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English KJ. Anal carcinoma - exploring the epidemiology, risk factors, pathophysiology, diagnosis, and treatment. World J Exp Med 2024; 14:98525. [PMID: 39312693 PMCID: PMC11372733 DOI: 10.5493/wjem.v14.i3.98525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 07/15/2024] [Accepted: 08/06/2024] [Indexed: 08/29/2024] Open
Abstract
Anal carcinoma is a relatively rare tumor that accounts for approximately 2% of gastrointestinal malignancies and less than 7% of anorectal cancers. Most anal tumors originate between the anorectal junction and the anal verge. Risk factors for the disease include human papillomavirus infection, human immunodeficiency virus, tobacco use, immunosuppression, female sex, and older age. The pathogenesis of anal carcinoma is believed to be linked to human papillomavirus-related inflammation, leading to dysplasia and progression to cancer. Squamous cell carcinoma is the most common type of anal tumor, with an annual incidence of approximately 1 to 2 per 100000 persons. Treatment regarding anal cancer has emerged over time. However, chemoradiation therapy remains the mainstay approach for early localized disease. Patients with metastatic disease are treated with systemic therapy, and salvage surgery is reserved for disease recurrence following chemoradiation. This article aims to provide background information on the epidemiology, risk factors, pathology, diagnosis, and current trends in the management of anal cancer. Future directions are briefly discussed.
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Affiliation(s)
- Kevan J English
- Department of Medicine, Division of Gastroenterology & Hepatology, Saint George’s University School of Medicine, Saint George 33334, Saint George, Grenada
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Atarere J, Chido-Amajuoyi O, Onyeaka H, Akpoviroro O, Adewunmi C, Mele AA, Faith CO, Nwani S, Kanth P. Awareness of the causal association between human papillomavirus and anal cancer among US adults. Cancer Causes Control 2024; 35:719-725. [PMID: 38103133 DOI: 10.1007/s10552-023-01830-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 11/11/2023] [Indexed: 12/17/2023]
Abstract
PURPOSE The incidence of anal cancer is on the rise in the US, especially among high-risk groups. This study examined the prevalence and determinants of awareness of the causal relationship between HPV and anal cancer among US adults. METHODS Study data was obtained from the 2017 to 2020 iterations of the Health Information National Trends Survey. The prevalence of awareness that HPV causes anal cancer was estimated among HINTS respondents who were aware of HPV in general. Survey weights were used to provide estimates representative of the adult US population. Multivariable logistic regressions were used to examine the associations between awareness that HPV causes anal cancer and cancer-related behaviors/perceptions and sociodemographic characteristics of respondents. RESULTS Two thousand six hundred and eighty four (27.2%) of the study population were aware that HPV caused anal cancer. Those of gay sexual orientation were more aware than heterosexuals [OR 2.27; 95% CI (1.24, 4.14)]. Compared to respondents with a high school diploma or less, individuals with some college education [OR 1.38; 95% CI (1.03, 1.85)] and those with at least a college degree [OR 1.52; 95% CI (1.17, 1.98)] were more likely to be aware. Participants who had positive cancer information seeking behavior were more aware of the HPV-anal cancer link compared to those who did not [OR 1.57; 95% CI (1.30, 1.89)]. CONCLUSION Population-level awareness that HPV causes anal cancer remains critically low in the US. Sexual orientation, level of education and cancer information seeking behavior are associated with increased awareness of the causal relationship between HPV and anal cancer. Efforts should be directed toward addressing the awareness gap among individuals with lower education levels and promoting curiosity-driven information seeking behaviors.
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Affiliation(s)
- Joseph Atarere
- Department of Medicine, MedStar Health, Baltimore, MD, USA.
| | | | - Henry Onyeaka
- Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
| | | | - Comfort Adewunmi
- Division of Geriatrics and Gerontology, Emory University School of Medicine, Atlanta, GA, USA
| | | | - Chilota O Faith
- Department of Medical and Laboratory Sciences, Madonna University, Okija, Anambra State, Nigeria
| | - Somtochi Nwani
- Department of Pharmaceutical Sciences, University of Nigeria, Enugu, Nigeria
| | - Priyanka Kanth
- Division of Gastroenterology, Georgetown University, District of Columbia, Washington, DC, USA
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Abstract
This chapter provides an overview of anal cancer and contemporary approaches for anal precancer detection, beginning with a discussion of the biology and natural history of anal squamous cell carcinoma, the predominant human papillomavirus -associated histologic subtype of anal cancer. This section is followed by a description of the epidemiology of anal cancer, including trends in incidence and mortality, a discussion of populations with elevated risk for anal cancer and an overview of associated risk factors. The remainder of the chapter provides the most up-to-date evidence on tools and approaches for anal cancer prevention, screening, and early detection; including, the role of human papillomavirus vaccination for primary prevention; anal cytology, high resolution anoscopy and novel biomarkers for secondary prevention; and digital anal-rectal examination for early detection.
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Affiliation(s)
- Camryn M Cohen
- Division of Cancer Epidemiology & Genetics, National Cancer Institute, Rockville, Maryland
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McMahon KR, Gemma N, Clapp M, Sanchez-Montejo P, Dibello J, Laipply E. Relationship between anal cancer recurrence and cigarette smoking. World J Clin Oncol 2023; 14:259-264. [PMID: 37583947 PMCID: PMC10424090 DOI: 10.5306/wjco.v14.i7.259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 05/10/2023] [Accepted: 06/13/2023] [Indexed: 07/19/2023] Open
Abstract
BACKGROUND The incidence of anal cancer has been increasing in the United States. Smoking is a well-established risk factor; however, the impact of smoking on disease re-currence and outcome has not been well studied. The aim of this study was to assess the association between anal cancer recurrence and cigarette smoking. AIM To investigate the relationship between cigarette smoking status and anal cancer treatment outcome. METHODS The cancer registry from a single, community hospital was screened for patients with anal cancer between 2010 and 2021. The following characteristics were gathered from the database: Age; sex; cigarette smoking history; American Joint Committee on Cancer Clinical Stage Group; response to therapy; recurrence; time to recurrence; mortality; time to death; and length of follow-up. Patients were divided into the following groups: Current smokers; former smokers; and never smokers. SPSSv25.0 software (IBM Corp., Armonk, NY, United States) was used for statistical analysis. RESULTS A total of 95 patients from the database met the screening criteria. There were 37 never smokers, 22 former smokers, and 36 current smokers. There was no difference between groups in regards to race or sex. There was no difference in the American Joint Committee on Cancer Clinical Stage Group between groups. The former smokers were significantly older when compared to never smokers and current smokers (66.5 ± 13.17 vs 57.4 ± 7.82 vs 63.7 ± 13.80, P = 0.011). Former smokers and current smokers had a higher recurrence rate compared to never smokers (30.8% and 20.8% compared to zero, P = 0.009). There was not a significant difference in recurrence between former smokers and current smokers. There was no difference in the mortality, non-response rate, or time to death between the groups. CONCLUSION Our data contributes evidence that cigarette smoking status is associated with increased recurrence for patients with anal cancer.
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Affiliation(s)
- Kevin R McMahon
- Department of General Surgery, Summa Health System, Akron, OH 44304, United States
| | - Nicholas Gemma
- Department of General Surgery, Summa Health System, Akron, OH 44304, United States
| | - McKenzie Clapp
- Department of General Surgery, Summa Health System, Akron, OH 44304, United States
| | | | - Joseph Dibello
- Department of General Surgery, Summa Health System, Akron, OH 44304, United States
| | - Erica Laipply
- Department of General Surgery, Summa Health System, Akron, OH 44304, United States
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Cachay ER, Gilbert T, Deiss R, Mathews WC. Shared Decision-Making Concerning Anal Cancer Screening in Persons With Human Immunodeficiency Virus. Clin Infect Dis 2023; 76:582-591. [PMID: 35723270 PMCID: PMC10226749 DOI: 10.1093/cid/ciac491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 05/31/2022] [Accepted: 06/09/2022] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Anal high-grade squamous intraepithelial lesion (aHSIL) is the immediate precursor of anal cancer. Anal cytology is a recommended screening test to identify aHSIL among people with human immunodeficiency virus (HIV; PWH). Heterogeneity of risk for invasive anal cancer among PWH suggests the value of a shared decision-making framework regarding screening. METHODS Using a longitudinal HIV cohort with a comprehensive anal cancer screening program, we estimated the adjusted probabilities of having aHSIL on the first anal cytology. We used logistic regression models with inverse probability weighting to account for differential screening in the cohort and to construct a predicted probability nomogram for aHSIL. Sensitivity analysis was performed to estimate aHSIL prevalence corrected for misclassification bias. RESULTS Of 8139 PWH under care between 2007 and 2020, 4105 (49.8%) underwent at least 1 anal cytology test. First-time cytology aHSIL was present in 502 (12.2%) PWH. The adjusted probability of having aHSIL varied from 5% to 18% depending on patient characteristics. Prespecified factors in the aHSIL prediction model included nadir CD4 cell count, ethnicity, race, age, sex, gender identity, and HIV risk factors. The ability of the model to discriminate cytological aHSIL was modest, with an area under the curve of 0.63 (95% confidence interval, .60-.65). CONCLUSIONS PWH are at increased risk for aHSIL and invasive anal cancer. Risk, however, varies by patient characteristics. Individual risk factor profiles predictive of aHSIL can be modeled and operationalized as nomograms to facilitate shared decision-making conversations concerning anal cancer screening.
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Affiliation(s)
- Edward R Cachay
- Department of Medicine, Owen Clinic, University of California–San Diego, San Diego, California, USA
- Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California–San Diego, San Diego, California, USA
| | - Tari Gilbert
- Department of Medicine, Owen Clinic, University of California–San Diego, San Diego, California, USA
| | - Robert Deiss
- Department of Medicine, Owen Clinic, University of California–San Diego, San Diego, California, USA
- Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California–San Diego, San Diego, California, USA
| | - Wm Christopher Mathews
- Department of Medicine, Owen Clinic, University of California–San Diego, San Diego, California, USA
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Turchan WT, Liauw SL. Chemoradiation for Anal Cancer: Clinical Outcomes and Strategies to Optimize the Therapeutic Ratio According to HPV Status. Semin Radiat Oncol 2021; 31:349-360. [PMID: 34455990 DOI: 10.1016/j.semradonc.2021.02.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
The incidence of anal cancer in the United States has increased in recent years, primarily related to the increasing incidence of HPV-associated anal squamous cell carcinoma, which is estimated to represent 80%-95% of anal cancers. Similar to head and neck cancer, HPV association has been demonstrated to be a strong positive prognostic factor in patients with anal cancer. Encouraging results from a number of studies investigating treatment de-escalation for HPV-associated oropharyngeal cancer support the notion that similar attempts may be feasible in HPV-associated anal cancer; however, the data to support this hypothesis are currently lacking. Studies are needed to determine how, if at all, HPV status should impact the management of patients with anal cancer. This review summarizes the relationship between HPV association and outcomes for patients with anal cancer, and how HPV status may impact the treatment of patients with anal cancer going forward.
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Affiliation(s)
| | - Stanley L Liauw
- Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL.
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McGovern J, Fuller C, Burris K. Anal cancer screening and prevention: a review for dermatologists. J Eur Acad Dermatol Venereol 2021; 35:1622-1627. [PMID: 33797819 DOI: 10.1111/jdv.17263] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 03/22/2021] [Indexed: 12/20/2022]
Abstract
The incidence of and mortality from anal cancer, predominantly squamous cell carcinoma (SCC), have been increasing since the 1980s, during an era when many common malignancies have seen decreases in mortality. Dermatologists may be more likely to see patients at an increased risk for anal SCC, such as those living with HIV, MSM and those presenting for management of anogenital warts, yet there is little guidance in the field on how to manage these patients. We underwent a project to review the evidence surrounding screening and prevention of anal SCC. HPV vaccination, the main preventative measure for anal SCC, is often underutilized and may not be effective for those most at risk. Screening methods currently include high-risk HPV and anal cytology testing, with high-resolution anoscopy (HRA) reserved for biopsy and confirmatory testing. High-risk HPV testing has been associated with high sensitivity for intraepithelial neoplasia, but low specificity in high-risk groups. Recent meta-analyses examining AIN detection using anal cytology estimate a similarly high sensitivity of 74-87%, with a relatively higher specificity (44-66%) for identifying high-grade AIN. HRA is the gold standard for diagnosis, but its accessibility and cost are deterrents from its use as a screening tool. Cervical cancer screening, initially adopted without significant evidence of its impact, has significantly decreased cervical cancer rates. The argument can be made that rates of anal SCC may also benefit from appropriate screening methods, particularly anal cytology. It is prudent for dermatologists to be aware of the methods available to them in the management of at-risk patients, the data supporting them, and the potential benefits of screening in order to counsel patients appropriately and address the increasing burden of disease.
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Affiliation(s)
- J McGovern
- Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA
| | - C Fuller
- Department of Dermatology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - K Burris
- Department of Dermatology, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA
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Fuertes I, Cranston R, de Lazzari E, Rodriguez-Carunchio L, Blanco JL. Response factors associated with electrocautery treatment of intra-anal high-grade squamous intraepithelial lesions in a population of HIV-positive men who have sex with men. Int J STD AIDS 2021; 32:1052-1059. [PMID: 33978536 DOI: 10.1177/09564624211017005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Ablative treatment of anal high-grade squamous intraepithelial lesions (HSIL) reduces the risk of progression to anal squamous cell carcinoma. OBJECTIVES To identify factors that influence the response to treatment of anal HSIL by electrocautery ablation (ECA) in a population of HIV-positive men who have sex with men (MSM). DESIGN Retrospective study of ECA treatment response in a prospectively followed anal dysplasia cohort. HIV-positive MSM diagnosed with anal HSIL were included. Demographic and HIV data were recorded. Response to treatment was assessed by biopsy after at least 18 months of follow-up. RESULTS One hundred and twenty-eight HSILs in 91 men were included in this study. The overall response rate at 18 months was 70.3%. The number of electrocautery sessions required (2 ECA sessions vs 1: adjusted odds ratio [aOR] = 0.36 (95%CI 0.13-1.01); >=3 sessions vs 1: aOR = 0.10 (95%CI 0.04-0.29); p < 0.001]) and the history of previous HPV-related anal pathology (previous anal lesions vs no previous lesions AOR = 2.83 (95%CI 1.14-7.02), p = 0.024) were independently associated with response at 18 months. No serious adverse events were reported. CONCLUSIONS Consideration should be given to alternative therapies in patients with unresolved HSIL after 1 ECA treatment.
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Affiliation(s)
- Irene Fuertes
- Department of Dermatology, 16493Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Ross Cranston
- Department of Infectious Diseases, 16493Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | - Elisa de Lazzari
- Department of Infectious Diseases, 16493Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
| | | | - José L Blanco
- Department of Infectious Diseases, 16493Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
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Lerman J, Hennequin C, Etienney I, Abramowitz L, Goujon G, Gornet JM, Guillerm S, Aparicio T, Valverde A, Cattan P, Quéro L. Impact of tobacco smoking on the patient's outcome after (chemo)radiotherapy for anal cancer. Eur J Cancer 2020; 141:143-151. [PMID: 33137590 DOI: 10.1016/j.ejca.2020.09.039] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 09/06/2020] [Accepted: 09/30/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE Anal squamous cell carcinoma is associated with multiple risk factors, including infection with human papillomavirus and human immunodeficiency virus, immunosuppression, multiple sex partners, receptive anal sex and tobacco smoking. The aim of our study was to identify prognostic factors associated with poor outcomes after radiotherapy for anal cancer. METHODS We analysed retrospectively the medical records of 171 patients treated by (chemo)radiotherapy for non-metastatic anal cancer in our institution from 2000 to 2015. Patients and tumour characteristics, treatments (chemotherapy, radiotherapy [RT] and surgery) and outcomes were reported. Colostomy-free survival (CRF), disease-free survival and overall survival (OS) at 5 years were studied. Univariate and multivariate analyses were performed by logistic regression to determine factors associated with poor progression-free survival (PFS). RESULTS Patients' characteristics were as follows: median age, 62 years (range = 36-89); gender, 45 men (26%) and 126 women (74%); HIV serology, positive: 21 patients (12%); tobacco smoking, 86 patients (50%), among whom 28 patients and 58 patients were current and former smokers, respectively. Tumours were classified as locally limited (T1-2, N0, M0) for 86 patients (50%) and locally advanced (T3-4 or N+, M0) for 85 patients (50%). The median total dose was 64.4 Gy (range = 54-76.6), and 146 patients were treated by concurrent chemoradiotherapy. Factors associated with poor PFS in univariate analysis were as follows: tumour size >4 cm, lymph node involvement, tobacco smoking, no initial surgical excision and anal warts at diagnosis. In multivariate analysis, only tobacco smoking status was significantly associated with poor PFS (hazard ratio = 2.85, 95% confidence interval [1.25-6.50], p = 0.013). Five-year PFS for non-smokers, former smokers and current smokers was 88.1%, 76.7% and 73.8%, respectively (p = 0.038). Tobacco smoking was also associated with poor overall survival (p = 0.03), locoregional relapse-free survival (LRFS; p = 0.05) and CFS (p = 0.02). CONCLUSIONS Tobacco smoking status is associated with poor OS, LRFS, PFS and CFS in patients treated for anal cancer by high RT dose ± chemotherapy.
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Affiliation(s)
- Jacques Lerman
- Saint-Louis Hospital, Radiation Oncology, AP-HP. Nord, Paris, France
| | | | | | - Laurent Abramowitz
- Bichat University Hospital, Proctology, AP-HP. Nord, Paris, France; Ramsay GDS Clinique Blomet, Paris, France
| | - Gael Goujon
- Bichat Hospital, Gastroenterology, AP-HP.Nord, Paris, France
| | - Jean-Marc Gornet
- Saint-Louis Hospital, Gastroenterology, AP-HP.Nord, Paris, France
| | - Sophie Guillerm
- Saint-Louis Hospital, Radiation Oncology, AP-HP. Nord, Paris, France
| | - Thomas Aparicio
- INSERM U1160, University of Paris, Paris, France; Saint-Louis Hospital, Gastroenterology, AP-HP.Nord, Paris, France
| | - Alain Valverde
- Croix Saint Simon Hospital, Digestive Surgery, Paris, France
| | - Pierre Cattan
- INSERM U1160, University of Paris, Paris, France; Saint-Louis Hospital, Digestive Surgery, AP-HP. Nord, Paris, France
| | - Laurent Quéro
- Saint-Louis Hospital, Radiation Oncology, AP-HP. Nord, Paris, France; INSERM U1160, University of Paris, Paris, France.
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Lum C, Prenen H, Body A, Lam M, Segelov E. A 2020 update of anal cancer: the increasing problem in women and expanding treatment landscape. Expert Rev Gastroenterol Hepatol 2020; 14:665-680. [PMID: 32458709 DOI: 10.1080/17474124.2020.1775583] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Anal cancer is a rare malignancy with increasing incidence, notably in women. This disease is highly associated with HPV infection and its incidence and mortality are currently rising. Most patients present with localized disease which has a high survival after definitive treatment with chemoradiation. For patients who develop metastatic disease or present with this de novo, survival is poor. AREAS COVERED This review provides a summary of current literature on anal cancer. With a focus on women, this includes current epidemiological trends, role of HPV, and the current and future treatment landscape, including HPV vaccination and immunotherapy. Screening currently focusses on HIV-positive men, missing most female cases. In curative disease, trials are investigating treatment de-intensification in good prognostic groups. Immunotherapy is showing early promise in the advanced disease setting. EXPERT OPINION Similar to cervical cancer, anal cancer is strongly associated with HPV, and therefore, broader implementation of screening programs may reduce its incidence. HPV vaccination is expected to reduce the development of (pre)malignant anal lesions. The emergence of biomarkers will assist patient treatment selection, allowing optimal balance of treatment efficacy and morbidity. It is hoped that new treatment approaches, including immunotherapy, will improve outcomes. International collaboration is needed.
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Affiliation(s)
- Caroline Lum
- Medical Oncology, Monash Medical Centre , Clayton, Australia
| | - Hans Prenen
- Medical Oncology, Monash Medical Centre , Clayton, Australia.,Oncology Department, University Hospital Antwerp , Antwerp, Belgium
| | - Amy Body
- Medical Oncology, Monash Medical Centre , Clayton, Australia
| | - Marissa Lam
- Medical Oncology, Monash Medical Centre , Clayton, Australia
| | - Eva Segelov
- Medical Oncology, Monash Medical Centre , Clayton, Australia.,School of Clinical Sciences, Monash University , Clayton, Australia
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Wang Y, Tao H, Paxton RJ, Wang J, Mubarik S, Jia Y, Wang W, Yu C. Post-diagnosis smoking and risk of cardiovascular, cancer, and all-cause mortality in survivors of 10 adult cancers: a prospective cohort study. Am J Cancer Res 2019; 9:2493-2514. [PMID: 31815049 PMCID: PMC6895457] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2019] [Accepted: 10/06/2019] [Indexed: 06/10/2023] Open
Abstract
Several studies have examined the relationship between smoking and mortality in cancer survivors. However, few have reported the relationships in several cancer sites (i.e., bladder, non-melanoma skin, uterine, melanoma, and lymphoma), and limited data exist on the dose-response relationship between number of cigarettes smoked per day or duration of smoking cessation and mortality. Cancer survivors (N = 35,093, 61% female, mean age = 47 years old) from the National Health Interview Survey with linked data retrieved from the National Death Index served as our study participants. Cox proportional-hazards models were used to assess associations between smoking status, all-cause, and disease-specific mortality. After a median follow-up of 13 years, 11,066 deaths occurred. Survivors who reported smoking at study entry had a 73%, 75%, 85% higher risk for cardiovascular disease, cancer, and all-cause mortality, respectively when compared to nonsmokers. Former smokers had a 31% and 37% higher risk of all-cause and cancer mortality, respectively when compared to nonsmokers. The observed relationships appeared to differ by the number of cigarettes smoked (i.e., ≥ 10 per day), especially for breast, cervix, lung, prostate, uterine and non-melanoma skin cancer survivors. Those who continued smoking post diagnosis were at greatest risk of all-cause and cancer mortality, but the associations varied substantially by cancer site. These data provide sufficient evidence of the health hazards associated with smoking for cancer survivors and provide further support for public health strategies designed to curb smoking in this vulnerable population.
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Affiliation(s)
- Yafeng Wang
- Department of Epidemiology and Biostatistics, School of Health Sciences, Wuhan UniversityWuhan, China
| | - Huan Tao
- Department of Hematology and Research Laboratory of Hematology, West China Hospital, Sichuan UniversityChengdu, Sichuan, China
| | - Raheem J Paxton
- Department of Community Medicine and Population Health, The University of AlabamaTuscaloosa, AL, United States
| | - Junfeng Wang
- Department of Biomedical Data Sciences, Leiden University Medical Center Einthovenweg 202333ZC, Leiden, The Netherlands
| | - Sumaira Mubarik
- Department of Epidemiology and Biostatistics, School of Health Sciences, Wuhan UniversityWuhan, China
| | - Yongqian Jia
- Department of Hematology and Research Laboratory of Hematology, West China Hospital, Sichuan UniversityChengdu, Sichuan, China
| | - Wei Wang
- School of Mathematical Sciences, Shanghai Jiao Tong UniversityShanghai 200240, China
| | - Chuanhua Yu
- Department of Epidemiology and Biostatistics, School of Health Sciences, Wuhan UniversityWuhan, China
- Global Health Institute, Wuhan UniversityWuhan, China
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Kleckner AS, Kleckner IR, Kamen CS, Tejani MA, Janelsins MC, Morrow GR, Peppone LJ. Opportunities for cannabis in supportive care in cancer. Ther Adv Med Oncol 2019; 11:1758835919866362. [PMID: 31413731 PMCID: PMC6676264 DOI: 10.1177/1758835919866362] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 07/03/2019] [Indexed: 12/17/2022] Open
Abstract
Cannabis has the potential to modulate some of the most common and debilitating symptoms of cancer and its treatments, including nausea and vomiting, loss of appetite, and pain. However, the dearth of scientific evidence for the effectiveness of cannabis in treating these symptoms in patients with cancer poses a challenge to clinicians in discussing this option with their patients. A review was performed using keywords related to cannabis and important symptoms of cancer and its treatments. Literature was qualitatively reviewed from preclinical models to clinical trials in the fields of cancer, human immunodeficiency virus (HIV), multiple sclerosis, inflammatory bowel disease, post-traumatic stress disorder (PTSD), and others, to prudently inform the use of cannabis in supportive and palliative care in cancer. There is a reasonable amount of evidence to consider cannabis for nausea and vomiting, loss of appetite, and pain as a supplement to first-line treatments. There is promising evidence to treat chemotherapy-induced peripheral neuropathy, gastrointestinal distress, and sleep disorders, but the literature is thus far too limited to recommend cannabis for these symptoms. Scant, yet more controversial, evidence exists in regard to cannabis for cancer- and treatment-related cognitive impairment, anxiety, depression, and fatigue. Adverse effects of cannabis are documented but tend to be mild. Cannabis has multifaceted potential bioactive benefits that appear to outweigh its risks in many situations. Further research is required to elucidate its mechanisms of action and efficacy and to optimize cannabis preparations and doses for specific populations affected by cancer.
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Affiliation(s)
- Amber S Kleckner
- Cancer Control and Survivorship, University of Rochester Medical Center, CU 420658, 265 Crittenden Blvd., Rochester, NY 14642, USA
| | - Ian R Kleckner
- Cancer Control and Survivorship, University of Rochester Medical Center, Rochester, NY, USA
| | - Charles S Kamen
- Cancer Control and Survivorship, University of Rochester Medical Center, Rochester, NY, USA
| | - Mohamedtaki A Tejani
- Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
| | - Michelle C Janelsins
- Cancer Control and Survivorship, University of Rochester Medical Center, Rochester, NY, USA
| | - Gary R Morrow
- Cancer Control and Survivorship, University of Rochester Medical Center, Rochester, NY, USA
| | - Luke J Peppone
- Cancer Control and Survivorship, University of Rochester Medical Center, Rochester, NY, USA
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Idris S, Baqays A, Isaac A, Chau JKM, Calhoun KH, Seikaly H. The effect of second hand smoke in patients with squamous cell carcinoma of the head and neck. J Otolaryngol Head Neck Surg 2019; 48:33. [PMID: 31337433 PMCID: PMC6652014 DOI: 10.1186/s40463-019-0357-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Accepted: 07/09/2019] [Indexed: 11/11/2022] Open
Abstract
Background Active tobacco smoking is a well-known risk factor for head and neck malignancy, and strong evidence has associated tobacco as the main carcinogenic factor in squamous cell cancers of this region. Evidence supporting a carcinogenic effect of second-hand smoke (SHS) on head and neck organs in non-smokers was also demonstrated with results consistent with those for active smokers. There is little data on the effects of SHS in patients previously treated for squamous cell carcinomas of the head and neck. Objective The purpose of this study was to prospectively evaluate the role of SHS on recurrence and survival in treated head and neck cancer patients. Methods We conducted a prospective cohort study to examine the association between self-reported SHS exposure and the risk of recurrence and mortality in patients treated for squamous cell cancers of the head and neck in a longitudinal fashion. Patients filled out an exhaustive smoking questionnaire on presentation and abbreviated questionnaires at each follow-up visit, which occurred every 6 months. Primary outcome measures were recurrence, development of a second primary malignancy, and recurrence-free survival. Chi square analysis was used to assess the association between SHS and the primary outcomes. A multivariate binary logistic regression analysis was applied to determine the independent predictors of recurrence. Cox proportional hazards and Kaplan Meier modeling were employed to assess the possible relationships between SHS exposure and time to develop the primary outcomes. Results Untreated new patients with a histologically confirmed diagnosis of first primary SCC of the UADT (defined as cancer of the oral cavity, the oropharynx, the hypopharynx, and the larynx) were recruited. Patients seen at The University of Texas Medical Branch (UTMB) Head and Neck oncology clinic from 1988 to 1996 were considered as cases in this study. One hundred and thirty-five patients were enrolled in the study. The median follow-up time for the sample was 54 months (3.92 years). Complete records were achieved for 92% of patients, thus 124 patients were included in the final analysis. SHS significantly correlated with recurrence and recurrence-free survival. The rate of recurrence was 46% in the group exposed to SHS and 22% in the non-exposed group. Based on multivariate binary logistic regression analysis, SHS exposure was detected as a significant independent predictor for recurrence (HR = 3.00 [95% CI 1.18–7.63]). Kaplan-Meier analysis demonstrated that patients who were not exposed to SHS had a statistically significant longer recurrence-free survival (log-rank P = 0.029). The mean survival for non SHS-exposed patients was 76 [63–89] months versus 54 [45–63] months for those exposed to SHS. Conclusions SHS exposure is an independent predictor of recurrence and survival after head and neck cancer treatment. These results support the importance and efforts of reducing smoking at home in in the work-place.
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Affiliation(s)
- Sherif Idris
- Division of Otolaryngology - Head & Neck Surgery, Department of Surgery, University of Alberta Hospital, 1E4.34 Walter C. Mackenzie Centre, Edmonton, Alberta, T6G 2B7, Canada
| | - Abdulsalam Baqays
- Division of Otolaryngology - Head & Neck Surgery, Department of Surgery, University of Alberta Hospital, 1E4.34 Walter C. Mackenzie Centre, Edmonton, Alberta, T6G 2B7, Canada
| | - André Isaac
- Division of Otolaryngology - Head & Neck Surgery, Department of Surgery, University of Alberta Hospital, 1E4.34 Walter C. Mackenzie Centre, Edmonton, Alberta, T6G 2B7, Canada
| | - Jason K M Chau
- Division of Otolaryngology - Head & Neck Surgery, Department of Surgery, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
| | - Karen H Calhoun
- Department of Otolaryngology - Head & Neck Surgery, Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Hadi Seikaly
- Division of Otolaryngology - Head & Neck Surgery, Department of Surgery, University of Alberta Hospital, 1E4.34 Walter C. Mackenzie Centre, Edmonton, Alberta, T6G 2B7, Canada.
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Ashktorab H, Kupfer SS, Brim H, Carethers JM. Racial Disparity in Gastrointestinal Cancer Risk. Gastroenterology 2017; 153:910-923. [PMID: 28807841 PMCID: PMC5623134 DOI: 10.1053/j.gastro.2017.08.018] [Citation(s) in RCA: 190] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2017] [Revised: 07/25/2017] [Accepted: 08/05/2017] [Indexed: 12/13/2022]
Abstract
Cancer from the gastrointestinal tract and its associated excretory organs will occur in more than 300,000 Americans in 2017, with colorectal cancer responsible for >40% of that burden; there will be more than 150,000 deaths from this group of cancers in the same time period. Disparities among subgroups related to the incidence and mortality of these cancers exist. The epidemiology and risk factors associated with each cancer bear out differences for racial groups in the United States. Esophageal adenocarcinoma is more frequent in non-Hispanic whites, whereas esophageal squamous cell carcinoma with risk factors of tobacco and alcohol is more frequent among blacks. Liver cancer has been most frequent among Asian/Pacific Islanders, chiefly due to hepatitis B vertical transmission, but other racial groups show increasing rates due to hepatitis C and emergence of cirrhosis from non-alcoholic fatty liver disease. Gastric cancer incidence remains highest among Asian/Pacific Islanders likely due to gene-environment interaction. In addition to esophageal squamous cell carcinoma, cancers of the small bowel, pancreas, and colorectum show the highest rates among blacks, where the explanations for the disparity are not as obvious and are likely multifactorial, including socioeconomic and health care access, treatment, and prevention (vaccination and screening) differences, dietary and composition of the gut microbiome, as well as biologic and genetic influences. Cognizance of these disparities in gastrointestinal cancer risk, as well as approaches that apply precision medicine methods to populations with the increased risk, may reduce the observed disparities for digestive cancers.
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Affiliation(s)
- Hassan Ashktorab
- Department of Medicine, Howard University, Washington, District of Columbia; Cancer Center, Howard University, Washington, District of Columbia
| | - Sonia S Kupfer
- Section of Gastroenterology, Department of Medicine, University of Chicago, Chicago, Illinois
| | - Hassan Brim
- Department of Pathology, Howard University, Washington, District of Columbia
| | - John M Carethers
- Division of Gastroenterology, Department of Internal Medicine, Department of Human Genetics and Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan.
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15
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Geh I, Gollins S, Renehan A, Scholefield J, Goh V, Prezzi D, Moran B, Bower M, Alfa-Wali M, Adams R. Association of Coloproctology of Great Britain & Ireland (ACPGBI): Guidelines for the Management of Cancer of the Colon, Rectum and Anus (2017) - Anal Cancer. Colorectal Dis 2017; 19 Suppl 1:82-97. [PMID: 28632308 DOI: 10.1111/codi.13709] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Ian Geh
- Queen Elizabeth Hospital, Birmingham, UK
| | | | - Andrew Renehan
- University of Manchester and Christie Hospital, Manchester, UK
| | - John Scholefield
- University of Nottingham and Queens Medical Centre, Nottingham, UK
| | - Vicky Goh
- King's College and Guy's & St Thomas' Hospital, London, UK
| | | | - Brendan Moran
- Basingstoke & North Hampshire Hospital, Basingstoke, UK
| | - Mark Bower
- Imperial College and Chelsea & Westminster Hospital, London, UK
| | | | - Richard Adams
- Cardiff University and Velindre Cancer Centre, Cardiff, UK
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16
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Singh MP, Kaur M, Gupta N, Kumar A, Goyal K, Sharma A, Majumdar M, Gupta M, Ratho RK. Prevalence of high-risk human papilloma virus types and cervical smear abnormalities in female sex workers in Chandigarh, India. Indian J Med Microbiol 2017; 34:328-34. [PMID: 27514955 DOI: 10.4103/0255-0857.188325] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
PURPOSE Cervical cancer is the most common cancer among women in developing nations. Nearly 90% of the cases have been linked to the presence of high-risk human papillomavirus (hrHPV) types 16 and 18. The risk of cervical cancer may be high in female sex workers (FSWs) due to multiple sexual partners. This study aimed to determine the prevalence of cytological abnormalities and hrHPV types 16 and 18 in FSWs in Chandigarh, North India using the liquid-based cytology (LBC) approach. MATERIALS AND METHODS The cervical brush samples were collected from 120 FSW and 98 age-matched healthy controls (HCs). These were subjected to pap smear using conventional method, LBC and the detection of hrHPV types 16 and 18 was carried out using polymerase chain reaction. RESULTS The LBC samples showed better cytological details and also reduced the number of unsatisfactory smears from 11% in Pap to 1.5% in the LBC. A significantly higher number of inflammatory smears were reported in FSWs (51.7% vs. 34.7%, P = 0.01). The hrHPV types 16/18 were detected in 33/120 (27.5%) FSW versus 23/98 (23.5%) HCs. The risk of acquiring hrHPV was higher in FSWs, who had age at first sex ≤25 years, higher income and the habit of smoking. CONCLUSION The high prevalence of hrHPV among FSWs and HCs suggests the need for the implementation of effective National Screening Programme for early detection of hrHPV types to decrease the burden of cervical cancer, especially in high-risk population.
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Affiliation(s)
- M P Singh
- Department of Virology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - M Kaur
- School of Public, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - N Gupta
- Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - A Kumar
- Department of Virology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - K Goyal
- Department of Virology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - A Sharma
- Department of Virology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - M Majumdar
- Department of Virology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - M Gupta
- School of Public, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - R K Ratho
- Department of Virology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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17
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Grahn SW, Kwaan MR, Madoff RD. Malignant Conditions Including Squamous Cell Carcinoma and Rare Cancers. ANUS 2014:71-90. [DOI: 10.1007/978-1-84882-091-3_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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18
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Smyth EC, Capanu M, Janjigian YY, Kelsen DK, Coit D, Strong VE, Shah MA. Tobacco use is associated with increased recurrence and death from gastric cancer. Ann Surg Oncol 2012; 19:2088-94. [PMID: 22395977 DOI: 10.1245/s10434-012-2230-9] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2011] [Indexed: 12/13/2022]
Abstract
BACKGROUND Tobacco use increases the risk of developing gastric cancer. We examined the hypothesis that gastric cancer developing in patients with a history of tobacco use may be associated with increased risk of cancer-specific death after curative surgical resection. METHODS From the Memorial Sloan-Kettering Cancer Center Gastric Cancer prospective surgical database, we collected baseline demographic data and tumor characteristics from all patients who had undergone curative resection for gastric cancer between 1995 and 2009 and who had not received pre- or postoperative chemo- or radiotherapy. A smoking history was defined as >100 cigarettes' lifetime use. The primary end point was gastric cancer disease-specific survival (DSS); secondary end points were 5-year disease-free survival (DFS) and overall survival (OS). Gastric cancer-specific hazard was modeled by Cox regression. RESULTS A total of 699 eligible patients were identified with a median age of 70 years (range 25-96 years); 410 (59%) were current or previous smokers. Smoking was associated with gastroesophageal junction/cardia tumors and white non-Hispanic ethnicity. Multivariate analysis included the following variables: tumor stage, age, performance status, diabetes mellitus, gender, and tumor location. In this analysis, the hazard ratio for gastric cancer DSS in smokers was 1.43 (95% confidence interval 1.08-1.91, P=0.01). Smoking was also an independent significant risk factor for worse 5-year DFS (hazard ratio 1.46, P=0.007) and OS (hazard ratio 1.48, P=0.003). Among 516 patients for whom tobacco pack-year usage was available, both heavy (≥20 pack-years) and light (<20 pack-years) tobacco use was significantly associated with DSS, DFS, and OS. CONCLUSIONS Smoking history appears to be an independent risk factor for death from gastric cancer in patients who have undergone curative surgical resection.
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Affiliation(s)
- E C Smyth
- Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
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19
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Moon IJ, Lee DY, Suh MW, Han DH, Kim ST, Min YG, Lee CH, Rhee CS. Cigarette smoking increases risk of recurrence for sinonasal inverted papilloma. Am J Rhinol Allergy 2011; 24:325-9. [PMID: 21244731 DOI: 10.2500/ajra.2010.24.3510] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Sinonasal inverted papilloma (IP) is a neoplasm in the nasal cavity, characterized by its local aggressiveness and tendency to cause malignancy. Despite the frequent recurrence of IP, few studies have reported the effects of situational parameters including smoking on the recurrence rate of IP. This study was performed to evaluate clinical and environmental factors including smoking that can predict neoplasm recurrence after surgery in patients with IP. METHODS This study was conducted retrospectively on 132 patients who were diagnosed with IP between November 1985 and September 2007. The study focused on the risk factors of recurrence, such as smoking behaviors, diabetes mellitus (DM), hypertension (HTN), allergic rhinitis (AR), the sites of tumor origin and involvement, neoplasm staging, and the surgical method. The age of the patients ranged from 22 to 85 years, and among the 132 patients, 39 patients were smokers (29.5%), 17 (13.3%) with DM, 31 (24.4%) with HTN, and 11 (9.3%) with AR. RESULTS The recurrence rate showed great disparity between the groups of smokers and nonsmokers: 28.2% of smokers suffered recurrence compared with 10.7% recurrence from the nonsmoker group. The Krouse stage IV group experienced more frequent recurrence than the stage I, II, and III groups. Some patients in Krouse stage III (5/72, 6.9%) and IV (3/3, 100%) groups underwent malignant transformation of IP. Histories of DM, HTN, and AR did not exert a statistically meaningful influence on the recurrence and malignant transformation. CONCLUSION The smoking behavior and tumor with extranasal/sinus extension appear to be associated with recurrence of IP after surgical resection.
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Affiliation(s)
- Il Joon Moon
- Department of Otorhinolaryngology, Seoul National University College of Medicine, Seoul, Korea
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20
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Ramamoorthy S, Devaraj B, Miyai K, Luo L, Liu YT, Boland CR, Goel A, Carethers JM. John Cunningham virus T-antigen expression in anal carcinoma. Cancer 2010; 117:2379-85. [PMID: 24048785 DOI: 10.1002/cncr.25793] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2010] [Revised: 10/07/2010] [Accepted: 10/11/2010] [Indexed: 12/29/2022]
Abstract
BACKGROUND Anal carcinoma is thought to be driven by human papillomavirus (HPV) infection through interrupting function of cell regulatory proteins such as p53 and pRb. John Cunningham virus (JCV) expresses a T-antigen that causes malignant transformation through development of aneuploidy and interaction with some of the same regulatory proteins as HPV. JCV T-antigen is present in brain, gastric, and colon malignancies, but has not been evaluated in anal cancers. The authors examined a cohort of anal cancers for JCV T-antigen and correlated this with clinicopathologic data. METHODS Archived anal carcinomas were analyzed for JCV T-antigen expression. DNA from tumor and normal tissue was sequenced for JCV with viral copies determined by quantitative polymerase chain reaction and Southern blotting. HPV and microsatellite instability (MSI) status was correlated with JCV T-antigen expression. RESULTS Of 21 cases of anal cancer (mean age 49 years, 38% female), 12 (57%) were in human immunodeficiency virus (HIV)-positive individuals. All 21 cancers expressed JCV T-antigen, including 9 HPV-negative specimens. More JCV copies were present in cancer versus surrounding normal tissue (mean 32.54 copies/μg DNA vs 2.98 copies/μg DNA, P = .0267). There was no correlation between disease stage and viral copies, nor between viral copies and HIV-positive or -negative status (28.7 vs 36.34 copies/μg DNA, respectively, P = .7804). In subset analysis, no association was found between JCV T-antigen expression and HPV or MSI status. CONCLUSIONS Anal carcinomas uniformly express JCV T-antigen and contain more viral copies compared with surrounding normal tissue. JCV and its T-antigen oncogenic protein, presumably through interruption of cell regulatory proteins, may play a role in anal cancer pathogenesis.
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Affiliation(s)
- Sonia Ramamoorthy
- Department of Surgery, University of California, San Diego, California; Moores Comprehensive Cancer Center, University of California, San Diego, California
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21
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Ramamoorthy S, Liu YT, Luo L, Miyai K, Lu Q, Carethers JM. Detection of multiple human papillomavirus genotypes in anal carcinoma. Infect Agent Cancer 2010; 5:17. [PMID: 20939896 PMCID: PMC2964599 DOI: 10.1186/1750-9378-5-17] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2010] [Accepted: 10/12/2010] [Indexed: 12/31/2022] Open
Abstract
UNLABELLED Infection with human papillomavirus (HPV) is a major risk factor for development of anal squamous cell carcinoma. Despite over 100 genotypes of the virus, HPV 16 and 18 are considered pathogenic as they are seen in the majority of cervical and anal cancers. We have employed a custom microarray to examine DNA for several HPV genotypes. We aimed to determine the accuracy of our microarray in anal cancer DNA for HPV genotypes compared to the DNA sequencing gold standard. METHODS We utilized a sensitive microarray platform to classify 37 types of mucosal HPVs including 14 known high-risk and 23 low-risk types based on cervical cancer data. We utilized DNA from pathologically confirmed cases of anal squamous cell carcinoma. All samples underwent microarray HPV genotyping and PCR analysis. RESULTS HPV was detected in 18/20 (90%) anal cancers. HPV genotypes 16 and 18 were present in the majority of specimens, with HPV 16 being the most common. Eighty percent of anal cancers had at least two HPV types. Ten percent of cases (2/20) tested negative using our microarray; DNA sequencing confirmed the lack of presence of HPV DNA in these samples. CONCLUSIONS Microarray technology is an accurate way to screen for various genotypes of HPV in anal cancer, with 100% correlation with genomic DNA detection of HPV. The majority of anal cancers in our study associated with pathogenic HPV 16 and/or 18. Other HPV genotypes are present simultaneously with HPV 16 and 18, and might contribute to its pathogenesis.
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Affiliation(s)
- Sonia Ramamoorthy
- Departments of Surgery, University of California, 9500 Gilman Drive, San Diego, California, 92093-0068, USA.
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Kreuter A, Potthoff A, Brockmeyer NH, Gambichler T, Swoboda J, Stücker M, Schmitt M, Pfister H, Wieland U. Anal carcinoma in human immunodeficiency virus-positive men: results of a prospective study from Germany. Br J Dermatol 2010; 162:1269-77. [PMID: 20184584 DOI: 10.1111/j.1365-2133.2010.09712.x] [Citation(s) in RCA: 123] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Anal intraepithelial neoplasia (AIN), a human papillomavirus (HPV)-associated potential precursor lesion of anal cancer, is frequent among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). There is a paucity of data published on the progression of high-grade AIN to invasive cancer as well as on clinical and virological characteristics comparing anal margin and anal canal carcinoma. OBJECTIVES To search for anal carcinoma and AIN in a large series of HIV-positive MSM, to assess treatment response of anal carcinoma, and to analyse lesional HPV spectrum of anal cancers. METHODS Detection of anal carcinoma and AIN was performed using cytology, high-resolution anoscopy, and histology in case of abnormal findings. Additionally, HPV analyses for 36 high- and low-risk α-HPV types were performed in patients with anal carcinoma. RESULTS In total, 446 German HIV-positive MSM were examined within an observation period of 5 years and 10 months. Of these, 116 (26·0%) patients had normal findings, 163 (36·5%) had low-grade AIN, 156 (35·0%) had high-grade AIN, and 11 (2·5%) had anal carcinoma as evidenced by the highest grade of cytology/histology. Five patients with anal cancer, who had refused treatment of their precancerous lesions, had progressed from high-grade AIN to invasive cancer within a median time of 8·6 months. All anal cancers carried high-risk α-HPV types. All five squamous cell carcinomas (SCCs) of the anal canal were HPV16 positive. In contrast, only one of the four anal margin SCCs were HPV16 positive (HPV31, HPV33 and HPV33 + HPV68 were found in the other three anal margin SCCs). HPV59 was found in two adenocarcinomas, one of which additionally carried HPV33. In contrast to the cancer biopsies, a broad spectrum of surface high- and low-risk HPV types was found in anal swabs of the patients. Surgical excision resulted in long-term disease control of all anal margin carcinomas, whereas combined chemoradiotherapy in carcinomas of the anal canal was associated with high recurrence rates, high toxicity, and high mortality. CONCLUSIONS Anal carcinoma and AIN are frequent in HIV-positive men, even in patients participating in anal cancer prevention programmes. High-grade dysplasia in these patients can progress to invasive cancer within a short period of time. Anal margin carcinoma and anal canal carcinoma differ substantially in their lesional HPV spectrum, prognosis and treatment response.
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Affiliation(s)
- A Kreuter
- Department of Dermatology, Ruhr University Bochum, Gudrunstrasse 56, D-44791 Bochum, Germany.
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