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Viruses Jun 2023Human papillomavirus (HPV) is causally associated with 5% of cancers, including cancers of the cervix, penis, vulva, vagina, anus and oropharynx. The most carcinogenic... (Review)
Review
Human papillomavirus (HPV) is causally associated with 5% of cancers, including cancers of the cervix, penis, vulva, vagina, anus and oropharynx. The most carcinogenic HPV is HPV-16, which dominates the types causing cancer. There is also sufficient evidence that HPV types 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 cause cervical cancer. The L1 protein, which, when assembled into virus-like particles, induces HPV-type-specific neutralising antibodies, forms the basis of all commercial HPV vaccines. There are six licensed prophylactic HPV vaccines: three bivalent, two quadrivalent and one nonavalent vaccine. The bivalent vaccines protect from HPV types 16 and 18, which are associated with more than 70% of cervical cancers. Prophylactic vaccination targets children before sexual debut, but there are now catch-up campaigns, which have also been shown to be beneficial in reducing HPV infection and disease. HPV vaccination of adults after treatment for cervical lesions or recurrent respiratory papillomatosis has impacted recurrence. Gender-neutral vaccination will improve herd immunity and prevent infection in men and women. HPV vaccines are immunogenic in people living with HIV, but more research is needed on the long-term impact of vaccination and to determine whether further boosters are required.
Topics: Adult; Male; Child; Humans; Female; Human Papillomavirus Viruses; Papillomavirus Infections; Vaccinology; Uterine Cervical Neoplasms; Papillomavirus Vaccines; Human papillomavirus 16; Vaccines, Combined
PubMed: 37515128
DOI: 10.3390/v15071440 -
Abdominal Radiology (New York) Sep 2023The Society of Abdominal Radiology's Colorectal and Anal Cancer Disease-Focused Panel (DFP) first published a rectal cancer lexicon paper in 2019. Since that time, the... (Review)
Review
The Society of Abdominal Radiology's Colorectal and Anal Cancer Disease-Focused Panel (DFP) first published a rectal cancer lexicon paper in 2019. Since that time, the DFP has published revised initial staging and restaging reporting templates, and a new SAR user guide to accompany the rectal MRI synoptic report (primary staging). This lexicon update summarizes interval developments, while conforming to the original lexicon 2019 format. Emphasis is placed on primary staging, treatment response, anatomic terminology, nodal staging, and the utility of specific sequences in the MRI protocol. A discussion of primary tumor staging reviews updates on tumor morphology and its clinical significance, T1 and T3 subclassifications and their clinical implications, T4a and T4b imaging findings/definitions, terminology updates on the use of MRF over CRM, and the conundrum of the external sphincter. A parallel section on treatment response reviews the clinical significance of near-complete response and introduces the lexicon of "regrowth" versus "recurrence". A review of relevant anatomy incorporates updated definitions and expert consensus of anatomic landmarks, including the NCCN's new definition of rectal upper margin and sigmoid take-off. A detailed review of nodal staging is also included, with attention to tumor location relative to the dentate line and locoregional lymph node designation, a new suggested size threshold for lateral lymph nodes and their indications for use, and imaging criteria used to differentiate tumor deposits from lymph nodes. Finally, new treatment terminologies such as organ preservation, TNT, TAMIS and watch-and-wait management are introduced. This 2023 version aims to serve as a concise set of up-to-date recommendations for radiologists, and discusses terminology, classification systems, MRI and clinical staging, and the evolving concepts in diagnosis and treatment of rectal cancer.
Topics: Humans; Rectal Neoplasms; Anus Neoplasms; Rectum; Neoplasm Staging; Magnetic Resonance Imaging; Radiology
PubMed: 37145311
DOI: 10.1007/s00261-023-03893-2 -
Cancers Oct 2023More and more studies have focused on the associations between human papillomavirus (HPV) infection and pan-cancers. However, current evidence is largely based on...
INTRODUCTION
More and more studies have focused on the associations between human papillomavirus (HPV) infection and pan-cancers. However, current evidence is largely based on retrospective studies, which are susceptible to confounding factors and do not enable the establishment of causal relationships.
METHODS
A bidirectional two-sample Mendelian randomization (MR) design was employed to thoroughly evaluate the causal relationships between HPV and 12 site-specific cancers except cervical cancer. Single nucleoside polymers (SNPs) with strong evidence from genome-wide association studies (GWAS) were selected from HPV exposure datasets and used as instrumental variables (IVs) in this study. For the MR analysis results, MR-Egger's intercept P test, MR-PRESSO global test, Cochran's Q test and a leave-one-out test were applied for sensitivity analysis. Using HPVTIMER, we also performed immune infiltration analyses in head and neck squamous cell carcinoma (HNSCC), oropharyngeal squamous cell carcinoma (OPSCC) and vulval squamous cell carcinoma (VSCC) to evaluate the tumor-immune microenvironment.
RESULTS
Based on the evidence of MR analysis, our study conclusively identified HPV16 as a risk factor implicated in the development of bladder cancer, colorectal cancer, and breast cancer, while HPV18 was identified as a risk factor for prostate cancer, ovarian cancer, lung cancer and breast cancer. The MR results also showed that HPV16 may be a protective factor for prostate cancer, anal cancer, lung cancer and oropharyngeal cancer, while HPV18 may be a protective factor for vaginal cancer.
CONCLUSION
An HPV infection may modulate the immune microenvironment and therefore has a potential inhibitory effect on the development of certain cancers. These conclusions provided new insights into the potential mechanisms of carcinogenesis and needed further research for validation.
PubMed: 37958321
DOI: 10.3390/cancers15215147 -
Annals of Surgery Oct 2023The aim of the present randomized controlled trial was to evaluate the superiority of indocyanine green fluorescence imaging (ICG-FI) in reducing the rate of anastomotic... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The aim of the present randomized controlled trial was to evaluate the superiority of indocyanine green fluorescence imaging (ICG-FI) in reducing the rate of anastomotic leakage in minimally invasive rectal cancer surgery.
BACKGROUND
The role of ICG-FI in anastomotic leakage in minimally invasive rectal cancer surgery is controversial according to the published literature.
METHODS
This randomized, open-label, phase 3, trial was performed at 41 hospitals in Japan. Patients with clinically stage 0-III rectal carcinoma less than 12 cm from the anal verge, scheduled for minimally invasive sphincter-preserving surgery were preoperatively randomly assigned to receive a blood flow evaluation by ICG-FI (ICG+ group) or no blood flow evaluation by ICG-FI (ICG- group). The primary endpoint was the anastomotic leakage rate (grade A+B+C, expected reduction rate of 6%) analyzed in the modified intention-to-treat population.
RESULTS
Between December 2018 and February 2021, a total of 850 patients were enrolled and randomized. After the exclusion of 11 patients, 839 were subject to the modified intention-to-treat population (422 in the ICG+ group and 417 in the ICG- group). The rate of anastomotic leakage (grade A+B+C) was significantly lower in the ICG+ group (7.6%) than in the ICG- group (11.8%) (relative risk, 0.645; 95% confidence interval 0.422-0.987; P =0.041). The rate of anastomotic leakage (grade B+C) was 4.7% in the ICG+ group and 8.2% in the ICG- group ( P =0.044), and the respective reoperation rates were 0.5% and 2.4% ( P =0.021).
CONCLUSIONS
Although the actual reduction rate of anastomotic leakage in the ICG+ group was lower than the expected reduction rate and ICG-FI was not superior to white light, ICG-FI significantly reduced the anastomotic leakage rate by 4.2%.
Topics: Humans; Indocyanine Green; Anastomotic Leak; Rectal Neoplasms; Perfusion; Optical Imaging; Anastomosis, Surgical
PubMed: 37218517
DOI: 10.1097/SLA.0000000000005907 -
Journal of Pharmaceutical and... Sep 2023Monoclonal antibody (mAb)-based therapies have been a major advance in oncology patient care, even though they represent a significant healthcare cost. Biosimilars,... (Review)
Review
Monoclonal antibody (mAb)-based therapies have been a major advance in oncology patient care, even though they represent a significant healthcare cost. Biosimilars, launched in Europe in 2004 are an economically attractive alternative to expensive originator biological drugs. They also increase the competitiveness of pharmaceutical development. This article focuses on the case of Erbitux® (cetuximab). This anti-EGFR (Epidermal Growth Factor Receptor) monoclonal antibody is indicated for metastatic colorectal cancer (2004) and squamous cell carcinoma of the head and neck (2006). However, despite the expiration of the patent in Europe in 2014 and estimated annual sales of 1.681 million US dollars in 2022, Erbitux® has not yet faced any approved biosimilar challenges in the United States or in Europe. Here, we outline the unique structural complexity of this antibody highlighted by advanced orthogonal analytical characterization strategies resulting in risks to demonstrate biosimilarity, which may explain the lack of Erbitux® biosimilars in the European and US markets to date. The development of Erbitux® biobetters are also discussed as alternative strategies to biosimilars. These biologics offer expected additional safety and potency benefits over the reference product but require a full pharmaceutical and clinical development as for New Molecular Entities.
Topics: Humans; United States; Cetuximab; Biosimilar Pharmaceuticals; Antibodies, Monoclonal; Neoplasms; Europe
PubMed: 37418870
DOI: 10.1016/j.jpba.2023.115544 -
Cell & Bioscience Mar 2024Glucose-lowering drug is associated with various cancers, but the causality with gastrointestinal cancer risk is rarely reported. We aimed to explore the causality...
BACKGROUND & AIMS
Glucose-lowering drug is associated with various cancers, but the causality with gastrointestinal cancer risk is rarely reported. We aimed to explore the causality between them in this Mendelian randomization (MR) study.
METHODS
Two-sample MR, summary-data-based (SMR), mediation MR, and colocalization analyses was employed. Ten glucose-lowering drug targets (PPARG, DPP4, GLP1R, INSR, SLC5A2, ABCC8, KCNJ11, ETFDH, GPD2, PRKAB1) and seven types of gastrointestinal cancer (anal carcinoma, cardia cancer, gastric cancer, hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), pancreatic cancer, rectum cancer) were included. Patients with gastrointestinal cancers from six different large GWAS databases, including the UK Biobank and Finnish cohorts were incorporated, for discovery and external validation. Meta-analysis was employed to integrate the results from both discovery and validation cohorts, thereby ensuring the reliability of findings.
RESULTS
ABCC8/KCNJ11 were associated with pancreatic cancer risk in both two-sample MR (odds ratio (OR): 15.058, per standard deviation unit (SD) change of glucose-lowering durg target perturbation equivalent to 1 SD unit of HbA lowering; 95% confidence interval (95% CI): 3.824-59.295; P-value = 0.0001) and SMR (OR: 1.142; 95% CI: 1.013-1.287; P-value = 0.030) analyses. The mediation effect of body mass index (OR: 0.938; 95% CI: 0.884-0.995; proportion of mediation effect: 3.001%; P-value = 0.033) on ABCC8/KCNJ11 and pancreatic cancer was uncovered. Strong connections of DPP4 with anal carcinoma (OR: 0.123; 95% CI: 0.020-0.745; P-value = 0.023) and ICC (OR: 7.733; 95% CI: 1.743-34.310; P-value = 0.007) were detected. PPARG was associated with anal carcinoma (OR: 12.909; 95% CI: 3.217-51.795; P-value = 0.0003), HCC (OR: 36.507; 95% CI: 8.929-149.259; P-value < 0.0001), and pancreatic cancer (OR: 0.110; 95% CI: 0.071-0.172; P-value < 0.0001). SLC5A2 was connected with pancreatic cancer (OR: 8.096; 95% CI: 3.476-18.857; P-value < 0.0001). Weak evidence indicated the connections of GLP1R, GPD2, and PRKAB1 with anal carcinoma, cardia cancer, ICC, and rectum cancer. In addition, the corresponding results were consistently validated in both the validation cohorts and the integrated outcomes.
CONCLUSIONS
Some glucose-lowering drugs were associated with gastrointestinal cancer risk, which might provide new ideas for gastrointestinal cancer treatment.
PubMed: 38504335
DOI: 10.1186/s13578-024-01214-8