ± extraprostatic extension (EPE)), adverse pathology (advanced stage or high GG), and biochemical recurrence (BCR) for each SBx and MRI-TBx GG combination.KEY FINDINGS AND LIMITATIONSOverall, 3,405 (52%) had discordant GGs. When SBx and MRI-TBx grades were discordant, the risk of advanced-stage disease was intermediate. For instance, the risk of advanced pathologic stage was 23% for GG3 on both SBx and TBx, and 8.8% for concordant GG2. The risk was 18% for patients with SBx GG3 but TBx GG2, and 15% if the reverse were true. Similar results were seen for other outcomes.CONCLUSIONS AND CLINICAL IMPLICATIONSWhen the GG is discordant between SBx and TBx, the risk is intermediate. The current approach of assigning the highest GG should be abandoned, and urologists should consider de-escalating treatment intensity for patients with discordant SBx and MRI-TBx GGs. Our findings are plausibly explained by pattern 4 volume being the primary driver of risk.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in chemotherapy completion, toxicities, and survival in colon cancer: an analysis of 2201 patients from CALGB/SWOG 80702 (alliance).","authors":"En Cheng,Qian Shi,Anthony F Shields,Xiaonan Xue,Thomas E Rohan,Chaoyuan Kuang,Ardaman P Shergill,Chao Ma,Felix Couture,J Philip Kuebler,Pankaj Kumar,Benjamin Tan,Smitha S Krishnamurthi,Kimmie Ng,Eileen M O'Reilly,Justin C Brown,Jeffrey A Meyerhardt","doi":"10.1093/jnci/djaf281","DOIUrl":"https://doi.org/10.1093/jnci/djaf281","url":null,"abstract":"BACKGROUNDCompleting adjuvant chemotherapy and reducing toxicities are critical tenets to maximize survival after colon cancer diagnosis. Sex, as a biological variable, may impact colon cancer chemotherapy completion, toxicities, and survival differently.METHODSFrom an NCI-sponsored trial conducted among patients with stage III colon cancer (CALGB/SWOG 80702), we included 2201 patients receiving standard adjuvant chemotherapy FOLFOX (fluorouracil, leucovorin, and oxaliplatin). We calculated relative dose intensity (RDI) to indicate chemotherapy completion and considered reduced RDI (RDI <85%) as a clinically significant deviation from standard FOLFOX. Using NCI's Common Terminology Criteria for Adverse Events (AE), we defined severe AE (grade ≥3) as the occurrence of any following event including neutrophils decrease, nausea, platelets decrease, hypertension, peripheral neuropathy, diarrhea, fatigue, gastritis, creatinine increase, gastric ulcer, myocardial ischemia, and cerebral ischemia. The primary survival outcome was disease-free survival (time from enrollment to colon cancer recurrence or death from any cause), and secondary survival outcomes were recurrence-free and overall survival.RESULTSCompared to males, females were at significantly higher risks of experiencing reduced RDI (adjusted OR 1.59 [1.29-1.96]; P < .001) and severe AE (adjusted OR: 1.72 [1.41-2.11]; P < .001). Yet, females had significantly better disease-free survival (adjusted HR: 0.72 [0.59, 0.87]; P < .001) as well as better recurrence-free and overall survival.CONCLUSIONSOur findings suggested that females with colon cancer are more likely to have worse chemotherapy completion and more severe AE, but they have better survival. Sex, as a biological variable, warrants further consideration in chemotherapy administration and survivorship management after colon cancer diagnosis.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer decentralized clinical trials in the veterans health administration.","authors":"Daphne R Friedman,Shannon L Elam,Sarah Bloemers,Zachary Burningham,Jacqueline Boreland,Ashlyn M Press,Jennifer Ordman,Crystal Okeke,Jo Martinez,Tiffany Stewart,Shelby Schoenborn,Perri Pepperman,Holly Morris,Bethany Oberg,Michael J Kelley","doi":"10.1093/jnci/djaf279","DOIUrl":"https://doi.org/10.1093/jnci/djaf279","url":null,"abstract":"BACKGROUNDDespite the importance of clinical trials (CTs) in the advancement of cancer treatments, there are barriers to subject enrollment. Decentralized clinical trials (DCTs) are conducted at a different physical location than where patients receive medical care and can address patient- and institutional-level barriers that impact subject enrollment.METHODSThe Veterans Health Administration (VA) created a cancer DCT program, with a dedicated research team, operational manual, and other standardized operational protocols to support DCT conduct. The DCT program works closely with the VA Office of Research and Development and VA central institutional review board.RESULTSTen cancer DCTs have been implemented two observational, five non-therapeutic interventional, and three therapeutic interventional. Eight were implemented as fully remote DCTs and two were hybrid DCTs, with hybrid requiring collaboration with local clinicians for non-research activities. Across 47 VA Medical Centers, 134 Veterans enrolled: 31 (23%) in observational, 99 (74%) in non-therapeutic interventional, and 4 (3%) in therapeutic interventional DCTs. Demographic characteristics of enrolled subjects mirror that of Veterans receiving cancer care through the VA the National TeleOncology service, including rurality (31%) and non-White minority status (19%). Examples of the methods for research conduct that have been used across these DCTs are included.CONCLUSIONSCancer DCTs can address barriers to subject enrollment, but not every CT is appropriate to be conducted as a DCT. By sharing experiences regarding the conduct of cancer DCTs in the VA, research sponsors, regulatory authorities, and other research groups can more readily and widely implement DCTs.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global paid and unpaid productivity losses due to cancer-related mortality.","authors":"Yek-Ching Kong,Jean Niyigaba,Phuong Bich Tran,Jerome Vignat,Freddie Bray,Cindy L Gauvreau,Paul Hanly,Alison Pearce,Marianna de Camargo Cancela,Marta Ortega-Ortega,Nirmala Bhoo-Pathy,André Ilbawi,Filip Meheus,Isabelle Soerjomataram","doi":"10.1093/jnci/djaf193","DOIUrl":"https://doi.org/10.1093/jnci/djaf193","url":null,"abstract":"BACKGROUNDCancer is among the most important causes of premature deaths globally. We estimated the value of paid and unpaid productivity losses due to premature mortality in 2022 from all cancers worldwide.METHODSYears of productive life lost were derived from cancer mortality data for 36 cancer types among people of working age (15-64 years) in 185 countries for the year 2022. Paid productivity losses were estimated using the human capital approach, while unpaid activities were valued using the opportunity cost approach. Lost productivity was estimated using wages, workforce statistics, and time spent on unpaid activities from various sources. All analyses were performed by sex and age group for each country.RESULTSIn 2022, productivity losses from premature cancer mortality were valued at an estimated US$566 billion, equivalent to 0.6% of the global gross domestic product. Of the total value, 53.9% (US$305 billion) was attributable to paid productivity losses, and 46.1% (US$260 billion) to unpaid productivity losses. Paid productivity losses were generally higher among men, while unpaid productivity losses were greater among women, with variations seen across world regions. The total value of lost productivity was greatest for lung cancer, followed by breast and liver cancers. Per cancer death, testicular cancer, melanoma of the skin, and brain and nervous system cancer generated the highest value of productivity losses.CONCLUSIONThe substantial value of productivity losses from premature cancer mortality highlights its marked societal burden. Continuous investments in global cancer control efforts, including in less common cancers, will yield substantial returns-on-investment to national economies, especially in transitioning countries.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol consumption and upper aerodigestive tract squamous cell carcinoma: evidence from 28 prospective cohorts.","authors":"Elmira Ebrahimi,Sabine Naudin,Niki Dimou,Ana-Lucia Mayén,Molin Wang,Christian C Abnet,Agneta Åkesson,Matthew J Barnett,Rino Bellocco,Amy Berrington de Gonzalez,Stephanie E Bonn,Chu Chen,David C Christiani,Tracy E Crane,A Heather Eliassen,Jo L Freudenheim,Yu-Tang Gao,Montse Garcia-Closas,Gretchen Gierach,Edward L Giovannucci,Inger T Gram,Niclas Håkansson,Mayo Hirabayashi,Tao Hou,Brian Z Huang,José-Maria Huerta,Harindra Jayasekara,Woon-Puay Koh,James V Lacey,Ylva Trolle Lagerros,Erikka Loftfield,Robert J MacInnis,Satu Mannisto,Maria Elena Martinez,Marjorie L McCullough,Roger L Milne,Steven C Moore,Lorelei A Mucci,Marian L Neuhouser,Elizabeth A Platz,Jenny N Poynter,Anna E Prizment,Samantha Rees,Kim Robien,Thomas E Rohan,Norie Sawada,V Wendy Setiawan,Marissa M Shams-White,Xiao-Ou Shu,Rashmi Sinha,Meir J Stampfer,Rachael Z Stolzenberg-Solomon,Cynthia A Thomson,Caroline Y Um,Piet A van den Brandt,Kala Visvanathan,Renwei Wang,Sophia S Wang,Emily White,Kami K White,Walter C Willet,Alicja Wolk,Yukiko Yano,Shiaw-Shyuan Yaun,Jian-Min Yuan,Wei Zheng,Elio Riboli,Stephanie A Smith-Warner,Paul Brennan,Pietro Ferrari","doi":"10.1093/jnci/djaf230","DOIUrl":"https://doi.org/10.1093/jnci/djaf230","url":null,"abstract":"BACKGROUNDThis study aimed to investigate the association between alcohol consumption and squamous cell cancers of the upper aerodigestive tract (UADT), using data from 28 cohorts within the Pooling Project of Prospective Studies of Diet and Cancer (DCPP).METHODSIndividual-level data from 2,365,437 participants were pooled. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models to quantify the association between alcohol consumption (grams/day) and UADT cancers risk, adjusting for potential confounders. Analyses were conducted by sex, smoking status, geographic region, and alcoholic beverages.RESULTSOver a median follow-up of 15.5 years, 6,903 UADT cancer cases were identified. Alcohol consumption was positively associated with UADT cancers risk overall. Even at intakes as low as 5-<15 g/day the HR estimate was 1.12 (95% CI 1.03,1.21) compared with the reference group (0.1-<5 g/day). The HR10g/day (95% CI) was 1.16 (1.14,1.18) for women and 1.12 (1.11,1.13) for men (pheterogeneity<0.0001). HR10g/day estimates were 1.14 (1.13,1.15) in current, 1.10 (1.09,1.12) in former, and 1.15 (1.12,1.18) in never-smokers. Consistent UADT HR10g/day estimates were observed across all beverage types. HR10g/day estimates varied across geographic regions, with HR10g/day (95% CI) equal to 1.15 (1.14,1.17) in Europe-Australia, 1.13 (1.11,1.15) in Asia, and 1.11 (1.09,1.12) in North America (pheterogeneity<0.0001).CONCLUSIONAlcohol consumption was associated with UADT cancer risk, irrespective of smoking status or beverage type. However, due to differential baseline risks, alcohol is expected to impact the UADT cancer burden more in smokers than never-smokers. These findings support public health strategies to reduce alcohol consumption.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"75 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prostate-specific antigen levels at age 60 and lifetime risk of lethal prostate cancer","authors":"Emily A Vertosick, Andrew Vickers, Anders Dahlin, David Ulmert, Sigrid V Carlsson, James Eastham, Anders Bjartell, Hans Lilja","doi":"10.1093/jnci/djaf271","DOIUrl":"https://doi.org/10.1093/jnci/djaf271","url":null,"abstract":"Introduction We investigated the natural history of the relationship between PSA at age 60 and lifetime risk of prostate cancer death in an unscreened cohort followed for 40 years, the Malmö Preventive Project. We also investigated whether percent free PSA could risk-stratify men with low PSAs. Methods The cohort included 1162 men aged 58-62 at blood draw in 1981-82, with 1151 deaths by December 31, 2020. Total and free PSA were measured for 130 men with prostate cancer and 517 without prostate cancer. Lorenz curves were calculated for life years lost to prostate cancer by baseline PSA level. Results Total PSA at age 60 remained highly predictive for full lifetime risk of lethal prostate cancer (C-index 0.87, 95% CI 0.82, 0.92). More than half of the life years lost to prostate cancer in this cohort were in men who had a PSA &amp;gt;4.0 ng/ml (59%, 95% CI 54%, 63%) at age 60, with 85% (95% CI 81%, 89%) and 92% (95% CI 90%, 94%) in men with a PSA &amp;gt;2.0 ng/ml and &amp;gt;1.0 ng/ml respectively. Percent free PSA did not aid risk stratification in men with low PSA. Conclusion Men with a PSA below 1-2 ng/ml at age 60 are at low risk for lethal prostate cancer and do not require further PSA screening. Unlike a proven role in men with elevated PSA, percent free PSA is not useful in informing the decision to stop or continue further PSA screening for men with PSA &amp;lt; 2 ng/ml at age 60.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges in the return of molecular tumor profiling results.","authors":"Heinz-Josef Lenz,David W Craig,Kevin C Johnson,Roel Verhaak,Oindrila Bhattacharyya,Bethany Davis,Cherie Wesley,Sara A Byron,Cheryl Willman,Lindsey Kelley,Elizabeth B Claus,Jeffrey Trent,Julie O Culver,Stacy W Gray,Alanna J Church","doi":"10.1093/jnci/djaf251","DOIUrl":"https://doi.org/10.1093/jnci/djaf251","url":null,"abstract":"Next-generation sequencing (NGS) has transformed cancer care by providing essential insights for diagnosis, prognosis, and treatment. However, variability in testing timing, reporting practices, and interpretation challenges limits its clinical impact. This manuscript highlights key opportunities to optimize somatic reporting, emphasizing the importance of timely testing throughout the cancer care continuum to maximize the diagnostic and therapeutic relevance of findings. Technical factors such as test design, sequencing depth, and the use of liquid biopsy significantly influence result accuracy and interpretation, underscoring the need for careful integration with clinical history. Standardized reporting practices that clearly delineate diagnostic, prognostic, and therapeutic findings can enhance the clinical utility of NGS results. Streamlined formats and curated clinical trial data further support actionable decision-making. Additionally, direct patient engagement and education are essential for empowering patients to navigate genomic testing and make informed decisions about their care. By leveraging multidisciplinary tumor boards, decision-support tools, and emerging AI technologies, clinicians can better navigate the complexities of somatic reports. Standardization and clarity in reporting are critical to advancing precision oncology, empowering providers and patients to make informed treatment decisions and improve outcomes.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gaps in care across the cancer screening continuum for cervical, colorectal and lung cancer.","authors":"Jennifer S Haas,Kaitlin W Todd,Dale Mclerran,Jasmin A Tiro,Anil Vachani,Sarah Kobrin,Chelsea Saia,Celette Sugg Skinner,Yingye Zheng,Jessica Chubak,Douglas A Corley,Robert T Greenlee,Ethan A Halm,Christopher I Li","doi":"10.1093/jnci/djaf248","DOIUrl":"https://doi.org/10.1093/jnci/djaf248","url":null,"abstract":"BACKGROUNDWhile screening for cervical, colorectal, and lung cancers reduce cancer-specific mortality, the full benefits of screening are only realized when coupled with timely care across the subsequent \"screening continuum\" steps, including surveillance (results warranting frequent monitoring), diagnostic evaluation (results that require additional testing), and treatment (detected cancers). Our goal was to describe the proportion of individuals receiving timely cervical, colorectal, and lung cancer care at each step in the screening continuum.METHODSThis retrospective cohort study used data from the 10 health care settings that participate in the Population-based Research to Optimize the Screening Process (PROSPR II) consortium and included individuals who were eligible for a step along the cancer screening continuum in 2018. Proportions of individuals who received timely testing were calculated for screening, surveillance, and diagnostic tests for each of the three cancers and treatment (colorectal only), and the association of these outcomes with patient characteristics was evaluated using multivariate logistic regression.RESULTSThe overall proportions of timely screening, surveillance, and diagnostic testing were 41.8%, 37.3%, and 61.2%, for cervical cancer; 82.4%, 45.5%, and 73.5% for colorectal (94.1% for timely treatment); and 73.8%, 80.5%, and 80.7% for lung cancer. Across all three cancers, there were differences across the screening continuum by insurance status, race/ethnicity, and socioeconomic status.CONCLUSIONSThere are important gaps in care across the screening continuum beyond common metrics for screening uptake. Comparison across organ types may facilitate the identification of interventions and policies that could broadly improve cancer prevention and promote health equity.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating tumor human papillomavirus DNA whole genome sequencing enables human papillomavirus-associated oropharynx cancer early detection.","authors":"Dipon Das,Shun Hirayama,Ling Aye,Michael E Bryan,Saskia Naegele,Brian Zhao,Vasileios Efthymiou,Julia Mendel,Adam S Fisch,Zoe Guan,Lea Kröller,Birgitta E Michels,Tim Waterboer,Jeremy D Richmon,Viktor Adalsteinsson,Michael S Lawrence,Matthew G Crowson,A John Iafrate,Daniel L Faden","doi":"10.1093/jnci/djaf249","DOIUrl":"https://doi.org/10.1093/jnci/djaf249","url":null,"abstract":"PURPOSEEarly detection of HPV-associated oropharyngeal cancer (HPV+OPSCC), the most common HPV cancer in the United States, could reduce disease-related morbidity and mortality, yet currently, there are no early detection tests. Circulating tumor HPV DNA (ctHPVDNA) is a sensitive and specific biomarker for HPV+OPSCC at diagnosis. It is unknown if ctHPVDNA is detectable prior to diagnosis, and thus it's potential as an early detection test.METHODSPlasma samples from the MassGeneralBrigham biobank collected 1.3-10.8 years prior to diagnosis from HPV+OPSCC patients (n = 28) and age- and sex-matched controls (n = 28) were blinded and run on a newly developed and validated multi-feature HPV whole genome sequencing liquid biopsy assay and a validated HPV antibody assay.RESULTSctHPVDNA results were positive in 22/28 pre-diagnostic samples from HPV+OPSCC cases (sensitivity 79%) with a maximum lead time of 7.8 years. ctHPVDNA results were negative in all controls (0/28 controls, 100% specificity). Diagnostic accuracy was highest within four years of cancer diagnosis and was higher than HPV Ab detection within the same time frame (p-value 0.004). Application of a machine learning model trained and tested on an independent cohort of 306 cases and controls increased the sensitivity of detection to 27/28 cases (overall sensitivity 96%) and the maximum lead time to 10.3 years.CONCLUSIONSCirculating tumor HPV DNA can be detected in the blood years prior to diagnosis with HPV+OPSCC, with high specificity, in a case-control cohort of 56 participants. ctHPVDNA detection alone, or in combination with previously identified serological biomarkers may be a feasible approach to early detection of HPV+OPSCC.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germline rare variants in cancer susceptibility genes and subsequent neoplasm risk after childhood cancer.","authors":"Shahriar A Zamani,Danielle M Karyadi,Stephen W Hartley,Todd M Gibson,Joshua N Sampson,Peter Kraft,Stephen J Chanock,Lindsay M Morton","doi":"10.1093/jnci/djaf260","DOIUrl":"https://doi.org/10.1093/jnci/djaf260","url":null,"abstract":"BACKGROUNDAmong childhood cancer survivors, germline rare variants in autosomal dominant cancer susceptibility genes (AD CSGs) could increase subsequent neoplasm (SNs) risks, but risks for rarer SNs and by age at onset are not well understood.METHODSWe pooled the Childhood Cancer Survivor Study and St Jude Lifetime Cohort (median follow-up = 29.7 years, range 7.1-55.6) to identify rare deleterious germline variants across 150 literature-based CSGs using ClinVar and SnpEff. Conditional logistic regression evaluated overall and SN-specific risk, matching up to 100 SN-free controls to cases by age, sex, childhood cancer, radiation dose, chemotherapy, study, and follow-up time.RESULTSAmong 11,840 survivors, 2,165 (18.3%) developed ≥1 SN. Overall SN risk was modestly increased for variant carriers in any AD CSG (cases = 288/2165, 13.3%, controls = 9.9%; odds ratio, 95% confidence interval: 1.4, 1.3 to 1.6, p = 5.0 × 10-7). Carriers of variants in cancer-specific AD CSGs had higher SN risks, particularly for glioma (20.4, 7.4 to 56.1, p = 2.7 × 10-10), colorectal cancer (5.9, 1.4 to 25.7, p = 9.1 × 10-3), bone/soft-tissue sarcoma (5.3, 2.2 to 12.7, p = 1.5 × 10-3), meningioma (4.0, 1.4 to 1.0, p = 3.2 × 10-3), basal cell carcinoma (3.5, 1.2 to 10.0, p = .020), and breast cancer (2.6, 1.8 to 3.9, p = 2.8 × 10-6), who were also more likely to develop such SNs at younger ages. Notably, all meningioma, sarcoma, and glioma SNs among carriers occurred before ages 20, 25, and 35 years, respectively.CONCLUSIONSSurvivors with rare germline variants in cancer-specific AD CSGs had increased SN risk, especially at younger ages. These findings offer a potential basis for enhancing risk-stratified long-term surveillance for childhood cancer survivors.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"67 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}