OPC

Synergistic combinatorial antihyperlipidemic study of selected natural antioxidants; modulatory effects on lipid profile and endogenous antioxidants.

1. Lipids Health Dis. 2016 Sep 9;15(1):151. doi: 10.1186/s12944-016-0323-3. Synergistic combinatorial antihyperlipidemic study of selected natural antioxidants; modulatory effects on lipid profile and endogenous antioxidants. Hannan PA(1), Khan JA(2), Ullah I(1), Ullah S(1). Author information:

The natural tannins oligomeric proanthocyanidins and punicalagin are potent inhibitors of infection by SARS-CoV-2.

1. Elife. 2023 Aug 29;12:e84899. doi: 10.7554/eLife.84899. The natural tannins oligomeric proanthocyanidins and punicalagin are potent inhibitors of infection by SARS-CoV-2. Chen HF(1)(2), Wang WJ(2)(3), Chen CY(2), Chang WC(4), Hsueh PR(5), Peng SL(6)(7), Wu CS(1)(2), Chen Y(3)(8), Huang HY(1), Shen WJ(1), Wang SC(1)(2)(4)(9)(10), Hung MC(1)(2)(4)(9)(10)(11). Author information: (1)Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan. (2)Research Center for Cancer Biology, China Medical University, Taichung, Taiwan. (3)Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan. (4)Center for Molecular Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan. (5)Departments of Laboratory Medicine and Internal Medicine, China Medical University Hospital, School of Medicine, China Medical University, Taichung, Taiwan. (6)Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan. (7)Neuroscience and Brain Disease Center, China Medical University, Taichung, Taiwan. (8)Institute of New Drug Development, China Medical University, Taichung, Taiwan. (9)Cancer Biology and Precision Therapeutics Center, China Medical University, Taichung, Taiwan. (10)Department of Biotechnology, Asia University, Taichung, Taiwan. (11)Institute of Biochemistry and Molecular Biology, China Medical University, Taichung, Taiwan. Update of doi: 10.1101/2023.01.12.523465. The Coronavirus Disease 2019 (COVID-19) pandemic continues to infect people worldwide. While the vaccinated population has been increasing, the rising breakthrough infection persists in the vaccinated population. For living with the virus, the dietary guidelines to prevent virus infection are worthy of and timely to develop further. Tannic acid has been demonstrated to be an effective inhibitor of coronavirus and is under clinical trial. Here we found that two other members of the tannins family, oligomeric proanthocyanidins (OPCs) and punicalagin, are also potent inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with different mechanisms. OPCs and punicalagin showed inhibitory activity against omicron variants of SARS-CoV-2 infection. The water extractant of the grape seed was rich in OPCs and also exhibited the strongest inhibitory activities for viral entry of wild-type and other variants in vitro. Moreover, we evaluated the inhibitory activity of grape seed extractants (GSE) supplementation against SARS-CoV-2 viral entry in vivo and observed that serum samples from the healthy human subjects had suppressive activity against different variants of SARS-CoV-2 Vpp infection after taking GSE capsules. Our results suggest that natural tannins acted as potent inhibitors against SARS-CoV-2 infection, and GSE supplementation could serve as healthy food for infection prevention. Plain Language Summary: Since it first surfaced in late 2019, the COVID-19 pandemic has had a significant impact on people’s lives. While several vaccines have been created, infections have not disappeared. This is largely due to new variants of the virus responsible for the disease (SARS-CoV-2) emerging, which current vaccines do not work as well against. Indeed, several reports suggest that protection from the omicron variant wanes as shortly as four to six months after vaccination. Therefore, other strategies are needed to reduce the risk of SARS-CoV-2 infections. In 2022, researchers discovered that tannic acid blocked two proteins that SARS-CoV-2 needs to enter and replicate inside human cells. Tannic acid is part of the tannin family, which includes natural molecules found in plant-based meals and beverages. Here, Chen et al. – including some of the researchers involved in the 2022 studies – set out to find whether two other tannins found in nature (OPCs and punicalagin) could also inhibit SARS-CoV-2. Chen et al. administered tannic acid, OPCs and punicalagin to human cells cultured in a laboratory that had been infected with SARS-CoV-2. This revealed that all three tannins suppress the activity of the same proteins required for viral entry and replication, but to varying degrees suggesting that they block SARS-CoV-2 infections via different mechanisms. The compounds were also able to inhibit different variants of the virus, including omicron, from infecting the lab-grown cells. Further experiments revealed that water extracted from seeded grapes, which contains high levels of OPCs, could also block SARS-CoV-2 entry in the cell culture system. To test this further, Chen et al. gave 18 healthy individuals capsules containing different concentrations of grape seed extract and collected samples of their serum. The serum samples suppressed entry of different variants of SARS-CoV-2 in the cell culture system, with serums from subjects that received the higher dose having the greatest effect. These findings suggest that naturally occurring tannins can suppress multiple variants of SARS-CoV-2 from entering and replicating in cells. Consuming supplements of grape seed extract could potentially reduce the risk of SARS-CoV-2 infections. However, further experiments, including clinical trials, are needed to test this possibility. © 2023, Chen et al. DOI: 10.7554/eLife.84899 PMCID: PMC10465125 PMID: 37642993 [Indexed for MEDLINE] Conflict of interest statement: HC, WW, WC, YC, SW, MH registered as the inventor of a patent application based on inhibiting SARS-CoV-2 infection of punicalagin and OPC (ROC Patent No.111133318), CC, PH, SP, CW, HH, WS No competing interests declared

Randomized controlled trial of high-dose versus standard-dose vitamin D3 for prevention of aromatase inhibitor-induced arthralgia.

2. Breast Cancer Res Treat. 2019 Sep;177(2):427-435. doi: 10.1007/s10549-019-05319-4. Epub 2019 Jun 19. Randomized controlled trial of high-dose versus standard-dose vitamin D3 for prevention of aromatase inhibitor-induced arthralgia. Niravath P(1), Hilsenbeck SG(2), Wang T(2), Jiralerspong S(2), Nangia J(2), Pavlick A(2), Ademuyiwa F(3), Frith A(3), Ma C(3), Park H(3), Rigden C(3), Suresh R(3), Ellis M(2), Kent Osborne C(2), Rimawi MF(2). Author information: (1)Baylor College of Medicine, 6445 Main Street, OPC 24-346, Houston, TX, 77030, USA. paniravath@houstonmethodist.org. (2)Baylor College of Medicine, 6445 Main Street, OPC 24-346, Houston, TX, 77030, USA. (3)Washington University, St. Louis, MO, USA. PURPOSE: Half of hormone receptor-positive (HR+) breast cancer patients will develop joint pain, termed aromatase inhibitor-induced arthralgia (AIA), while taking aromatase inhibitor therapy. Though there is no universally accepted effective treatment for AIA, there has been some evidence to support high-dose vitamin D as a treatment. METHODS: We randomized post-menopausal women who were beginning adjuvant AI therapy to receive standard-dose vitamin D3 (800 IU daily for 52 weeks), or high-dose vitamin D3 (50,000 IU weekly for 12 weeks, followed by 2000 IU daily for 40 weeks). The primary end point was development of AIA. The trial was designed to enroll 184 patients. This futility analysis was performed after 93 patients were enrolled. RESULTS: The high-dose vitamin D regimen was effective in raising serum vitamin D levels, but there was no significant difference in development of AIA between the two arms. In the high-dose arm, 25 patients (54%) developed AIA, compared to 27 patients (57%) in the standard-dose arm. The planned futility analysis was positive; thus, the study was terminated. Neither baseline vitamin D nor 12-week vitamin D level was predictive of AIA development. CONCLUSION: Although vitamin D levels were increased in the high-dose arm, there was no significant signal for benefit of high-dose vitamin D supplementation for AIA prevention in this unblinded trial. This study, along with several others, implies that vitamin D likely does not play a significant role in AIA for the majority of patients. DOI: 10.1007/s10549-019-05319-4 PMID: 31218477 [Indexed for MEDLINE]

Beyond stimulants: a systematic review of randomised controlled trials assessing novel compounds for ADHD.

3. Expert Rev Neurother. 2019 Jul;19(7):707-717. doi: 10.1080/14737175.2019.1628640. Epub 2019 Jun 26. Beyond stimulants: a systematic review of randomised controlled trials assessing novel compounds for ADHD. Nageye F(1), Cortese S(1)(2)(3)(4)(5). Author information: (1)a Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine , University of Southampton , Southampton , UK. (2)b Center for Innovation in Mental Health, Academic Unit of Psychology , University of Southampton , Southampton , UK. (3)c Solent NHS Trust , Southampton , UK. (4)d New York University Child Study Center , New York , NY , USA. (5)e Division of Psychiatry and Applied Psychology , School of Medicine, University of Nottingham , Nottingham , UK. Introduction: Despite stimulants being highly efficacious in short-term randomized controlled trials (RCTs), not all patients respond or can successfully tolerate them. A number of novel non-stimulant options are currently in the pipeline for the treatment of attention-deficit/hyperactivity disorder (ADHD). Areas covered: The authors conducted a systematic review of RCTs registered in ClinicalTrials.gov in the past 5 years (January 2014 and February 2019), supplemented by searches in PubMed, Web of Science, and drug manufacturer websites to find recent RCTs on novel non-stimulant ADHD medications. Expert opinion: The authors found 28 pertinent RCTs of compounds acting on a variety of biological targets, including Dasotraline, Viloxazine (SPN-812), Centanafadine SR (CTN SR), OPC-64005, Fasoracetam (NFC-1, AEVI-001), Metadoxine (MDX), Vortioxetine, Tipepidine Hibenzate, Oxytocin, Sativex (delta-9-tetrahydrocannabinol (THC) plus cannabidiol), Mazindol, and Molindone hydrochloride (SPN-810). Given the high effect size found in RCTs of stimulants in terms of efficacy on ADHD core symptoms, it is unlikely that these novel agents will show better efficacy than stimulants, at the group level. However, they may offer comparable or better tolerability. Additionally, agents acting on etiopathophysiological targets disrupted in specific subgroups of patients with ADHD will move forward the pharmacotherapy of ADHD from a 'one size fits all' to a 'precision medicine' approach. DOI: 10.1080/14737175.2019.1628640 PMID: 31167583 [Indexed for MEDLINE]

Aterofisiol(®) in carotid plaque evolution.

4. Drug Des Devel Ther. 2015 Jul 23;9:3877-84. doi: 10.2147/DDDT.S87609. eCollection 2015. Aterofisiol(®) in carotid plaque evolution. Amato B(1), Compagna R(1), Amato M(2), Gallelli L(3), de Franciscis S(4), Serra R(5). Author information: (1)Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, University Magna Graecia of Catanzaro, Catanzaro, Italy ; Department of Clinical Medicine and Surgery, University Federico II of Naples, Naples, Italy. (2)Department of Clinical Medicine and Surgery, University Federico II of Naples, Naples, Italy. (3)Department of Health Sciences, University of Catanzaro, Catanzaro, Italy. (4)Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, University Magna Graecia of Catanzaro, Catanzaro, Italy ; Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy. (5)Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, University Magna Graecia of Catanzaro, Catanzaro, Italy ; Department of Clinical Medicine and Surgery, University Federico II of Naples, Naples, Italy ; Department of Health Sciences, University of Catanzaro, Catanzaro, Italy ; Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy. BACKGROUND: In patients with carotid stenosis, the risk of plaque rupture is related to the composition of the atherosclerotic plaque rather than to its magnitude. In this regard, we evaluated the effects of a supplement, Aterofisiol,(®) containing omega-3 (EPA [eicosapen acid] DHA [docosahexaenoic acid]), vitamin K2, vitamin B6, vitamin B12, oligomeric proanthocyanidins (OPC) and resveratrol on the composition of atherosclerotic plaque and on neurological symptoms in patients with carotid stenosis undergoing carotid endarterectomy. METHODS: The study was randomized, prospective, and double-blinded. Eligible patients were of both sexes, with carotid stenosis >70% who underwent endarterectomy. Enrolled patients were randomly allocated to receive either one tablet of acetylsalicylic acid 100 mg (Cardioaspirin(®)) + one tablet of Aterofisiol every 24 hours or one tablet of Cardioaspirin + one tablet of placebo every 24 hours. Each treatment was started 30 days before the surgery and was stopped 5 days before the surgery. The plaques were removed "en bloc" using standard surgical technique. RESULTS: During the study period, 214 patients (135 men and 79 women) were enrolled for intent-to-treat and randomized in two groups: Group A: 107 patients (68 men and 39 women) were treated with Cardioaspirin + Aterofisiol. Group B: 107 patients (67 men and 40 women) were treated with Cardioaspirin + placebo. At the end of the study, 202 patients participated fully (103 patients in Group A and 99 patients in Group B), making up the protocol evaluation population (94.4%). The mean lipid content of removed plaques was significantly lower (P<0.05) in Group A. We recorded a significantly lower incidence of neurological symptoms in Group A in comparison with Group B (P<0.05). CONCLUSION: In the study, Aterofisiol showed to be effective in reducing the amounts of cholesterol and lipids in the plaques and in reducing adverse neurological events in the study group with respect to controls. DOI: 10.2147/DDDT.S87609 PMCID: PMC4517514 PMID: 26229448 [Indexed for MEDLINE]

A double-blind, randomized clinical trial of dietary supplementation on cognitive and immune functioning in healthy older adults.

5. BMC Complement Altern Med. 2014 Feb 4;14:43. doi: 10.1186/1472-6882-14-43. A double-blind, randomized clinical trial of dietary supplementation on cognitive and immune functioning in healthy older adults. Lewis JE(1), Melillo AB, Tiozzo E, Chen L, Leonard S, Howell M, Diaz J, Gonzalez K, Woolger JM, Konefal J, Paterson E, Barnes D. Author information: (1)Department of Psychiatry & Behavioral Sciences, University of Miami Miller School of Medicine, 1120 NW 14th Street, Miami, FL 33136, USA. jelewis@miami.edu. Erratum in BMC Complement Altern Med. 2014;14:332. BACKGROUND: Declining cognitive function is relatively common and increasingly prevalent. Studies have shown that different nutrients (e.g., Ginkgo biloba and vitamin E) appear to be effective at improving memory and concentration, while less is known about their effect on immunity. METHODS: This study investigated the effect of Ginkgo Synergy(®) plus Choline (n = 33) and OPC Synergy(®) plus Catalyn(®) (n = 31) versus placebo (n = 33) in a 6-month, randomized, double-blind trial on cognitive and immune functioning among English-speaking, non-smoking, healthy older adults. The Stroop Color and Word Test, Trail Making Test A and B, Controlled Oral Word Association, Hopkins Verbal Learning, Mini-Mental State Exam, and Digit Symbol were administered at baseline and 3 and 6 months follow-up to assess cognitive functioning. Cytokines and growth factors were measured at baseline and 6 months to assess inflammation and immune functioning. Data were analyzed with linear mixed modeling. RESULTS: No serious adverse events were noted in this study. According to time on the Trail Making Test-B, the Ginkgo Synergy(®) plus Choline arm showed improvement from baseline to 3 months follow-up (mean difference = 24.2; SE = 6.4; 95% CI: 8.6, 39.7; p = 0.01). On the Controlled Oral Word Association Trial-S, the scores significantly increased for the Ginkgo Synergy(®) plus Choline arm from baseline to 6 months follow-up (mean difference = 2.1; SE = 0.8; 95% CI: 0.2, 3.9; p < 0.05) and for the OPC Synergy(®) plus Catalyn(®) arm from baseline to 3 months follow-up (mean difference = 2.1; SE = 0.8; 95% CI: 0.2, 4.0; p < 0.05). Epidermal growth factor significantly decreased from baseline to 6 months follow-up for the Ginkgo Synergy(®) plus Choline arm (mean difference = 120.7; SE = 28.4; 95% CI: 62.6, 178.8; p < 0.001). CONCLUSIONS: Our study showed isolated and modest effects of a Ginkgo biloba plus choline-based formula on cognitive and immune functioning among healthy older adults with no history of significant cognitive deficits. Our trial was registered with clinicaltrials.gov (ID: NCT01672359). This study was supported by a grant from Standard Process, Inc. DOI: 10.1186/1472-6882-14-43 PMCID: PMC3916807 PMID: 24495355 [Indexed for MEDLINE]

Interferon-β treatment normalises the inhibitory effect of serum from multiple sclerosis patients on oligodendrocyte progenitor proliferation.

6. Neurosci Lett. 2010 Nov 19;485(2):107-11. doi: 10.1016/j.neulet.2010.08.075. Epub 2010 Sep 15. Interferon-β treatment normalises the inhibitory effect of serum from multiple sclerosis patients on oligodendrocyte progenitor proliferation. Kotsiari A(1), Voss EV, Pul R, Skripuletz T, Ragancokova D, Trebst C, Stangel M. Author information: (1)Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Interferon-beta (IFN-β) is an established therapy for relapsing-remitting multiple sclerosis (MS). However, the mode of action and the effect on oligodendrocytes are not yet clear. In this study, we examined the influence of an IFN-β therapy on the proliferation and differentiation of primary oligodendrocyte precursor cells (OPC) in mixed glial cultures. Mixed glial cultures were incubated for 5 days in medium supplemented with 10% of sera from healthy controls, untreated MS patients and IFN-β treated MS patients. Proliferation and differentiation of OPC were determined by immunocytochemistry. Proliferation of OPC was significantly inhibited by sera from untreated MS patients compared to healthy controls, while this effect was almost completely reversed by serum from IFN-β treated MS patients. No effect on OPC differentiation was observed. A prospective and longitudinal analysis of a second cohort of MS patients treated with IFN-β showed that the reversal of inhibition of OPC proliferation was evident after 12 months of treatment but not during the first 6 months. Thus, our results suggest that IFN-β treatment has the capacity to revert the inhibitory effect of serum from MS patients on OPC proliferation. It is currently not clear what this means for regenerative processes. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved. DOI: 10.1016/j.neulet.2010.08.075 PMID: 20816724 [Indexed for MEDLINE]

The effect of OPC Factor on energy levels in healthy adults ages 45-65: a phase IIb randomized controlled trial.

7. J Altern Complement Med. 2008 Jul;14(6):723-32. doi: 10.1089/acm.2007.0661. The effect of OPC Factor on energy levels in healthy adults ages 45-65: a phase IIb randomized controlled trial. LaRiccia PJ(1), Farrar JT, Sammel MD, Gallo JJ. Author information: (1)Penn-Presbyterian Medical Center, Philadelphia, PA, USA. lariccip@mail.med.upenn.edu OBJECTIVE: To determine the efficacy of the food supplement OPC Factor to increase energy levels in healthy adults aged 45 to 65. DESIGN: Randomized, placebo-controlled, triple-blind crossover study. SUBJECTS: Twenty-five (25) healthy adults recruited from the University of Pennsylvania Health System. INTERVENTIONS: OPC Factor,trade mark (AlivenLabs, Lebanon, TN) a food supplement that contains oligomeric proanthocyanidins from grape seeds and pine bark along with other nutrient supplements including vitamins and minerals, was in the form of an effervescent powder. The placebo was similar in appearance and taste. OUTCOME MEASURES: Five outcome measurements were performed: (1) Energy subscale scores of the Activation-Deactivation Adjective Check List (AD ACL); (2) One (1) global question of percent energy change (Global Energy Percent Change); (3) One (1) global question of energy change measured on a Likert scale (Global Energy Scale Change); 4. One (1) global question of percent overall status change (Global Overall Status Percent Change); and (5) One (1) global question of overall status change measured on a Likert scale (Global Overall Status Scale Change). RESULTS: There were no carryover/period effects in the groups randomized to Placebo/Active Product sequence versus Active Product/Placebo sequence. Examination of the AD ACL Energy subscale scores for the Active Product versus Placebo comparison revealed no significant difference in the intention-to-treat (IT) analysis and the treatment received (TR) analysis. However, Global Energy Percent Change (p = 0.06) and Global Energy Scale Change (p = 0.09) both closely approached conventional levels of statistical significance for the active product in the IT analysis. Global Energy Percent Change (p = 0.05) and Global Energy Scale Change (p = 0.04) reached statistical significance in the TR analysis. A cumulative percent responders analysis graph indicated greater response rates for the active product. CONCLUSIONS: OPC Factor may increase energy levels in healthy adults aged 45-65 years. A larger study is recommended. Clinical Trials.gov identifier: NCT03318019. DOI: 10.1089/acm.2007.0661 PMCID: PMC3153864 PMID: 18684077 [Indexed for MEDLINE]

Improvement in circulation and in cardiovascular risk factors with a proprietary isotonic bioflavonoid formula OPC-3.

8. Angiology. 2008 Aug-Sep;59(4):408-14. doi: 10.1177/0003319708321801. Epub 2008 Jul 15. Improvement in circulation and in cardiovascular risk factors with a proprietary isotonic bioflavonoid formula OPC-3. Cesarone MR(1), Di Renzo A, Errichi S, Schönlau F, Wilmer JL, Blumenfeld J. Author information: (1)Department of Biomedical Science, G D'Annunzio University Chieti, Pescara, Italy. This study investigated the efficacy of isotonic bioflavonoid supplementation, OPC-3 on 61 individuals presenting with risk factors meeting the criteria for metabolic syndrome. Subjects were supplemented with a proprietary isotonic bioflavonoid OPC-3 or placebo over 2 months. Plasma oxidative stress status was significantly lowered by 10.1% with OPC-3. All major cardiovascular risk factors were improved with blood pressure, total cholesterol, and fasting blood glucose lowered. OPC-3 significantly improved endothelial function as evaluated by increased vasorelaxation in reactive hyperemia and enhanced diastolic carotid artery flow. Cardiac ultrasound scanning revealed a significant increase of left ventricular ejection fraction. Skin microcirculation was enhanced, and better tissue perfusion led to significantly increased transcutaneous oxygen partial pressure and decreased pCO(2). With OPC-3 a dramatic and significant plasma C-reactive protein decrease by 52.1% occurred. Individuals may improve key cardiovascular risk factors by daily supplementation with the bioflavonoid OPC-3 as an important part of a healthier lifestyle. DOI: 10.1177/0003319708321801 PMID: 18628275 [Indexed for MEDLINE]

Evaluation of the functional efficacy of an antioxidative probiotic in healthy volunteers.

9. Nutr J. 2005 Aug 4;4:22. doi: 10.1186/1475-2891-4-22. Evaluation of the functional efficacy of an antioxidative probiotic in healthy volunteers. Songisepp E(1), Kals J, Kullisaar T, Mändar R, Hütt P, Zilmer M, Mikelsaar M. Author information: (1)Department of Microbiology, University of Tartu, 50411 Tartu, Estonia. esongisepp@yahoo.fr BACKGROUND: In persons without clinical symptom it is difficult to assess an impact of probiotics regarding its effect on health. We evaluated the functional efficacy of the probiotic Lactobacillus fermentum ME-3 in healthy volunteers by measuring the influence of two different formulations on intestinal lactoflora, fecal recovery of the probiotic strain and oxidative stress markers of blood and urine after 3 weeks consumption. METHODS: Two 3-week healthy volunteer trials were performed. Open placebo controlled (OPC) study participants (n = 21) consumed either goat milk or by L. fermentum ME-3 fermented goat milk (daily dose 11.8 log CFU (Colony Forming Units). Double blind randomised placebo controlled (DBRP) study participants (n = 24) received either capsules with L. fermentum ME-3 (daily of dose 9.2 CFU) or placebo capsules. The faecal lactoflora composition, faecal ME-3 recovery, effect of the consumption on intestinal lactoflora, and oxidative stress markers of blood (total antioxidative activity; total antioxidative status and glutathione red-ox ratio) was measured. RESULTS: ME-3 was well tolerated and a significant increase in total faecal lactobacilli yet no predominance of ME-3 was detected in all study groups. Faecal recovery of ME-3 was documented by molecular methods only in fermented milk group, however the significant improvement of blood TAA (Total Antioxidative Activity) and TAS (Total Antioxidative Status) indices was seen both in case of fermented goat milk and capsules", yet glutathione re-ox ratio values decreased only in case of fermented by ME-3 goat milk. CONCLUSION: The functional efficacy of both consumed formulations of an antioxidative probiotic L. fermentum ME-3 is proved by the increase of the intestinal lactobacilli counts providing putative defence against enteric infections and by reduction of the oxidative stress indices of blood and urine of healthy volunteers. In non-diseased host the probiotic health claims can be assessed by improvement of some measurable laboratory indices of well-established physiological functions of host, e.g. markers of antioxidative defence system. DOI: 10.1186/1475-2891-4-22 PMCID: PMC1198254 PMID: 16080791 [Indexed for MEDLINE]

Update in medical therapy of ulcerative colitis: newer concepts and therapies.

10. J Clin Gastroenterol. 2005 Aug;39(7):557-69. doi: 10.1097/01.mcg.0000170735.43887.3a. Update in medical therapy of ulcerative colitis: newer concepts and therapies. Katz S(1). Author information: (1)Department of Medicine, New York University School of Medicine, New York, NY, USA. SeymourKatz@optonline.net Erratum in J Clin Gastroenterol. 2005 Oct;39(9):843. Recent advances in the pathogenesis of ulcerative colitis recognize the interface of genetic susceptibility, environmental factors (eg, gut microflora), and an altered host's immune response. The meteoric evolution of new therapies designed to address these pathogenetic factors may lead to confusing and often confounding treatment programs. This review is designed to assist the practitioner when in [corrected] incorporating new or novel therapies into a treatment program. These decisions are based on new clinical trial data and the experience of seasoned gastroenterologists with established remedies. NEWER CONCEPTS AND THERAPIES IN UC 5-ADA-- 1. Remains drug of choice for induction and maintenance of remission in mild to moderate IC.1,2 2. Rare but increased incidence of renal disease exists but benefits outweigh risks.18-20 3. Chemoprevention of colorectal cancer in UC is promising and may be related to higher dose and a lessened degree of inflammation.29-36 4. Bioequivalence of all USA 5-ASA is established. Choice of a 5-ASA preparation is not dependent on superiority of a particular mesalamine.3 Phosphodiesterase Inhibitor (OPC-6525)37: preliminary data promising Immunomodulators 6MP/AZA 1. long-term effect not waning51 2. concerns over lymphoma voiced but overall benefits outweigh risks64-70 3. 6MP metabolites measurements of increasing use52-56 Cyclosporine experience continues but serious adverse events remains.105-114 Biologics Infliximab--somewhat disappointing in CUC, awaiting RCT87-92 Basiliximab--useful as "steroid sensitizer" in previously steroid resistant patients118-120 Visilizumab--promising as alternative to cyclosporin in server U.C.115-117 Apheresis--and emerging "non-drug" treatment alternative121-135 Probiotics--Useful in pouchitis and some mild to moderate U.C.94-98, 154 ISIS topical therapy useful in early pilot study (pouchitis)151 Budesonide (pouchitis)147 Antibiotics (pouchitis)140-146 [corrected] DOI: 10.1097/01.mcg.0000170735.43887.3a PMID: 16000921 [Indexed for MEDLINE]

Oropharyngeal cancer risk groups in the United States: a meta-analysis and SEER analysis.

11. BMC Cancer. 2025 Sep 30;25(1):1441. doi: 10.1186/s12885-025-14904-4. Oropharyngeal cancer risk groups in the United States: a meta-analysis and SEER analysis. Bandala-Jacques A(1), Saldanha IJ(1)(2), D'Souza G(3). Author information: (1)Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street. Baltimore, Baltimore, 21205, MD, USA. (2)Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. (3)Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street. Baltimore, Baltimore, 21205, MD, USA. gdsouza2@jhu.edu. BACKGROUND: Incidence of oropharyngeal cancer (OPC) in the United States (US) has increased significantly due to human papillomavirus infections. This study characterized OPC incidence rates (IRs) by subgroups to identify high-risk populations for future screening efforts. METHODS: We conducted a comprehensive analysis comprising a systematic review and meta-analysis of studies published since 2000 reporting OPC IRs in the US, supplemented by a primary analysis of data from the Surveillance, Epidemiology, and End Results (SEER) program. From each source, we extracted cases and person-years to calculate IRs per 100,000 person-years (PY). Data from 11 studies selected for meta-analysis were analyzed using random-effects models. We stratified analyses by sex, age, race/ethnicity, and HIV status, as available. RESULTS: The meta-analysis found an overall OPC IR of 8.2 per 100,000 PY. Men had four times the incidence of OPC than women (13.4 and 3.6 per 100,000 PY, respectively). People living with HIV (PLWH) had the highest IR (27.6 per 100,000 PY), particularly men LWH (35.2 per 100,000 PY, compared to 12.4 in women LWH). SEER data confirmed sex differences, with low incidence in men < 50 years and in women of all ages, and a peak IR among men 60-79 years (32.4 per 100,000 PY). Among men aged 60-79, IRs were higher among White, Black, and American Indian/Alaskan Native (25.7-39.6 per 100,000 PY) than Hispanic/Latino or Asian American/Pacific Islander men (8.8-16.7 per 100,000 PY). CONCLUSIONS: Men aged 50-79 years and PLWH are at highest risk for OPC, with IRs comparable with or exceeding those of other HPV-associated cancers in the US. Any future screening efforts should prioritize these groups while excluding low-risk populations, such as women and individuals < 50 years. REGISTRATION: PROSPERO CRD42024588671. © 2025. The Author(s). DOI: 10.1186/s12885-025-14904-4 PMCID: PMC12482110 PMID: 41029528 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Knowledge of HPV and its association with oropharyngeal cancer among dental students: a systematic review and meta-analysis.

12. Front Oral Health. 2025 May 22;6:1604925. doi: 10.3389/froh.2025.1604925. eCollection 2025. Knowledge of HPV and its association with oropharyngeal cancer among dental students: a systematic review and meta-analysis. Albusairi K(1), Mandani B(1), Bouresly W(1), Brahmbhatt Y(2), Alqaderi H(3)(4), Alhazmi H(5)(6). Author information: (1)Kuwait Ministry of Health, Kuwait City, Kuwait. (2)Tufts University School of Dental Medicine, Boston, MA, United States. (3)Department of Public Health, Tufts University School of Dental Medicine, Boston, MA, United States. (4)Dasman Diabetes Institute, Kuwait City, Kuwait. (5)Division of Pediatric Dentistry, Department of Preventive Dentistry, Faculty of Dentistry, Umm Al-Qura University, Mecca, Saudi Arabia. (6)Department of Oral Health Policy and Epidemiology, Harvard School of Dental Medicine, Boston, MA, United States. Erratum in Front Oral Health. 2026 Mar 12;7:1815414. doi: 10.3389/froh.2026.1815414. BACKGROUND: Human papillomavirus (HPV) infection is a significant risk factor for oropharyngeal cancer (OPC), yet dental students' knowledge of this association varies widely. Given the critical role dentists play in early detection and prevention, understanding their level of knowledge is essential. This study systematically reviews existing research to assess dental students' awareness of HPV and its link to OPC. METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed, ProQuest, and Web of Science databases were searched for studies published up to August 2023. The Newcastle-Ottawa Scale was used to evaluate study quality. A random effects model was applied to calculate pooled prevalence with 95% confidence intervals. RESULTS: Sixteen studies, comprising 6,345 participants, were included. The pooled analysis showed that 69% of dental students had general knowledge of HPV (range: 56%-96.5%; 95% CI: 0.56-0.81), while 77% recognized its association with OPC (range: 18%-96.4%; 95% CI: 0.63-0.89). Significant heterogeneity was observed across studies (Q = 646.34, P < 0.001 for HPV; Q = 804.07, P < 0.001 for HPV-OPC). CONCLUSION: Knowledge gaps among dental students may hinder prevention efforts. Standardized education in dental curricula is crucial to ensure future dentists are well-prepared to address HPV-related conditions and promote early detection in clinical practice. © 2025 Albusairi, Mandani, Bouresly, Brahmbhatt, Alqaderi and Alhazmi. DOI: 10.3389/froh.2025.1604925 PMCID: PMC12137295 PMID: 40476005 Conflict of interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Toxicity and Oncologic Outcomes of Proton Radiotherapy for Oropharyngeal Cancer: A Systematic Review and Meta-Analysis.

13. Cureus. 2025 Feb 11;17(2):e78849. doi: 10.7759/cureus.78849. eCollection 2025 Feb. Toxicity and Oncologic Outcomes of Proton Radiotherapy for Oropharyngeal Cancer: A Systematic Review and Meta-Analysis. Razavian NB(1), Shenker RF(2), Smith S(3), D'Agostino RB Jr(3), Hughes RT(4). Author information: (1)Radiation Oncology, Moffitt Cancer Center, Tampa, USA. (2)Radiation Oncology, Intermountain Health, Salt Lake City, USA. (3)Biostatistics, Wake Forest School of Medicine, Winston-Salem, USA. (4)Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, USA. Intensity-modulated radiotherapy (IMRT) for oropharyngeal cancer (OPC) is associated with acute and late toxicities that impact patient quality of life. Proton radiotherapy (PRT) can reduce exposure to surrounding tissues, but the clinical magnitude of this advantage is unclear. A systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Included studies reported toxicity or oncologic outcomes from patients treated with PRT for OPC. Pooled outcomes were estimated using random-effects models. Comparisons between PRT and IMRT were performed using log odds ratios. Primary outcomes were the pooled rates of adverse events, overall survival (OS), and progression-free survival (PFS). A total of 18 studies (16 retrospective, two prospective) consisting of 956 patients were identified. Pooled rates of acute grade 3+ toxicities were as follows: dermatitis 19%, mucositis 32%, xerostomia 1.3%, dysphagia 13%, and weight loss 1.4%. The pooled rate of acute hospitalizations was 10%. Among studies reporting late toxicities, the rates of grade 3+ xerostomia and dysphagia were 1.1% and 1.6%, respectively. Compared to IMRT, PRT was associated with lower rates of acute feeding tube use (21% versus 31%; P = 0.0012), but not long-term feeding tube use (1.4% versus 2.7%; P = 0.24). After PRT, OS at two and three years were 98% and 96%, while PFS at two and three years were 93% and 86%. PRT for patients with OPC is associated with favorable toxicity and oncologic outcomes. While randomized clinical trials are ongoing, these data provide additional evidence regarding the efficacy of PRT in the upfront treatment of OPC. Copyright © 2025, Razavian et al. DOI: 10.7759/cureus.78849 PMCID: PMC11906207 PMID: 40084320 Conflict of interest statement: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Incremental net benefit of extending human papillomavirus vaccine to boys in oropharyngeal cancer burden: Meta-analysis of cost-effectiveness studies.

14. J Dent Sci. 2024 Oct;19(4):2045-2056. doi: 10.1016/j.jds.2024.05.032. Epub 2024 Jun 8. Incremental net benefit of extending human papillomavirus vaccine to boys in oropharyngeal cancer burden: Meta-analysis of cost-effectiveness studies. Pratama AP(1)(2), Chen SF(3), Liao SC(4), Su WC(3)(5), Yu JH(3)(6). Author information: (1)Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan. (2)Department of Public Health and Preventive Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia. (3)School of Dentistry, College of Dentistry, China Medical University, Taichung, Taiwan. (4)Department of Social Medicine, School of Medicine, China Medical University, Taichung, Taiwan. (5)Division of Oral and Maxillofacial Surgery, Department of Dentistry, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. (6)Orthodontics, Department of Dentistry, China Medical University Hospital, Taichung, Taiwan. BACKGROUND/PURPOSE: The incidence of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) is increasing worldwide. HPV vaccines have shown efficacy in preventing diseases in both males and females. Therefore, there is a need to develop cost-effective strategies for HPV vaccines to prevent HPV-related OPC. This meta-analysis aimed to evaluate cost-effectiveness using the global mean of incremental cost-effectiveness ratios compared to the willingness-to-pay threshold and incremental net benefits (INBs) of HPV vaccination strategies between boys' extension vaccine and girls only. These recommendations will be useful for countries that have not implemented universal HPV vaccines in national programs, such as Taiwan. MATERIALS AND METHODS: Studies evaluating the cost-effectiveness of HPV vaccination strategies in the prevention of OPC that included both sexes versus girls only were identified through the Cochrane Library, EMBASE, PubMed, ScienceDirect, and Web of Science databases on February 05, 2024, and a meta-analysis of pooled INBs was performed using a random-effects model. The outcome was an effective measurement of the OPC burden. The results are represented in USD (2024). RESULTS: Fifteen model analyses were included. All the studies were conducted in high-income countries. The global mean of incremental cost-effectiveness ratio was $39,553 (95% CI, $27,008-66,641) per quality-adjusted life years gained, which was below the global mean of the willingness-to-pay threshold of $65,473 (95% CI, $52,138-83,755). Pooled INBs of $9370 (95% CI, $5046-13,695; P < 0.001) favored the extended HPV in boys. CONCLUSION: HPV vaccination strategies that include boys are cost-effective compared to those with girls only in preventing OPC burden. By implementing a universal HPV vaccination program, countries can receive $9370 in additional monetary benefits per patient. Given its relevance to high-income countries, this study offers key insights that can aid policymakers in Taiwan. © 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V. DOI: 10.1016/j.jds.2024.05.032 PMCID: PMC11437266 PMID: 39347094 Conflict of interest statement: The authors have no conflict of interest relevant to this article.

Efficacy and safety of bedaquiline and delamanid in the treatment of drug-resistant tuberculosis in adults: A systematic review and meta-analysis.

15. Indian J Tuberc. 2024 Jan;71(1):79-88. doi: 10.1016/j.ijtb.2023.05.005. Epub 2023 May 12. Efficacy and safety of bedaquiline and delamanid in the treatment of drug-resistant tuberculosis in adults: A systematic review and meta-analysis. Ahmed SH(1), Haider H(2), Moeed A(2), Mahmood A(2), Shivani N(3), Shuja SH(2), Hayat J(2), Jamil B(4), Fatima R(5). Author information: (1)Department of Internal Medicine, Dow University of Health Sciences, Baba-e-Urdu Road, Karachi, 74200, Pakistan. Electronic address: hoorulain_ahmed97@hotmail.com. (2)Department of Internal Medicine, Dow University of Health Sciences, Baba-e-Urdu Road, Karachi, 74200, Pakistan. (3)Department of Medicine, Bedford Hospital, Bedford, Bedfordshire, United Kingdom. (4)Department of Medicine, Aga Khan University, National Stadium Road, Karachi, 74800, Pakistan. (5)Common Management Unit (TB, HIV/AIDS & Malaria), Islamabad, Pakistan. Multi and extensively drug-resistant tuberculosis is a grave cause of global public health concern due to its high mortality and limited treatment options. We conducted this systemic review and meta-analysis to evaluate the efficacy and safety of bedaquiline and delamanid, which have been added to the WHO-recommended regimen for treating drug-resistant tuberculosis. Electronic databases were searched from their inception until December 1st, 2021, for eligible studies assessing the efficacy and safety of bedaquiline and delamanid for treating drug-resistant tuberculosis. Binary outcomes were pooled using a DerSimonian-Laird random-effects model and arcsine transformation and reported on a log scale with a 95% confidence interval (CIs). Twenty-one studies were shortlisted in which bedaquiline, delamanid, and a combination of both were administered in 2477, 937, and 169 patients. Pooled culture conversion at 6 months was 0.801 (p < 0.001), 0.849 (p = 0.059) for bedaquiline and delamanid, respectively, and 0.823 (p = 0.017), concomitantly. In the bedaquiline cohort, the pooled proportion of all-cause mortality at 6 months was reported as 0.074 (p < 0.001), 0.031 (p = 0.372) in the delamanid cohort, and 0.172 in the combined cohort. The incidence of adverse events in the bedaquiline cohort ranged from 11.1% to 95.2%, from 13.2% to 86.2% in the delamanid cohort, and 92.5% in a study in the combined cohort. The incidence of QTC prolongation reported in each cohort is as follows: bedaquiline 0.163 (p < 0.001), delamanid 0.344 (p = 0.272) and combined 0.340 (p < 0.001). Our review establishes the efficacy of delamanid, bedaquiline, and their combined use in treating drug-resistant tuberculosis with reasonable rates of culture conversion, low mortality rates, and safety of co-administration, as seen with their effect on the QTc interval. Copyright © 2023 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved. DOI: 10.1016/j.ijtb.2023.05.005 PMID: 38296395 [Indexed for MEDLINE] Conflict of interest statement: Conflicts of interest The author has none to declare.

Causal association of serum biomarkers with oral cavity and oropharyngeal cancer: a mendelian randomization study.

16. BMC Oral Health. 2023 Dec 9;23(1):987. doi: 10.1186/s12903-023-03729-x. Causal association of serum biomarkers with oral cavity and oropharyngeal cancer: a mendelian randomization study. Liu W(#)(1), Liu Y(#)(1), Li P(1), Wang Z(1), Chen J(1), Liu H(2), Ye J(3). Author information: (1)Department of Otolaryngology, Head and Neck Surgery, Third Affiliated Hospital of Sun Yat-sen University, #600 Tianhe Road, Tianhe, Guangzhou, Guangdong, 510630, P.R. China. (2)Division of Pulmonary and Critical Care, Department of Internal Medicine, Third Affiliated Hospital, Sun Yat-sen University, #600 Tianhe Road, Tianhe, Guangzhou, Guangdong, 510630, P.R. China. liuhui27@mail.sysu.edu.cn. (3)Department of Otolaryngology, Head and Neck Surgery, Third Affiliated Hospital of Sun Yat-sen University, #600 Tianhe Road, Tianhe, Guangzhou, Guangdong, 510630, P.R. China. yejin@mail.sysu.edu.cn. (#)Contributed equally BACKGROUND: Observational epidemiological studies revealed that multiple serum biomarkers can be associated with the risk of oral and oropharyngeal cancer (OC/OPC). However, the causal relationship between them remains largely unknown. This study aimed to investigate the causal relationship between potential serum biomarkers and (OC/OPC). METHODS: A two-sample Mendelian randomization (MR) approach was performed to assess the causal association of 10 serum biomarkers with the risk of OC / OPC. Summary data on OC/OPC were obtained from a GWAS meta-analysis that included 2497 cases and 2928 controls. The TwoSampleMR package in R was used to perform MR analyzes. Inverse-variance weighted (IVW), Weighted median and MR-Egger methods were used to assess causal effects. RESULTS: Suggestive associations with increased risk of C-reactive protein (CRP) (OR 1.52, 95% CI 1.14 to 2.02), using the IVW method. MR-Egger regression suggested that directional pleiotropy was unlikely to bias the result (P = 0.19). The findings were robust to sensitivity analyzes. The risk of OC/OPC was not associated with serum 25-hydroxyvitamin D, HDL cholesterol, LDL cholesterol, total cholesterol, triglycerides, adiponectin, leptin, HbA1C and Insulin-like growth factor 1 (IGF 1). CONCLUSIONS: This study supports that CRP was causally associated with an increased risk of oral and oropharyngeal cancer. © 2023. The Author(s). DOI: 10.1186/s12903-023-03729-x PMCID: PMC10709950 PMID: 38071306 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no competing interests.

Characteristics of human papillomavirus infection among oropharyngeal cancer patients: A systematic review and meta-analysis.

17. Arch Oral Biol. 2024 Jan;157:105830. doi: 10.1016/j.archoralbio.2023.105830. Epub 2023 Oct 31. Characteristics of human papillomavirus infection among oropharyngeal cancer patients: A systematic review and meta-analysis. Cui M(1), Cheng J(2), Cheng H(3), Zhao M(4), Zhou D(4), Zhang M(4), Jia J(5), Luo L(6). Author information: (1)Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China; Department of Pathology, Weifang Medical University, Weifang, China. (2)Digestive Department, Shandong Second Provincial General Hospital, Jinan, China. (3)Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China. (4)Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China; School of Public Health, Jiamusi University, Jiamusi, China. (5)Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China; Department of Basic medicine, Jiamusi University, China. (6)Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China. Electronic address: jmsllm@163.com. OBJECTIVE: This study aimed to explore the characteristics of human papillomavirus (HPV) in oropharyngeal carcinoma (OPC), in order to provide a new theoretical basis for the prevention, treatment, and management of OPC. METHODS: The electronic databases were searched available publications relevant to HPV infection and OPC. Studies were collected until July, 2023. The effect sizes were combined using R 4.2.2 software. Subgroup and sensitivity analyses were performed to explore the sources of heterogeneity. Funnel plot and Egger's test were used to assess the publication bias. RESULTS: Seventy-one studies were included with 10,908 OPC patients. The pooled prevalence of HPV and HR-HPV infection was 44.22% and 43.94%, respectively. The genotypes of HR-HPV were HPV16 (37.24%), HPV33 (2.44%), HPV18 (1.64%), HPV35 (1.53%), and HPV58 (0.89%). The highest HPV infection was in North America (66.87%), Oceania (43.09%), and Europe (41.49%), lowest in Africa (4.89%). Females exhibited higher HPV infection (43.18% vs 34.59% in males). Top subsites of HPV infection was tonsil (45.78%), followed by base of tongue (36.66%). Infection was higher in OPC patients aged > 60 (38.15%) than < 60 (34.73%). The prevalence of HPV infection in stage I-II of OPC patients is higher than that in stage III-IV. CONCLUSIONS: HPV genotyping (16, 18, 33, 35, 58) is a key factor in the prevention and treatment of OPC. Identifying tonsils, base of tongue, and soft palate as common subsites to improve early detection. Elderly women with high HPV infection require attention to risk management and health education for prevention. Copyright © 2023 Elsevier Ltd. All rights reserved. DOI: 10.1016/j.archoralbio.2023.105830 PMID: 37924712 [Indexed for MEDLINE] Conflict of interest statement: Declaration of Competing Interest The authors declare that they have no competing interests. Disclosure statement No potential conflict of interest was reported by the author(s).

Radiological Study of Atlas Arch Defects with Meta-Analysis and a Proposed New Classification.

18. Asian Spine J. 2023 Oct;17(5):975-984. doi: 10.31616/asj.2023.0030. Epub 2023 Aug 28. Radiological Study of Atlas Arch Defects with Meta-Analysis and a Proposed New Classification. Suphamungmee W(1), Yurasakpong L(1)(2)(3), Poonudom K(1)(3)(4), Tubbs RS(5)(6)(7)(8)(9), Iwanaga J(5)(6)(10)(11), Kruepunga N(1)(3), Chaiyamoon A(2), Suwannakhan A(1)(3). Author information: (1)Department of Anatomy, Faculty of Science, Mahidol University, Bangkok, Thailand. (2)Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok, Thailand. (3)In Silico and Clinical Anatomy Research Group (iSCAN), Department of Anatomy, Faculty of Science, Mahidol University, Bangkok, Thailand. (4)Vejnitatphattana School, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. (5)Department of Neurosurgery, Tulane University School of Medicine, New Orleans, LA, USA. (6)Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, LA, USA. (7)University of Queensland, Brisbane, Australia. (8)Department of Neurosurgery and Ochsner Neurosciences Institute, Ochsner Health System, New Orleans, LA, USA. (9)Department of Anatomical Sciences, St. George's University, St. George's, Grenada. (10)Department of Neurology, Tulane University School of Medicine, New Orleans, LA, USA. (11)Department of Anatomy, Kurume University School of Medicine, Fukuoka, Japan. This study consists of a retrospective cohort study, a systematic review, and a meta-analysis which were separately conducted. This study aimed to investigate the prevalence of atlas arch defects, generate an evidence-based synthesis, and propose a common classification system for the anterior and combined atlas arch defects. Atlas arch defects are well-corticated gaps in the anterior or posterior arch of the atlas. When both arches are involved, it is known as a combined arch defect. Awareness of these defects is essential for avoiding complications during surgical procedures on the upper spine. The prevalence of arch defects was investigated in an open-access OPC-Radiomics (Radiomic Biomarkers in Oropharyngeal Carcinoma) dataset comprising 606 head and neck computed tomography scans from oropharyngeal cancer patients. A systematic review and meta-analysis were performed to generate prevalence estimates of atlas arch defects and propose a classification system for the anterior and combined atlas arch defects. The posterior arch defect was found in 20 patients (3.3%) out of the 606 patients investigated. The anterior arch defect was not observed in any patient, while a combined arch defect was observed in one patient (0.2%). A meta-analysis of 13,539 participants from 14 studies, including the present study, yielded a pooled-posterior arch defect prevalence of 2.07% (95% confidence interval [CI], 1.22%-2.92%). The prevalences of anterior and combined arch defects were 0.00% (95% CI, 0.00%-0.10%) and 0.14% (95% CI, 0.04%-0.25%), respectively. The anterior and combined arch defects were classified into five subtypes based on their morphology and frequency. The present study showed that atlas arch defects were present in approximately 2% of the general population. For future studies, larger sample sizes should be used for studying arch defects to avoid the small-study effect and to predict the prevalence accurately. DOI: 10.31616/asj.2023.0030 PMCID: PMC10622819 PMID: 37634902 Conflict of interest statement: The present study did not meet the criteria for ethical approval according to the self-assessment form issued by the Mahidol University Central Institutional Review Board (MU-CIRB). Data sharing will be available upon reasonable request to the corresponding author. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Furthermore, the authors declare no conflicts of interest in this manuscript. Conflict of Interest No potential conflict of interest relevant to this article was reported.

Delta-radiomics-based models for toxicity prediction in radiotherapy: A systematic review and meta-analysis.

19. J Med Imaging Radiat Oncol. 2023 Aug;67(5):564-579. doi: 10.1111/1754-9485.13546. Epub 2023 Jun 13. Delta-radiomics-based models for toxicity prediction in radiotherapy: A systematic review and meta-analysis. Tan D(1), Mohamad Salleh SA(1), Manan HA(2), Yahya N(1). Author information: (1)Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia. (2)Functional Image Processing Laboratory, Department of Radiology, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia. INTRODUCTION: Delta-radiomics models are potentially able to improve the treatment assessment than single-time point features. The purpose of this study is to systematically synthesize the performance of delta-radiomics-based models for radiotherapy (RT)-induced toxicity. METHODS: A literature search was performed following the PRISMA guidelines. Systematic searches were performed in PubMed, Scopus, Cochrane and Embase databases in October 2022. Retrospective and prospective studies on the delta-radiomics model for RT-induced toxicity were included based on predefined PICOS criteria. A random-effect meta-analysis of AUC was performed on the performance of delta-radiomics models, and a comparison with non-delta radiomics models was included. RESULTS: Of the 563 articles retrieved, 13 selected studies of RT-treated patients on different types of cancer (HNC = 571, NPC = 186, NSCLC = 165, oesophagus = 106, prostate = 33, OPC = 21) were eligible for inclusion in the systematic review. Included studies show that morphological and dosimetric features may improve the predictive model performance for the selected toxicity. Four studies that reported both delta and non-delta radiomics features with AUC were included in the meta-analysis. The AUC random effects estimate for delta and non-delta radiomics models were 0.80 and 0.78 with heterogeneity, I2 of 73% and 27% respectively. CONCLUSION: Delta-radiomics-based models were found to be promising predictors of predefined end points. Future studies should consider using standardized methods and radiomics features and external validation to the reviewed delta-radiomics model. © 2023 Royal Australian and New Zealand College of Radiologists. DOI: 10.1111/1754-9485.13546 PMID: 37309680 [Indexed for MEDLINE]

Evidence-based objective performance criteria for the evaluation of hip and knee replacement devices and technologies.

20. Int J Surg. 2023 May 1;109(5):1125-1135. doi: 10.1097/JS9.0000000000000169. Evidence-based objective performance criteria for the evaluation of hip and knee replacement devices and technologies. Nieuwenhuijse MJ(1)(2), Randsborg PH(3), Hyde JH(4), Xi W(2), Franklin P(5), Sun L(6)(7), Zheng X(2), Banerjee S(2), Mao J(2), Aryal S(2), Chan P(8), Chen A(2), Liebeskind A(2), Bonangelino P(6)(7), Voorhorst P(9), Gressler LE(6)(7), Devlin V(6)(7), Peat R(6)(7), Marinac-Dabic D(6)(7), Paxton E(8), Sedrakyan A(2). Author information: (1)Department of Orthopedic Surgery, Amphia Hospital, Breda, The Netherlands. (2)Department of Population Health Sciences, Weill Cornell Medical College, New York, New York. (3)Department of Orthopaedic Surgery, Akershus University Hospital, Lørenskog, Norway. (4)Internal Medicine, University of Tennessee, Chattanooga, Tennessee. (5)Department of Medical Social Sciences Northwestern University Feinberg School of Medicine. (6)Orthopedics Outcomes Research, FORCE-TJR, Chicago, Illinois. (7)Center for Devices and Radiological Health (CDRH), FDA, Silver Spring, Maryland. (8)Surgical Outcomes and Analysis, Kaiser Permanente, San Diego, California, USA. (9)Worldwide Clinical Research, DePuy Synthes Companies, a Johnson & Johnson Company, Fort Wayne, Indiana. BACKGROUND: Objective performance criteria (OPC) is a novel method to provide minimum performance standards and improve the regulated introduction of original or incremental device innovations in order to prevent patients from being exposed to potentially inferior designs whilst allowing timely access to improvements. We developed 2-year safety and effectiveness OPC for total hip and knee replacement (THR and TKR). METHODS: Analyses of large databases were conducted using various data sources: a systematic literature review; a direct data analysis from The Functional Outcomes Research for Comparative Effectiveness in Total Joint Replacement and Quality Improvement Registry (FORCE-TJR) and the Kaiser Permanente Implant Registry (KPIR); and claims data analyses from longitudinal discharge data in New York and California states. The literature review included U.S. patients (≥18 years) who received THR or TKR for primary end-stage osteoarthritis and prospectively collected data on patient-reported outcome measures (PROMs) from at least 100 subjects and/or 2-year implant survival for at least 250 implants. Random effects models were used for meta-analysis. RESULTS: Data were available from a total of 951 100 patients. After screening of 7979 abstracts, 294 studies underwent full-text review and 31 studies contributed to the evidence synthesis (333 995 implants). Direct data analysis of FORCE-TJR contributed 9223 joint replacement patients to the construction of OPC for effectiveness; KPIR contributed 262 044 patients for the construction of OPC for safety. Claims database analysis contributed 345 838 patients to the construction of safety OPC. OPC for safety were constructed for cumulative incidences of 2-year all-cause and septic revision (THR/TKR 2.0%/1.6% and 0.6%/0.7%), and OPC for effectiveness were constructed based on four disease-specific and three general health-related quality of life PROMs (HOOS/KOOS 87.1/80.6; HSS/KSS function 94.4/90.6; SF-12/SF-36, PCS 46.5/41.9, EQ-5D 0.88/0.84). CONCLUSION: This study is the first to construct a 2-year OPC for the safety and effectiveness of THR and TKR based on U.S. real-world data. Based on these OPC, potential benchmarks for (single-arm study) evaluation of new device innovations are suggested for a regulated and safe introduction to the (commercial) market. Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. DOI: 10.1097/JS9.0000000000000169 PMCID: PMC10389375 PMID: 37026873 [Indexed for MEDLINE] Conflict of interest statement: There are no conflicts of interest. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Reduced-dose radiation in human papillomavirus-associated oropharyngeal carcinoma can improve outcome: a systematic review and meta-analysis.

21. Ann Transl Med. 2022 Dec;10(24):1391. doi: 10.21037/atm-22-5935. Reduced-dose radiation in human papillomavirus-associated oropharyngeal carcinoma can improve outcome: a systematic review and meta-analysis. Yang MQ(#)(1), Liu YC(#)(2), Sui JD(#)(1)(3), Jin F(1)(3), Li D(3), Zhang L(3), Wang NH(3), Xie Y(1), Wang Y(1)(2)(3), Wu YZ(1)(2)(3). Author information: (1)Radiation Oncology Center, Chongqing University Cancer Hospital, Chongqing, China. (2)College of Bioengineering, Chongqing University, Chongqing, China. (3)College of Medicine, Chongqing University, Chongqing, China. (#)Contributed equally BACKGROUND: Despite its effectiveness, the standard course of chemoradiation for the treatment of human papillomavirus (HPV)-related oropharyngeal carcinoma (OPC) results in considerable treatment-related adverse effects. Studies proved that HPV-positive OPC is very sensitive to radiotherapy. Using de-escalation therapy as a new strategy is critical to maintaining positive outcomes while alleviating side effects. However, some studies hold that reduced dose causes insufficient effect on tumor killing. We conducted this systematic review and meta-analysis of survival and adverse reactions in patients with HPV-related OPC by retrospective analysis and evaluated the therapeutic effect of reducing the radiation dose. METHODS: Data were double-selected and extracted by searching seven electronic databases, Original studies in all language treated HPV-associated OPC with reduced-dose and standard-dose therapies were included. Overall survival (OS), progression-free survival (PFS), and incidence rates of adverse events were obtained by pooling analyses. Statistical analyses were performed using RStudio Version 1.1.383 (RStudio, Boston, MA, USA) via the Meta-Analysis R Package (metafor). Heterogeneity was evaluated using the I2 statistic and the Cochran Q test. We used Stata (version 15.0) for forest graph. RESULTS: Thirteen studies were included in this meta-analysis, involving a dose range of 66-70 Gy for the standard treatment regimen and <66 Gy for the reduced-dose group. There was no significant difference in the age of the patients in the standard and the reduced treatment groups (60.9±5.9 vs. 58.6±2.4 years). Nine studies were included as standard cohort and thirteen studies were enrolled as reduced-dose cohort. The 2- and 3-year overall survival rates in the reduced-dose group (95.66% and 91.51%, respectively) were superior to those in the standard-dose group (88.36% and 87.46%, respectively). There was no significant difference in PFS between the two groups. A systematic review of articles on dose reduction and the standard dose was also conducted. The most common complication in reduced-dose radiation was oral mucositis (36.4%), followed by decreased white blood cell (WBC) count (30.5%) and dry mouth (29.1%). CONCLUSIONS: Reducing the radiation dose in patients with HPV-related OPC substantially alleviates the treatment toxicities and optimizes the quality of life of patients while at the same time maintaining favorable oncologic outcomes. 2022 Annals of Translational Medicine. All rights reserved. DOI: 10.21037/atm-22-5935 PMCID: PMC9843369 PMID: 36660712 Conflict of interest statement: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-5935/coif). JDS reports that the current study was supported by grants from the National Natural Science Foundation of China (No. 81802740), and the Chongqing Science and Health Joint Medical Research Project (No. 2022ZDXM028). YW reports that the current study was supported by grants from the National Natural Science Foundation of China (No. 81972857), and the Natural Science Foundation of Chongqing City (No. cstc2021jscx-msxm0029). The other authors have no conflicts of interest to declare.

Efficacy and Tolerability of Concomitant Use of Bedaquiline and Delamanid for Multidrug- and Extensively Drug-Resistant Tuberculosis: A Systematic Review and Meta-Analysis.

22. Clin Infect Dis. 2023 Apr 3;76(7):1328-1337. doi: 10.1093/cid/ciac876. Efficacy and Tolerability of Concomitant Use of Bedaquiline and Delamanid for Multidrug- and Extensively Drug-Resistant Tuberculosis: A Systematic Review and Meta-Analysis. Holmgaard FB(1)(2), Guglielmetti L(3)(4), Lillebaek T(5)(6), Andersen ÅB(7), Wejse C(1)(2), Dahl VN(1)(2)(5). Author information: (1)Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark. (2)Center for Global Health, Department of Public Health, Aarhus University (GloHAU), Aarhus, Denmark. (3)Sorbonne Université, INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, Paris, France. (4)AP-HP Sorbonne Université, Hôpital Pitié-Salpêtrière, Laboratoire de Bactériologie-Hygiène, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Paris, France. (5)International Reference Laboratory of Mycobacteriology, Statens Serum Institut, Copenhagen, Denmark. (6)Global Health Section, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. (7)Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark. The introduction of two novel drugs, bedaquiline and delamanid, has given hope for better and shorter treatments of drug-resistant tuberculosis. A systematic review was conducted to evaluate the efficacy and safety of concomitant bedaquiline and delamanid administration. Pooled estimates of World Health Organization-defined favorable treatment outcome and significant QTc-interval prolongation (QTc ≥500 ms or ≥60 ms increase from baseline) were calculated using a random-effects model. Thirteen studies including a total of 1031 individuals with multidrug-resistant/rifampicin-resistant tuberculosis who received bedaquiline and delamanid were included. The pooled estimate of favorable treatment outcome was 73.1% (95% confidence interval [CI]: 64.3-81.8%). Sputum culture conversion at 6 months ranged from 61% to 95%. Overall, the pooled proportion of QTc-prolongation was 7.8% (95% CI: 4.1-11.6%) and few cardiac events were reported (0.8%; n = 6/798). Rates of sputum culture conversion and favorable treatment outcome were high in patients treated concomitantly with bedaquiline and delamanid, and the treatment seemed tolerable with low rates of clinically significant cardiac toxicity. © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. DOI: 10.1093/cid/ciac876 PMID: 36331978 [Indexed for MEDLINE] Conflict of interest statement: Potential conflicts of interest . L. G. is a principal investigator of 2 phase III randomized controlled trials, funded by Unitaid and sponsored by Médecins Sans Frontières, testing shorter regimens for MDR/RR-TB including bedaquiline and delamanid. C. W. is on an advisory board for Pfizer on COVID-19 treatments (2 meetings in 2022 for which an honorarium was paid) and was recently lecturing on future pandemics for pulmonology specialists for Novartis (payment or honoraria). These sponsors had no role in the study design, data collection, data analysis, data interpretation, or writing of the manuscript. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Comparative Efficacy and Safety of Antifungal Agents in the Prophylaxis of Oropharyngeal Candidiasis among HIV-Infected Adults: A Systematic Review and Network Meta-Analysis.

23. Life (Basel). 2022 Mar 31;12(4):515. doi: 10.3390/life12040515. Comparative Efficacy and Safety of Antifungal Agents in the Prophylaxis of Oropharyngeal Candidiasis among HIV-Infected Adults: A Systematic Review and Network Meta-Analysis. Rajadurai SG(1), Maharajan MK(2), Veettil SK(3), Gopinath D(4). Author information: (1)School of Postgraduate Studies, International Medical University, Kuala Lumpur 57000, Malaysia. (2)Department of Pharmacy Practice, School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia. (3)Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT 84112, USA. (4)Clinical Oral Health Sciences, International Medical University, Kuala Lumpur 57000, Malaysia. The objective of the study was to compare the efficacy and safety of antifungal agents used in the prevention of oropharyngeal candidiasis among HIV-infected adults. A systematic search was conducted in four databases (MEDLINE, Scopus, CENTRAL, and Embase) for eligible randomized control trials (RCTs). The network meta-analyses (NMA) were performed using a random-effects model. Interventions were ranked based on the efficacy and safety using the surface under the cumulative ranking curve (SUCRA). The quality of evidence was assessed using the GRADE approach. From a total of 1574 studies screened, 7 RCTs comprising 959 participants were included in NMA. The use of fluconazole as a prophylactic agent was associated with a significant reduction in incidence of OPC compared to placebo (RR, 0.45 (95% CI: 0.27-0.77)) in HIV-infected adults. The overall quality of evidence was graded as moderate. Fluconazole was ranked the best antifungal for efficacy (SUCRA-95.6%) as well as safety (SUCRA-39.3%) in HIV-infected adults. Overall, the quality of evidence was graded as moderate. Fluconazole can be considered as an effective agent with a better safety profile for the prophylaxis of OPC in HIV-infected adults. However, similar to any other antimicrobial agent, the risk of possibility of resistance must be weighed against the benefits. DOI: 10.3390/life12040515 PMCID: PMC9025400 PMID: 35455006 Conflict of interest statement: The authors declare no conflict of interest.

Treatment de-escalation for HPV+ oropharyngeal cancer: A systematic review and meta-analysis.

24. Head Neck. 2022 May;44(5):1255-1266. doi: 10.1002/hed.27019. Epub 2022 Mar 3. Treatment de-escalation for HPV+ oropharyngeal cancer: A systematic review and meta-analysis. Petrelli F(1), Luciani A(1), Ghidini A(2), Cherri S(3), Gamba P(4), Maddalo M(5), Bossi P(6), Zaniboni A(3). Author information: (1)Oncology Unit, ASST Bergamo Ovest, Italy. (2)Oncology Unit, Casa di cura Igea, Milan, Italy. (3)Oncology Unit, Fondazione Poliambulanza, Brescia, Italy. (4)Otolaryngology Unit, Fondazione Poliambulanza, Brescia, Italy. (5)Department of Radiation Oncology, University of Brescia and Spedali Civili, Brescia, Italy. (6)Medical Oncology, Department of Medical and Surgical Specialties, Radiological Sciences, Public Health, University of Brescia, Brescia, Italy. Human Papillomavirus (HPV) related oropharyngeal carcinoma (OPC) carries a better prognosis compared with HPV-counterparts, thereby pushing the adoption of de-intensification treatment approaches as new strategies to preserve superior oncologic outcomes while minimizing toxicity. We evaluated the effect of treatment de-intensification in terms of overall survival (OS), progression-free survival (PFS), locoregional and distant control (LRC and DM) by selecting prospective or retrospective studies, providing outcome data with reduced intensification versus standard curative treatment in HPV+ OPC patients, with a systematic analysis till September 2020. The primary outcome of interest was OS. Secondary endpoints were PFS, LRC, and DM expressed as HR. A total of 55 studies (from 1393 screened references) were employed for quantitative synthesis for 38 929 patients. Among n = 48 studies with data available, de-intensified treatments reduced OS in HPV+ OPCs (HR = 1.33, 95% CI 1.17-1.52; p < 0.01). In de-escalated treatments, PFS was also decreased (HR = 2.11, 95% CI 1.65-2.69; p < 0.01). Compared with standard treatments, reduced intensity approaches were associated with reduced locoregional and distant disease control (HR = 2.51, 95% CI 1.75-3.59; p < 0.01; and HR = 1.9, 95% CI 1.25-2.9; p < 0.01). Chemoradiation improved survival in a definitive curative setting compared with radiotherapy alone (HR = 1.42, 95% CI 1.16-1.75; p < 0.01). When adjuvant treatments were compared, standard and de-escalation strategies provided similar OS. In conclusion, in patients with HPV+ OPC, de-escalation treatments should not be widely and agnostically adopted in clinical practice, as therein lies a concrete risk of offering a sub-optimal treatment to patients. © 2022 Wiley Periodicals LLC. DOI: 10.1002/hed.27019 PMID: 35238114 [Indexed for MEDLINE]

Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer.

25. Nat Commun. 2021 Oct 12;12(1):5945. doi: 10.1038/s41467-021-26151-9. Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer. Ferreiro-Iglesias A(1), McKay JD(2), Brenner N(3), Virani S(4), Lesseur C(4)(5), Gaborieau V(4), Ness AR(6)(7), Hung RJ(8), Liu G(9), Diergaarde B(10)(11), Olshan AF(12), Hayes N(13), Weissler MC(14), Schroeder L(3), Bender N(3), Pawlita M(3), Thomas S(7), Pring M(7), Dudding T(7), Kanterewicz B(11), Ferris R(11), Thomas S(8), Brhane Y(8), Díez-Obrero V(15), Milojevic M(4), Smith-Byrne K(4), Mariosa D(4), Johansson MJ(4), Herrero R(16), Boccia S(17)(18), Cadoni G(19)(20), Lacko M(21), Holcátová I(22), Ahrens W(23), Lagiou P(24), Lagiou A(25), Polesel J(26), Simonato L(27), Merletti F(28), Healy CM(29), Hansen BT(30), Nygård M(31), Conway DI(32), Wright S(33), Macfarlane TV(34), Robinson M(35), Alemany L(36)(37), Agudo A(36), Znaor A(38), Amos CI(39), Waterboer T(3), Brennan P(40). Author information: (1)Section of Genetics, Genetic Epidemiology Group, International Agency for Research on Cancer, World Health Organization, Lyon, France. ferreiroa@iarc.fr. (2)Section of Genetics, Genetic Cancer Susceptibility Group, International Agency for Research on Cancer, World Health Organization, Lyon, France. (3)Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. (4)Section of Genetics, Genetic Epidemiology Group, International Agency for Research on Cancer, World Health Organization, Lyon, France. (5)Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (6)National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol, Bristol, UK. (7)Bristol Dental School, University of Bristol, Bristol, UK. (8)Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada. (9)Lunenfeld-Tanenbaum Research Institute of Sinai Health System, University of Toronto, Toronto, ON, Canada. (10)Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA. (11)UPMC Hillman Cancer Center, Pittsburgh, PA, USA. (12)Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. (13)Division of Medical Oncology and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, USA. (14)Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, Chapel Hill, NC, USA. (15)Oncology Data Analytics Program, Catalan Institute of Oncology (ICO), Barcelona, Spain. (16)Section of Early Detection and Prevention, Prevention and Implementation Group, International Agency for Research on Cancer, World Health Organization, Lyon, France. (17)Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italy. (18)Department of Woman and Child Health and Public Health - Public Health Area, Fondazione Policlinico Universitario A.Gemelli IRCCS, Roma, Italy. (19)Department of Head and Neck Surgery, Institute of Clinical Otorhinolaryngology, Università Cattolica del Sacro Cuore, Roma, Italy. (20)Istituto di Clinica Otorinolaringoiatrica, Fondazione Policlinico Universitario A.Gemelli IRCCS, Roma, Italy. (21)Department of Otorhinolaryngology, Head and Neck Surgery, Maastricht University Medical Center, Maastricht, The Netherlands. (22)Institute of Hygiene and Epidemiology, Prague, Czech Republic. (23)University Bremen, Bremen, Germany. (24)School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. (25)School of Public Health, University of West Attica, Athens, Greece. (26)National Cancer Institute, IRCCS, Aviano, Italy. (27)University of Padova, Padova, Italy. (28)CeRMS and University of Turin, Turin, Italy. (29)Trinity College School of Dental Science, Dublin, Ireland. (30)Cancer Registry of Norway, Oslo, Norway. (31)Department of Research, Cancer Registry of Norway, Oslo, Norway. (32)School of Medicine, Dentistry, and Nursing, University of Glasgow, Glasgow, UK. (33)Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde, Glasgow, UK. (34)University of Aberdeen, Aberdeen, UK. (35)Centre for Oral Health Research, Newcastle University, Newcastle, UK. (36)Catalan Institute of Oncology/IDIBELL, Barcelona, Spain. (37)Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública-CIBERESP, Madrid, Spain. (38)Cancer Surveillance Section, International Agency for Research on Cancer, World Health Organization, Lyon, France. (39)Department of Medicine, Baylor College of Medicine, Houston, TX, USA. (40)Section of Genetics, Genetic Epidemiology Group, International Agency for Research on Cancer, World Health Organization, Lyon, France. gep@iarc.fr. Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conduct a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer (OCC)) and 5,256 controls. We detect four susceptibility loci pointing to a distinct genetic predisposition by HPV status. Our most notable finding in the HLA region, that is now confirmed to be specific of HPV(+)OPC risk, reveal two independent loci with strong protective effects, one refining the previously reported HLA class II haplotype association. Antibody levels against HPV16 viral proteins strongly implicate the protective HLA variants as major determinants of humoral response against L1 capsid protein or E6 oncoprotein suggesting a natural immune response against HPV(+)OPC promoted by HLA variants. This indicates that therapeutic vaccines that target E6 and attenuate viral response after established HPV infections might protect against HPV(+)OPC. © 2021. The Author(s). DOI: 10.1038/s41467-021-26151-9 PMCID: PMC8511029 PMID: 34642315 [Indexed for MEDLINE] Conflict of interest statement: R.F. has the following financial disclosures: Aduro Biotech, Inc (consulting); Astra-Zeneca/MedImmune (clinical trial, research funding); Bristol-Myers Squibb (advisory board, clinical trial, research funding); EMD Serono (advisory board); MacroGenics, Inc (advisory board); Merck (advisory board, clinical trial); Novasenta (consulting, stock, research funding); Numab Therapeutics AG (advisory board); Pfizer (advisory board); Sanofi (consultant); Tesaro (research funding) and Zymeworks, Inc (consultant). Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization. All other authors have no conflicts to disclose.