Int J Cancer
· 2026 Jun · PMID 42290019
·
Publisher ↗
The Oncotype DX assay has revolutionized the management of early-stage, hormone receptor-positive, HER2-negative breast cancer. Developed in 2004, it quantifies 21 genes to generate a recurrence score that predicts dista...The Oncotype DX assay has revolutionized the management of early-stage, hormone receptor-positive, HER2-negative breast cancer. Developed in 2004, it quantifies 21 genes to generate a recurrence score that predicts distant recurrence risk and guides adjuvant chemotherapy. Multiple studies have validated its reliability and clinical utility in enabling more precise risk stratification and individualized treatment planning, thereby minimizing unnecessary chemotherapy exposure and improving patient outcomes. Leading oncology organizations such as the American Society of Clinical Oncology and National Comprehensive Cancer Network have incorporated it into their clinical guidelines. Beyond its well-established role in adjuvant chemotherapy decision-making, Oncotype DX is increasingly being investigated in broader clinical contexts, including lymph node-positive breast cancer, neoadjuvant therapy, radiotherapy, and ductal carcinoma in situ. Ongoing research and technological advancements, such as artificial intelligence-based predictive models and novel biomarker identification, hold significant promise for further enhancing its predictive accuracy and expanding its applications. This review synthesizes current evidence supporting the clinical utility of Oncotype DX, discusses evolving applications, and highlights future directions for integrating this genomic tool into precision oncology practice.
Buckley KH, Zhu Y, Dinh K
… +10 more, Hausler R, Gala R, Spiegel SR, Delgado R, Clay DG, Kelly GM, Brower J, Domchek SM, Maxwell KN, Katona BW
Int J Cancer
· 2026 Jun · PMID 42286806
·
Publisher ↗
Recent evidence suggests that carriers of a pathogenic germline variant (PGV) in BRCA1 or BRCA2 may have an increased risk of gastric cancer (GC). However, the specific mechanisms underlying gastric carcinogenesis remain...Recent evidence suggests that carriers of a pathogenic germline variant (PGV) in BRCA1 or BRCA2 may have an increased risk of gastric cancer (GC). However, the specific mechanisms underlying gastric carcinogenesis remain uncertain. Strikingly, recent data have demonstrated that Japanese BRCA1 and BRCA2 PGV carriers with Helicobacter pylori (Hp) exposure have a substantially increased risk of GC compared to non-carriers with Hp exposure, indicating that Hp may be an important risk factor for BRCA1 and BRCA2-associated GC. However, rates of Hp exposure amongst broader BRCA1 and BRCA2 PGV cohorts are currently unknown. In this study, 1034 United States-based BRCA1 and BRCA2 PGV carriers along with 293 PALB2, ATM, and TP53 PGV carriers were assessed for Hp exposure by assessing Hp IgG positivity in plasma samples. The combined rate of Hp exposure in BRCA1 and BRCA2 carriers was 17.4%. Individually, BRCA1 and BRCA2 carriers had an exposure rate of 16.4% and 18.2%, respectively. Similarly, PALB2, ATM, and TP53 carriers had a combined Hp exposure rate of 18.4%. Among all groups, non-White race was significantly associated with Hp exposure. Approximately 1 in 6 BRCA1, BRCA2, and other DNA repair-related gene PGV carriers had Hp exposure. Future studies are needed to determine the impact of Hp exposure versus active Hp infection on GC risk in these high-risk individuals.
Zhao J, Li K, Zhang Y
… +8 more, Chen Y, Xu L, Hu M, Wang Y, Liu Y, Li X, Wan Z, Lu J
Int J Cancer
· 2026 Jun · PMID 42277929
·
Publisher ↗
HIV-induced immune suppression and chronic inflammation elevate the risk of cancer progression. We conducted a systematic review and meta-analysis of studies published between January 1, 1984 and October 13, 2023 to asse...HIV-induced immune suppression and chronic inflammation elevate the risk of cancer progression. We conducted a systematic review and meta-analysis of studies published between January 1, 1984 and October 13, 2023 to assess the association between HIV infection and liver cancer. People living with HIV (PLHIV) had a higher risk (pooled relative risk = 3.36, 95% CI: 2.72-4.15). The global PAF for HIV-attributed liver cancer was 1.43% in 2019, with a three-fold increase over the past 30 years. The Asia-Pacific region recorded the second highest new cases of HIV-attributed liver cancer in 2019, and the highest age-standardized incidence rate (ASIR) in Eastern and Southern Africa. Particularly, the ASIR of HIV-attributed liver cancer increased rapidly in Eastern Europe and Central Asia, with the highest estimated annual percentage change reaching 22.98%. PLHIV have an increased risk and incidence of liver cancer. In regions with high burden of HIV-attributed liver cancer, it is essential to integrate prevention and effective treatment for HIV, viral hepatitis, alcoholic liver disease, nonalcoholic steatohepatitis, and liver cancer.
Zhong X, Jin X, Cheng Y
… +8 more, Chao X, Kong L, Wang J, Liu P, Liou Y, Xin D, Lang J, Li L
Int J Cancer
· 2026 Jun · PMID 42277588
·
Publisher ↗
Type I to III cervical transformation zones (TZ-1 to TZ-3) may have various effects on cervical cancer screening and diagnostic outcomes. This study aims to evaluate the clinical utility of the cytological PAX1/JAM3 meth...Type I to III cervical transformation zones (TZ-1 to TZ-3) may have various effects on cervical cancer screening and diagnostic outcomes. This study aims to evaluate the clinical utility of the cytological PAX1/JAM3 methylation (CISCER) assay in cervical cancer screening, especially in TZ-3 women. Between November 2020 and October 2022, 1782 women referred for colposcopy underwent liquid-based cytology (LBC), high-risk human papillomavirus (hrHPV) genotyping, and CISCER testing. After applying inclusion criteria, 1398 women were analyzed, including 1190 with documented TZ classification. Diagnostic performance for detecting cervical intraepithelial neoplasia grade 3 or worse (CIN3+) was compared across TZ subgroups. For CIN3+ detection, CISCER showed sensitivities of 67.4%, 72.0%, 48.3%, and 81.5% and specificities of 91.0%, 94.2%, 91.3%, and 89.8% in all women, TZ-1, TZ-2, and TZ-3, respectively. Compared with LBC ≥ ASC-US, hrHPV positivity, or HPV16/18 positivity, CISCER achieved the highest diagnostic accuracy, with AUC values of 0.792, 0.831, 0.698, and 0.856 across the respective groups. In both the overall cohort and TZ-3 subgroup, CISCER positivity was associated with the highest CIN3+ risk (34.6% and 31.4%) and required the fewest colposcopy referrals per CIN3+ detected (2.9 and 3.2). Combining hrHPV testing with CISCER further improved risk stratification. CISCER demonstrated superior diagnostic performance across TZ types, particularly in TZ-3, enabling improved CIN3+ risk discrimination while substantially reducing unnecessary colposcopy referrals compared with conventional cytology and HPV genotyping.
Moiseenko F, Stroyakovskiy D, Levchenko E
… +29 more, Fedyanin M, Gabina A, Oganesian A, Belukhin S, Stepanova M, Stepanova E, Artemyeva E, Myslik A, Volkov N, Bogdanov A, Shuginova T, Kryukov K, Kheinshtein V, Allakhverdiev A, Zaberegniy I, Akhmadiyarova Y, Popov M, Danilova A, Sehniaidze D, Savelov N, Levchenko N, Slugin E, Lopushanskaya O, Kuligina E, Aleksakhina S, Iyevleva A, Ivantsov A, Moiseyenko V, Imyanitov E
Int J Cancer
· 2026 Jun · PMID 42276818
·
Publisher ↗
Non-small cell lung cancer (NSCLC) patients with EGFR mutations usually receive continuous treatment with tyrosine kinase inhibitors (TKIs) until disease progression. We evaluated whether surgical excision of residual tu...Non-small cell lung cancer (NSCLC) patients with EGFR mutations usually receive continuous treatment with tyrosine kinase inhibitors (TKIs) until disease progression. We evaluated whether surgical excision of residual tumor masses offers a survival advantage when performed before progression on TKI therapy. We conducted a retrospective analysis of 230 patients with locally advanced or metastatic EGFR-mutated NSCLC who were treated with first-line EGFR TKI. Among these subjects, surgical intervention appeared technically feasible in 57 patients, 41 of whom underwent cytoreductive surgery while 16 were not operated for various reasons. Both surgically treated and nonsurgically treated patients received TKI until disease progression. The median duration of TKI treatment before surgery was 7.3 months. There was no perioperative mortality, while 8/41 (19.5%) patients experienced surgery-related complications. The median progression-free survival (PFS) and overall survival (OS) in the surgically treated group were 28.4 months and 46.9 months, respectively. These outcomes were significantly better than in patients with potentially resectable disease who did not undergo surgery (PFS: 15.4 months, p = 0.010; OS: 26.5 months, p = 0.015), or in subjects not amenable to cytoreduction (PFS: 19.0 months, p = 0.006; OS: 31.7 months, p = 0.001). Mutation analysis of residual tumor tissues revealed emerging TKI-resistant clones in 4 of 21 investigated patients. At the time of data cut-off, 12/41 (29%) surgically treated patients remained disease-free. In conclusion, surgical removal of residual tumor masses in EGFR-mutated NSCLC during response to TKI may confer a survival advantage.
Chen J, Cui Y, Yuan D
… +6 more, Xiong S, Zhang M, Cao Y, Li S, Duan H, Yang B
Int J Cancer
· 2026 Jun · PMID 42274147
·
Publisher ↗
Bioactive titanium metals with titania/titanate surface were prepared with anodic oxidation, alkali heat, or acid-base treatment methods. It was found that the bioactive Ti could be initiated with a photodynamic effect b...Bioactive titanium metals with titania/titanate surface were prepared with anodic oxidation, alkali heat, or acid-base treatment methods. It was found that the bioactive Ti could be initiated with a photodynamic effect by X-ray used for bone tumor treatment, which could produce a large amount of reactive oxygen species (ROS). This effect could affect the ROS balance of bone tumor cells, cause oxidative stress in the bone tumor cells, and promote apoptosis of bone tumor cells. In the animal test, it was found that the photodynamic therapy (PDT) of the bioactive Ti metal could inhibit bone tumor growth, which implies that the bioactive Ti metal could be endowed with anti-tumor properties during the X-ray therapeutic process. It is hopeful to get Ti metal with synergistic bio-functions with both bioactivity and anti-tumor properties by surface modification.
Zhang D, Xie Q, Zhang Z
… +22 more, Wang S, Liu J, An X, Liu K, Yu Z, Xiang H, He Q, Zheng X, Chang Z, Du R, Zhang L, Li G, Xu Q, Song W, Jin B, Liu C, Li J, Zhou X, Li W, Yang X, Zhang C, Zeng H
Int J Cancer
· 2026 Jun · PMID 42272432
·
Publisher ↗
Icaritin's efficacy was evaluated for unresectable advanced hepatocellular carcinoma (HCC), a major global burden with limited advanced-stage treatment options. A multicenter retrospective real-world study (May 2022-May...Icaritin's efficacy was evaluated for unresectable advanced hepatocellular carcinoma (HCC), a major global burden with limited advanced-stage treatment options. A multicenter retrospective real-world study (May 2022-May 2024) included 163 patients with unresectable advanced HCC. Treatments were Icaritin monotherapy, Icaritin + anti-VEGF, or Icaritin + PD-1 inhibitors + anti-VEGF. Primary endpoints were progression-free survival (PFS) and overall survival (OS); secondary endpoints were objective response rate (ORR) and disease control rate (DCR). Subgroup analyses assessed alpha-fetoprotein (AFP) impact. In first-line treatment, Icaritin monotherapy achieved an ORR of 26.32%. Combining Icaritin with PD-1 inhibitors and anti-VEGF agents increased ORR to 38.30%. Median PFS was 4.27 months for monotherapy; second-line median OS for Icaritin monotherapy reached 19.91 months. Patients with AFP < 400 ng/mL generally showed numerically better PFS in first-line regimens compared to those with AFP ≥ 400 ng/mL. Patients with high AFP treated with Icaritin + PD-1 inhibitors demonstrated a promising response. Icaritin shows promising efficacy in unresectable HCC, particularly in patients with lower AFP levels. The findings support personalized treatment strategies and warrant further research to optimize outcomes and elucidate Icaritin's mechanisms.
Hacan BA, Sonugür FG, Öçal M
… +7 more, Babahan C, Abgarmi S, Arslan ÜY, Şendur MA, Demirkazık A, Utkan G, Akbulut H
Int J Cancer
· 2026 Jun · PMID 42272324
·
Publisher ↗
Efforts to improve outcomes for patients with metastatic colorectal cancer (mCRC) treated with bevacizumab are limited by the lack of validated predictive biomarkers. To overcome this challenge, our study prospectively a...Efforts to improve outcomes for patients with metastatic colorectal cancer (mCRC) treated with bevacizumab are limited by the lack of validated predictive biomarkers. To overcome this challenge, our study prospectively assessed the combined prognostic and predictive significance of circulating angiogenic biomarkers and T-cell subsets. Eighty-eight patients with unresectable mCRC were prospectively enrolled. Pre-treatment serum levels of VEGF, bFGF, PDGF-B, and endothelin-1 (ET-1) were measured by ELISA, nitric oxide by colorimetric assay, and T-cell subsets by flow cytometry. Bevacizumab trough levels and anti-bevacizumab antibodies were assessed by ELISA. Higher baseline levels of proangiogenic factors, including VEGF, PDGF-B, and ET-1, were associated with improved survival. Based on these findings, we developed a novel Angiogenesis Index (AI) using the cut-off values for VEGF, PDGF-B, and ET-1. This AI was a significant predictor of efficacy for bevacizumab-based therapy for both PFS and OS. Furthermore, bevacizumab trough levels exceeding 25 μg/mL on day 14 were associated with improved OS. Likewise, patients with lower baseline circulating FoxP3+ regulatory T cells (Treg) tended to have improved survival. The AI, bevacizumab trough levels, and baseline Treg levels are promising biomarkers for predicting efficacy and refining patient selection for bevacizumab therapy in mCRC.
Int J Cancer
· 2026 Jun · PMID 42267579
·
Publisher ↗
L. R. Santiago, E. Ladoukakis, D. Scibior-Bentkowska, and B. Nedjai, "Polygenic Risk Score and Prostate Specific Antigen Predict Death From Prostate Cancer in Men With Intermediate Aggressive Cancer," International Journ...L. R. Santiago, E. Ladoukakis, D. Scibior-Bentkowska, and B. Nedjai, "Polygenic Risk Score and Prostate Specific Antigen Predict Death From Prostate Cancer in Men With Intermediate Aggressive Cancer," International Journal of Cancer (Early View): 10.1002/ijc.70163. The above article, published online on 16 September 2025 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editor-in-Chief, Christoph Plass; the Union for International Cancer Control; and John Wiley & Sons Ltd. The retraction was agreed upon following the authors' communication to the journal that methodological errors had been identified after publication that were found to have altered outcomes regarding statistical significance and reproducibility of the results presented. Accordingly, the article has been retracted.
Gambron M, Peruzzi E, Perfler S
… +10 more, Montico M, Cecchin R, De Mattia E, Spina M, Lisanti C, Corsetti S, Foltran L, Puglisi F, Roncato R, Cecchin E
Int J Cancer
· 2026 Jun · PMID 42266018
·
Publisher ↗
DPYD and UGT1A1 variants significantly affect fluoropyrimidines and irinotecan safety. While genotype-driven dosing reduces severe toxicity, the impact of individual variants remains incompletely investigated. This retro...DPYD and UGT1A1 variants significantly affect fluoropyrimidines and irinotecan safety. While genotype-driven dosing reduces severe toxicity, the impact of individual variants remains incompletely investigated. This retrospective cohort study includes 178 cancer patients with a matched actionable DPYD and/or UGT1A1 genotypes, defined by the presence of guideline-recommended variants (DPYD: rs3918290, DPYD*2A, c.1905+1G>A; rs55886062, DPYD*13, c.1679T>G; rs67376798, c.2846A>T; rs56038477, c.1236G>A (HapB3); UGT1A1: rs8175347, UGT1A1*28/*37 and rs4148323, UGT1A1*6, c.211G>A), and treated with fluoropyrimidines and/or irinotecan. Patients were classified into standard-of-care (posttreatment genotyping; n = 97) or genotype-driven group (pretreatment genotyping with DPWG-driven dosing; n = 81). Clinically relevant toxicity and relative dose intensity (RDI), a proxy for drug exposure, were evaluated by genotype. Genotype-driven dosing significantly reduced overall clinically relevant toxicity (16.0% vs. 43.3%; p < 0.001). Among DPYD c.1905+1G>A heterozygous carriers, clinically relevant toxicities occurred only within standard-of-care (61.5% vs. 0%, p = 0.007), with lower RDI despite full starting dose (41% [IQR 13-62] vs. 48% [IQR 46-50], p = 0.425). In DPYD c.2846A>T heterozygous carriers, standard-of-care had slightly higher RDI (63% [IQR 54-80] vs. 50% [IQR 43-50], p = 0.007) but doubled toxicity rate (27% vs. 67%, p = 0.092). Conversely, DPYD c.1236G>A (HapB3) heterozygous carriers experienced similarly low toxicity rates (23.7 vs. 13.2, p = 0.375), but genotype-driven dosing markedly reduced RDI (50% [IQR 43-55] vs. 82% [IQR 63-92], p < 0.001). In UGT1A1*28 homozygous carriers, genotype-driven dosing reduced toxicity (21.1% vs. 45.7%, p = 0.086) while preserving comparable RDI (58% [IQR 50-69] vs. 61% [IQR 41-76], p = 0.906). These findings suggest uniform genotype-based strategies may not fully capture variant-specific effects, particularly for DPYD c.1236G>A (HapB3), supporting more flexible dosing approaches.
Hille J, Lorenzen S, Pauligk C
… +15 more, Gensch V, Thuss-Patience P, Goekkurt E, Ettrich T, Lordick F, Bokemeyer C, Müller C, Reichardt P, Sökler M, Pink D, Probst S, Goetze TO, Al-Batran SE, Loges S, Janning M
Int J Cancer
· 2026 Jun · PMID 42266015
·
Publisher ↗
Antiangiogenic treatment with ramucirumab (RAM) is a standard second-line option in advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma. However, reliable biomarkers are lacking. The phase II RAMIRIS tria...Antiangiogenic treatment with ramucirumab (RAM) is a standard second-line option in advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma. However, reliable biomarkers are lacking. The phase II RAMIRIS trial compared RAM plus paclitaxel with RAM plus FOLFIRI (5-fluororuracil, leucovorin and irinotecan) in this setting. We present the exploratory biomarker analysis evaluating placental growth factor (PlGF), carbonic anhydrase IX (CAIX), and tryptase. Plasma samples from 99 patients enrolled in RAMIRIS were collected at predefined timepoints (baseline, Cycle 2 Day 1, and Cycle 4 Day 1). PlGF, CAIX, and tryptase were quantified by ELISA. Associations with progression-free survival (PFS) and overall survival (OS) were analyzed using dichotomized biomarker levels and Cox regression models. PlGF levels increased substantially under treatment, whereas CAIX showed a transient rise, followed by a slight decline, and tryptase remained stable. Elevated PlGF levels at baseline and early-treatment (c2d1) were associated with shorter OS in univariate analysis (baseline HR = 1.75; p = 0.020; c2d1 HR = 1.69; p = 0.054). After multivariate adjustment, the association remained directionally consistent; although statistical support was retained only for c2d1 (baseline HR = 1.41, p = 0.198; c2d1 HR = 1.85, p = 0.030). CAIX and tryptase showed no consistent associations with survival. Elevated PlGF-particularly its early increase during RAM-based therapy-was associated with shortened survival and may represent a dynamic marker of unfavorable prognosis in advanced gastric/GEJ adenocarcinoma. Given the exploratory nature of this analysis, these findings should be considered hypothesis-generating and require validation in independent biomarker-driven studies.
Zhang X, Wang H, Tang W
… +8 more, Kang K, Onyshchenko K, Huang T, Liu D, Xue J, Lu Y, Niedermann G, Luo R
Int J Cancer
· 2026 Jun · PMID 42261253
·
Publisher ↗
Clinical trials combining radiotherapy (RT) with immune checkpoint blockade (ICB) have shown improved outcomes in only a fraction of patients, and optimal strategies for integrating these modalities remain under intense...Clinical trials combining radiotherapy (RT) with immune checkpoint blockade (ICB) have shown improved outcomes in only a fraction of patients, and optimal strategies for integrating these modalities remain under intense investigation. With a few exceptions, phase III combination trials have yielded disappointing results. This may be due to detrimental effects of RT on the tumor-regional immune microenvironment (TRIME), including tumor-draining lymph nodes (TDLNs) and intratumoral immune aggregates such as tertiary lymphoid structures. TDLNs are crucial for generating tumor-specific T cells, including progenitors of exhausted T cells. Intratumoral immune aggregates are hubs for immune cell interaction participating in induction or reactivation of antitumor immune responses. Understanding the biological role of the TRIME in RT/ICB-induced antitumor immunity is therefore essential for designing RT-immunotherapy combination trials. This review also highlights several potential strategies to optimize RT/ICB combination therapy. One approach involves modifying treatment schedules, for example, delaying RT to TDLNs until after ICB to allow effective immune priming. Another promising strategy is the integration of advanced imaging techniques into RT planning to improve precision and minimize radiation exposure to TDLNs. Applying unconventional RT with lower total dose or to selective areas may help preserve immune aggregates within tumors, potentially enhancing synergy with ICB. Another important approach is the use of dendritic cell agonists to boost the function of the TRIME. These approaches may help unlock the full therapeutic potential of RT/ICB combinations.
Brierley JD, Van Eycken LJ, Giuliani ME
… +6 more, Rous BA, Huang SH, Asamura H, Gospodarowicz MK, Lee AW, O'Sullivan B
Int J Cancer
· 2026 Jun · PMID 42261202
·
Publisher ↗
The standard for assessing and recording the extent of the tumour, a necessity for most malignancies, is the Tumour Node Metastases (TNM) classification. The Union for International Cancer Control (UICC) TNM committee ha...The standard for assessing and recording the extent of the tumour, a necessity for most malignancies, is the Tumour Node Metastases (TNM) classification. The Union for International Cancer Control (UICC) TNM committee has defined this since the early 1950s. Due to the expanding medical knowledge of tumour behaviour and advances in imaging, pathology and therapeutic options, TNM has been updated in collaboration with the American Joint Committee on Cancer (AJCC), the International Association for the study of Lung Cancer (IASLC) and the Federation Internationale de Gynecologie et d'Obstetrique (FIGO) on a regular basis. The 9th edition of the UICC TNM Classification of Malignant Tumours has recently been published. This review summarized the changes between the 8th and 9th edition. The evidence basis used for revision is described and referenced, with a focus on the changes in head and neck and lung cancers.
Deng C, Inoue K, Saechao C
… +3 more, Hansen J, Ritz B, Heck JE
Int J Cancer
· 2026 Jun · PMID 42260983
·
Publisher ↗
Thyroid diseases are common among women of reproductive age and may be related to childhood cancer among offspring, though the evidence is inconsistent. Using Danish registries, we conducted a population-based case-contr...Thyroid diseases are common among women of reproductive age and may be related to childhood cancer among offspring, though the evidence is inconsistent. Using Danish registries, we conducted a population-based case-control study to investigate the relationship between maternal thyroid diseases and medication use and childhood cancer among offspring. Cases (N = 2521) diagnosed between 1973 and 2016 were ascertained from the Danish Cancer Registry, and controls (N = 63,014) were randomly selected from the Central Population Registry and matched on sex and date of birth. Information on diagnoses and prescriptions was obtained from the National Patient Register and the National Prescription Register, respectively. Conditional logistic regression was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Goiter was associated with any cancer (OR = 2.08, 95% CI: 1.44, 3.00), leukemia (OR = 2.18, 95% CI: 1.13, 4.18), acute lymphoblastic leukemia (OR = 2.12, 95% CI: 1.02, 4.42), and lymphoma (OR = 3.06, 95% CI = 1.20, 7.82). There was no observed association between childhood cancer and maternal hypothyroidism or hyperthyroidism; however, these results were likely underpowered. No increased risk of cancer was observed for maternal thyroid medication use. Though the small sample size must be considered, the elevated risk of cancer with maternal thyroid diseases, especially goiter, was notable.
Vaeyens F, Hetzel JP, Abdullah K
… +12 more, Eggermont C, Olsen C, Mernberger M, Maes K, Vlaeminck J, Claus R, Vanisterbecq D, Hes F, Pichler M, Giron P, Timofeev O, Noeparast M
Int J Cancer
· 2026 Jun · PMID 42253180
·
Publisher ↗
Mutual exclusivity (ME) and co-occurrence (CO) of oncogenic mutations reflect functional antagonism or dependence and may inform therapeutic strategies. However, most studies overlook variant-level patterns. We performed...Mutual exclusivity (ME) and co-occurrence (CO) of oncogenic mutations reflect functional antagonism or dependence and may inform therapeutic strategies. However, most studies overlook variant-level patterns. We performed a comprehensive, cross-cohort analysis of BRAF, KRAS, and EGFR mutation subtypes using 64,807 cBioPortal tumor samples, 1570 cancer cell lines, and 2714 Belgian clinical cases. Across all datasets, CO was rare among class I BRAF, hydrolysis KRAS, and classical-like EGFR mutations. Pairwise variant-level analyses revealed novel ME interactions, including atypical variants, some overlapping with previously reported synthetically lethal pairs. We functionally validated the ME findings by inducing the expression of EGFR or BRAF in cell lines harboring KRAS or EGFR, respectively, resulting in growth inhibition. Overall survival analysis showed no consistent prognostic disadvantage for CO, except in EGFR-KRAS co-mutant NSCLC. These findings further refine the ME landscape of BRAF, KRAS, and EGFR variants, offering a variant-level reference to support mutation-informed precision oncology.
Bhatla N, Rol M, Singhal S
… +26 more, Hussain S, Patil A, Tanwar P, Singh S, Bhor VM, Munne K, Vashishtha R, Vashist S, Lucas E, Muwonge R, Ramírez AT, Singh A, Khan V, Rani J, Firdausi N, Sisodiya S, Wakchaure R, Picconi MA, Calderón A, Bell M, De Smet A, Vorsters A, Clifford GM, Chandra M, Kumar J, Basu P
Int J Cancer
· 2026 Jun · PMID 42252568
·
Publisher ↗
Persistent infection with high-risk human papillomavirus (HR-HPV) is the necessary cause of cervical cancer, with approximately 95% of cases attributable to eight most carcinogenic HPV types (16/18/31/33/35/45/52/58). Se...Persistent infection with high-risk human papillomavirus (HR-HPV) is the necessary cause of cervical cancer, with approximately 95% of cases attributable to eight most carcinogenic HPV types (16/18/31/33/35/45/52/58). Several HPV assays have recently been developed in India for use in cervical cancer screening, including reduced-valency tests targeting seven/eight oncogenic HPV types. We evaluated the clinical accuracy and reproducibility of four such assays: PathoDetect-HPV-14, HPV-Q (14 types), Truenat-HR-HPV-Plus (8 types), and PathoDetect-HPV-7 (7 types). Using the VALGENT framework, 1159 cervical samples from the ESTAMPA study conducted in Argentina and Costa Rica were analysed with the new assays. The samples included 97 cases of CIN2+ (19 CIN2, 72 CIN3, and 6 cancers). Assay performance was compared in a blinded manner with established reference tests (Cobas-4800 and Allplex-HPV-HR) and reduced-valency comparators. Sensitivity, specificity, agreement, and repeatability were assessed. Truenat-HR-HPV-Plus demonstrated a sensitivity of 80.4% (95% CI: 71.1-87.8) and specificity of 91.5% (95% CI: 89.5-93.2) for CIN2+. It met IARC validation criteria and showed non-inferior performance to Allplex-HPV-HR-8, with relative sensitivity of 1.03 (95% CI: 0.96-1.09) for CIN2+ and 1.00 (95% CI: 0.96-1.04) for CIN3+, and relative specificity of 0.99 (95% CI: 0.97-1.00) and 0.98 (95% CI: 0.97-1.00), respectively. Repeatability was 93.3% (κ = 0.79). PathoDetect-HPV-7 showed lower sensitivity (68.1%) with specificity of 89.0%. HPV-Q and PathoDetect-HPV-14 did not meet validation criteria. This study represents the first formal validation of reduced-valency HPV assays and demonstrates that Truenat-HR-HPV-Plus provides robust clinical performance with higher specificity than 14-valent assays, supporting its potential to improve screening efficiency and reduce unnecessary referrals.
Hyun CS, Wang R, Hong SH
… +2 more, Zhang X, Shin JI
Int J Cancer
· 2026 Jun · PMID 42252557
·
Publisher ↗
Classic mid-20th-century migrant studies demonstrated that gastric cancer risk declines after migration but does not fully converge to host-country levels, implicating early-life exposures and long disease latency. Wheth...Classic mid-20th-century migrant studies demonstrated that gastric cancer risk declines after migration but does not fully converge to host-country levels, implicating early-life exposures and long disease latency. Whether these migration-associated risk gradients remain detectable in contemporary low-incidence settings has not been systematically evaluated using modern U.S. cancer surveillance data. We analyzed SEER and state cancer registry data linked to U.S. Census-derived population denominators to estimate crude and age-adjusted gastric cancer incidence from 2010 to 2022 in California and New York. Asian populations were disaggregated into Chinese, Japanese, Korean, and Vietnamese subgroups. Temporal trends were assessed using Joinpoint regression, and U.S. incidence patterns were contextualized against country-of-origin incidence. Scenario-based extrapolations to 2035 were conducted. Gastric cancer incidence remained consistently higher among Asian populations than among non-Hispanic Whites, with age-adjusted incidence ranging from ~3.6-4.7 per 100,000 in non-Hispanic Whites versus 12-26 per 100,000 in Korean populations. Disaggregated analyses showed persistent differences across subgroups, with Korean populations consistently exhibiting the highest incidence. Incidence declined significantly over time in California (annual percent change ~-1% to -3%) but not in New York. Extrapolations suggest that a clinically meaningful burden will persist among high-risk subgroups through 2035. These findings demonstrate that migration-associated variation in gastric cancer risk remains detectable and prevention-relevant in contemporary U.S. populations, supporting migration-informed approaches to risk stratification and prevention.