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Ugeskrift For Laeger May 2024
Topics: Humans; Condylomata Acuminata; Male; Female; Anus Neoplasms
PubMed: 38847314
DOI: 10.61409/V72029 -
Viruses Apr 2024The human papillomavirus is the most common sexually transmitted infection in the world. Most HPV infections clear spontaneously within 2 years of infection; however,... (Review)
Review
The human papillomavirus is the most common sexually transmitted infection in the world. Most HPV infections clear spontaneously within 2 years of infection; however, persistent infection can result in a wide array of diseases, ranging from genital warts to cancer. Most cases of cervical, anal, and oropharyngeal cancers are due to HPV infection, with cervical cancer being one of the leading causes of cancer death in women worldwide. Screening is available for HPV and cervical cancer, but is not available everywhere, particularly in lower-resource settings. HPV infection disproportionally affects individuals living with HIV, resulting in decreased clearance, increased development of cancer, and increased mortality. The development of the HPV vaccine has shown a drastic decrease in HPV-related diseases. The vaccine prevents cervical cancer with near 100% efficacy, if given prior to first sexual activity. Vaccination uptake remains low worldwide due to a lack of access and limited knowledge of HPV. Increasing awareness of HPV and access to vaccination are necessary to decrease cancer and HPV-related morbidity and mortality worldwide.
Topics: Humans; Papillomavirus Infections; Papillomavirus Vaccines; Female; Uterine Cervical Neoplasms; Papillomaviridae; Neoplasms; Vaccination; Anus Neoplasms; HIV Infections; Oropharyngeal Neoplasms; Male; Human Papillomavirus Viruses
PubMed: 38793561
DOI: 10.3390/v16050680 -
Scientific Reports Jul 2023Naturally occurring canine cancers have remarkable similarities to their human counterparts. To better understand these similarities, we investigated 671 client-owned... (Comparative Study)
Comparative Study
Naturally occurring canine cancers have remarkable similarities to their human counterparts. To better understand these similarities, we investigated 671 client-owned dogs from 96 breeds with 23 common tumor types, including those whose mutation profile are unknown (anal sac carcinoma and neuroendocrine carcinoma) or understudied (thyroid carcinoma, soft tissue sarcoma and hepatocellular carcinoma). We discovered mutations in 50 well-established oncogenes and tumor suppressors, and compared them to those reported in human cancers. As in human cancer, TP53 is the most commonly mutated gene, detected in 22.5% of canine tumors overall. Canine tumors share mutational hotspots with human tumors in oncogenes including PIK3CA, KRAS, NRAS, BRAF, KIT and EGFR. Hotspot mutations with significant association to tumor type include NRAS G61R and PIK3CA H1047R in hemangiosarcoma, ERBB2 V659E in pulmonary carcinoma, and BRAF V588E (equivalent of V600E in humans) in urothelial carcinoma. Our findings better position canines as a translational model of human cancer to investigate a wide spectrum of targeted therapies.
Topics: Animals; Dogs; Oncogene Proteins; Mutation; Neoplasms; Humans; Antineoplastic Agents
PubMed: 37414794
DOI: 10.1038/s41598-023-37505-2 -
International Journal of Clinical... Aug 2023Human papillomavirus (HPV) is associated with 5% of all cancers globally at a range of body sites, including cervix, anus, penis, vagina, vulva, and oropharynx. These... (Review)
Review
Human papillomavirus (HPV) is associated with 5% of all cancers globally at a range of body sites, including cervix, anus, penis, vagina, vulva, and oropharynx. These cancers claim > 400,000 lives annually. The persistent infection of HPV and the function of viral oncogenes are the primary causes of HPV-related cancers. However, only some HPV-infected persons or infected lesions will progress to cancer, and the burden of HPV-associated cancer varies widely according to gender and the part of the body infected. The dissimilarity in infection rates at different sites can explain only a small part of the differences observed. Much responsibility likely sits with contributions of specific epithelial cells and the cellular microenvironment at infected sites to the process of malignant transformation, both of which affect the regulation of viral gene expression and the viral life cycle. By understanding the biology of these epithelial sites, better diagnosis/treatment/management of HPV-associated cancer and/or pre-cancer lesions will be provided.
Topics: Male; Female; Humans; Human Papillomavirus Viruses; Papillomavirus Infections; Neoplasms; Carcinogenesis; Papillomaviridae; Uterine Cervical Neoplasms; Tumor Microenvironment
PubMed: 37199886
DOI: 10.1007/s10147-023-02340-y -
Journal For Immunotherapy of Cancer Jan 2024Recent trials suggest that programmed cell death 1 (PD-1)-directed immunotherapy may be beneficial for some patients with anal squamous cell carcinoma and biomarkers...
BACKGROUND
Recent trials suggest that programmed cell death 1 (PD-1)-directed immunotherapy may be beneficial for some patients with anal squamous cell carcinoma and biomarkers predictive of response are greatly needed.
METHODS
This multicenter phase II clinical trial (NCT02919969) enrolled patients with metastatic or locally advanced incurable anal squamous cell carcinoma (n=32). Patients received pembrolizumab 200 mg every 3 weeks. The primary endpoint of the trial was objective response rate (ORR). Exploratory objectives included analysis of potential predictive biomarkers including assessment of tumor-associated immune cell populations with multichannel immunofluorescence and analysis of circulating tumor tissue modified viral-human papillomavirus DNA (TTMV-HPV DNA) using serially collected blood samples. To characterize the clinical features of long-term responders, we combined data from our prospective trial with a retrospective cohort of patients with anal cancer treated with anti-PD-1 immunotherapy (n=18).
RESULTS
In the phase II study, the ORR to pembrolizumab monotherapy was 9.4% and the median progression-free survival was 2.2 months. Despite the high level of HPV positivity observed with circulating TTMV-HPV DNA testing, the majority of patients had low levels of tumor-associated CD8+PD-1+ T cells on pretreatment biopsy. Patients who benefited from pembrolizumab had decreasing TTMV-HPV DNA scores and a complete responder's TTMV-HPV DNA became undetectable. Long-term pembrolizumab responses were observed in one patient from the trial (5.3 years) and three patients (2.5, 6, and 8 years) from the retrospective cohort. Long-term responders had HPV-positive tumors, lacked liver metastases, and achieved a radiological complete response.
CONCLUSIONS
Pembrolizumab has durable efficacy in a rare subset of anal cancers. However, despite persistence of HPV infection, indicated by circulating HPV DNA, most advanced anal cancers have low numbers of tumor-associated CD8+PD-1+ T cells and are resistant to pembrolizumab.
Topics: Humans; Retrospective Studies; Prospective Studies; Programmed Cell Death 1 Receptor; Papillomavirus Infections; Carcinoma, Squamous Cell; Anus Neoplasms; DNA; Antibodies, Monoclonal, Humanized
PubMed: 38272561
DOI: 10.1136/jitc-2023-008436 -
Human Vaccines & Immunotherapeutics Dec 2023Human papillomavirus (HPV) infection is associated with the risk of developing certain cancers, including cancers of the cervix, vulva, vagina, penis, anus, rectum, and...
Human papillomavirus (HPV) infection is associated with the risk of developing certain cancers, including cancers of the cervix, vulva, vagina, penis, anus, rectum, and oropharynx. In 2016, the bivalent HPV-16/18 vaccine was included in the Korea National Immunization Program. This vaccine protects against HPV types 16 and 18 and other oncogenic HPV types predominant in cervical and anal cancers. This post-marketing surveillance (PMS) study assessed the safety of the HPV-16/18 vaccine in Korea. The study was conducted in males and females aged between 9 and 25 years, from 2017 to 2021. Safety was measured in terms of frequency and intensity of adverse events (AEs), adverse drug reactions (ADRs), and serious adverse events (SAEs) after each vaccine dose. The safety analysis included all participants who were vaccinated as per prescribing information and who completed a 30-day follow-up after at least one dose. Data were collected using individual case report forms. The total safety cohort included 662 participants. A total of 220 AEs were reported in 144 subjects (21.75%), and there were 158 ADRs in 111 subjects (16.77%), with the most common being injection site pain in all cases. No SAEs or serious ADRs were reported. Most AEs were reported after the first dose and were injection site reactions with mild intensity that recovered. No individuals required hospitalization or an emergency department visit. Safety results showed that the HPV-16/18 vaccine was generally well tolerated in the Korean population, and no safety concerns were identified.ClinicalTrials.gov Identifier: NCT03671369.
Topics: Male; Female; Humans; Child; Adolescent; Young Adult; Adult; Human papillomavirus 16; Uterine Cervical Neoplasms; Papillomavirus Infections; Human papillomavirus 18; Papillomavirus Vaccines; Drug-Related Side Effects and Adverse Reactions; Injection Site Reaction; Product Surveillance, Postmarketing; Republic of Korea
PubMed: 36896702
DOI: 10.1080/21645515.2023.2184756 -
Strahlentherapie Und Onkologie : Organ... Aug 2023Primary radiochemotherapy (RCT) constitutes the standard of care for early- and advanced-stage anal carcinoma. This retrospective study investigates the impact of dose...
PURPOSE
Primary radiochemotherapy (RCT) constitutes the standard of care for early- and advanced-stage anal carcinoma. This retrospective study investigates the impact of dose escalation on colostomy-free survival (CFS), overall survival (OS), locoregional control (LRC), progression-free survival (PFS), and acute and late toxicities in patients with squamous cell anal cancer.
METHODS
Considered were the outcomes of 87 patients with anal cancer treated with radiation/RCT between May 2004 and January 2020 at our institution. Toxicities were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE version 5.0).
RESULTS
The 87 patients received treatment with a median boost of 63 Gy to the primary tumor. With a median follow-up of 32 months, the 3‑year CFS, OS, LRC, and PFS were 79.5%, 71.4%, 83.9%, and 78.5%, respectively. Tumor relapse occurred in 13 patients (14.9%). Dose escalation to > 63 Gy (maximum 66.6 Gy) to the primary tumor in 38/87 patients revealed a nonsignificant trend for improved 3‑year CFS (82.4% vs. 97%, P = 0.092), a significantly improved CFS for T2/T3 tumors (72.6% vs. 100%, P = 0.008), and a significantly improved 3‑year PFS for T1/T2 tumors (76.7% vs. 100%, P = 0.035). While acute toxicities did not differ, dose escalation > 63 Gy led to a higher rate of chronic skin toxicities (43.8% vs. 69%, P = 0.042). Treatment with intensity-modulated radiotherapy (IMRT) showed a significant improvement in 3‑year OS (75.4% vs. 53.8%, P = 0.048). In multivariate analysis, significant improvements for T1/T2 tumors (CFS, OS, LRC, PFS), G1/2 tumors (PFS), and IMRT (OS) were shown. The nonsignificant trend for CFS improvement with dose escalation > 63 Gy was also apparent in multivariate analysis (P = 0.067).
CONCLUSION
Dose escalation > 63 Gy (maximum 66.6 Gy) may improve CFS and PFS for certain subgroups, with a concomitant increase in chronic skin toxicities. Modern IMRT seems to be associated with an improvement in OS.
Topics: Humans; Neoplasm Recurrence, Local; Treatment Outcome; Radiotherapy, Intensity-Modulated; Chemoradiotherapy; Carcinoma, Squamous Cell; Anus Neoplasms; Epithelial Cells; Retrospective Studies
PubMed: 36862155
DOI: 10.1007/s00066-023-02056-y -
Clinical Infectious Diseases : An... Aug 2023Men who have sex with men (MSM) without HIV are known to be at elevated relative risk for Human papillomavirus (HPV)-associated anal cancer in comparison to men who have...
BACKGROUND
Men who have sex with men (MSM) without HIV are known to be at elevated relative risk for Human papillomavirus (HPV)-associated anal cancer in comparison to men who have sex with women (MSW), but are poorly characterized in terms of anal cancer incidence due to absence of reporting of sexual behavior/identity at a population-level.
METHODS
By combining age-specific statistics from multiple data sources (anal cancer incidence among all males; anal cancer incidence among MSM and MSW with HIV; population size of men with HIV by sexual orientation), we developed a mathematical model to estimate anal cancer incidence, annual number of cases, and proportion by (a) sexual orientation (MSM versus MSW), (b) HIV status, and (c) age (<30, 30-44, 45-59, and ≥60 years).
RESULTS
Anal cancer incidence (per 100 000) among MSM without HIV was 1.4 (95% uncertainty interval [UI], 0.6 to 2.3), 17.6 (95% UI = 13.8-23.5), and 33.9 (95% UI = 28.3-42.3), at ages 30-44, 45-59 and ≥60 years, respectively. 19.1% of all male anal cancer occurred in MSM without HIV, increasing from 4% of anal cancer diagnosed at 30-44 years to 24% at ≥60 years; 54.3% occurred in MSW without HIV (increasing from 13% at age 30-44 to 67% at >60 years), and the remaining 26.6% in men (MSM and MSW combined) with HIV (decreasing from 83% at age 30-44 to 9% at >60 years).
CONCLUSIONS
These findings should inform anal cancer prevention recommendations in male risk groups, including, for the first time, for the important group of MSM without HIV.
Topics: Male; Humans; Female; Adult; Middle Aged; Homosexuality, Male; Human Papillomavirus Viruses; HIV Infections; Incidence; Anus Diseases; Risk Factors; Papillomavirus Infections; Sexual and Gender Minorities; Sexual Behavior; Anus Neoplasms; Anal Canal; HIV; Papillomaviridae
PubMed: 37017078
DOI: 10.1093/cid/ciad205 -
Annals of Palliative Medicine Nov 2023Colorectal (CRC) and anal (AC) cancer, both lower gastrointestinal (GI) cancers vary in their presentation and treatment. Overall, the incidence of CRC has decreased.... (Review)
Review
Colorectal (CRC) and anal (AC) cancer, both lower gastrointestinal (GI) cancers vary in their presentation and treatment. Overall, the incidence of CRC has decreased. However, the incidence of CRCs in younger adults has increased over the last 5 years. The incidence of ACs has increased, too. Women are disproportionally impacted by AC which is frequently associated with human papilloma virus (HPV). Patients diagnosed with both cancers often experience multiple symptoms including pain, constipation, nausea, and vomiting. Psychosocial distress including embarrassment and shame often results from both the cancers itself as well as surgical procedures such as creation of ostomy. Palliative care (PC) is an emerging specialty that focuses on maximizing the quality of life (QOL) for patients through expert symptom assessment and management, psychosocial support, and improved communication around illness. The evidence to support earlier integration of PC has steadily increased over the last ten years. The literature shows that early involvement of PC for these populations can result in improved QOL, improved symptom control and decreased intensity of care at the end of life. This article will review the palliative needs of patients diagnosed with CRC and discuss how PC as a specialty is well poised to support these needs.
Topics: Adult; Humans; Female; Palliative Care; Quality of Life; Gastrointestinal Neoplasms; Anus Neoplasms; Pain
PubMed: 37731305
DOI: 10.21037/apm-22-1390 -
Tomography (Ann Arbor, Mich.) Sep 2023Anal cancer is a rare disease, but its incidence has been increasing steadily. Primary staging and assessment after chemoradiation therapy are commonly performed using... (Review)
Review
UNLABELLED
Anal cancer is a rare disease, but its incidence has been increasing steadily. Primary staging and assessment after chemoradiation therapy are commonly performed using MRI, which is considered to be the preferred imaging modality. CT and PET/CT are useful in evaluating lymph node metastases and distant metastatic disease. Anal squamous-cell carcinoma (ASCC) and rectal adenocarcinoma are typically indistinguishable on MRI, and a biopsy prior to imaging is necessary to accurately stage the tumor and determine the treatment approach. This review discusses the histology, MR technique, diagnosis, staging, and treatment of anal cancer, with a particular focus on the differences in TNM staging between anal and rectal carcinomas.
PURPOSE
This review discusses the histology, MR technique, diagnosis, staging, and treatment of anal cancer, with a particular focus on the differences in TNM staging between anal squamous-cell carcinoma (ASCC) and rectal adenocarcinoma.
METHODS AND MATERIALS
To conduct this updated review, a comprehensive literature search was performed using prominent medical databases, including PubMed and Embase. The search was limited to articles published within the last 10 years (2013-2023) to ensure their relevance to the current state of knowledge.
INCLUSION CRITERIA
(1) articles that provided substantial information on the diagnostic techniques used for ASCC, mainly focusing on imaging, were included; (2) studies reporting on emerging technologies; (3) English-language articles.
EXCLUSION CRITERIA
articles that did not meet the inclusion criteria, case reports, or articles with insufficient data. The primary outcome of this review is to assess the accuracy and efficacy of different diagnostic modalities, including CT, MRI, and PET, in diagnosing ASCC. The secondary outcomes are as follows: (1) to identify any advancements or innovations in diagnostic techniques for ASCC over the past decade; (2) to highlight the challenges and limitations of the diagnostic process.
RESULTS
ASCC is a rare disease; however, its incidence has been steadily increasing. Primary staging and assessment after chemoradiation therapy are commonly performed using MRI, which is considered to be the preferred imaging modality. CT and PET/CT are useful in evaluating lymph node metastases and distant metastatic disease.
CONCLUSION
ASCC and rectal adenocarcinoma are the most common histological subtypes and are typically indistinguishable on MRI; therefore, a biopsy prior to imaging is necessary to stage the tumor accurately and determine the treatment approach.
Topics: Humans; Lymphatic Metastasis; Positron Emission Tomography Computed Tomography; Rare Diseases; Anus Neoplasms; Rectal Neoplasms; Carcinoma, Squamous Cell; Adenocarcinoma
PubMed: 37736988
DOI: 10.3390/tomography9050135