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Gerhard R, Colmenarez CR, Selle C, Hammer GP. Digital Cytology Combined With Artificial Intelligence Compared to Conventional Microscopy for Anal Cytology: A Preliminary Study. Cytopathology 2025; 36:250-258. [PMID: 40070157 DOI: 10.1111/cyt.13482] [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: 12/12/2024] [Revised: 01/24/2025] [Accepted: 03/03/2025] [Indexed: 04/11/2025]
Abstract
INTRODUCTION Recent studies have shown that digital cytology (DC) coupled with artificial intelligence (AI) algorithms is a valid approach to the diagnosis of cervico-vaginal lesions using liquid-based cytology (LBC). We evaluated the use of these methods for anal LBC specimens. METHODS A series of 124 anal LBC slides previously diagnosed by conventional microscopy (CC) were reviewed with a DC/AI system that generated a gallery of images. Diagnoses based on the selected images, according to the 2014 Bethesda System for Reporting Cervical Cytology, were compared to CC. RESULTS Overall, CC and DC/AI approaches detected a similar number of abnormal (ASC-US+) cases (63 and 62 cases, respectively). We observed an exact concordance between CC and DC in 70 (57.9%) cases, corresponding to a moderate agreement between the two approaches (κ = 0.41, p < 0.001). A moderate agreement (κ = 0.48, p < 0.001) was also found when positive cases were stratified into 'low-grade' (ASC-US, LSIL) and 'high-grade' lesions (ASC-H, HSIL). The DC/AI system detected more cases of higher severity (ASC-H, HSIL: 9 and 2 cases, respectively) than CC (3 cases classified as HSIL). CONCLUSIONS The number of ASC-US+ cases detected by both systems was similar. The DC/AI system detected more cases of higher severity compared to the CC.
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Affiliation(s)
- Renê Gerhard
- Centre National de Pathologie, Laboratoire National de Santé, Dudelange, Luxembourg
| | | | - Corinne Selle
- Centre National de Pathologie, Laboratoire National de Santé, Dudelange, Luxembourg
| | - Gaël Paul Hammer
- Centre National de Pathologie, Laboratoire National de Santé, Dudelange, Luxembourg
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Liang B, Zhao J, Kim Y, Barry-Holson KQ, Bingham DB, Charville GW, Darragh TM, Folkins AK, Howitt BE, Kong CS, Longacre TA, McHenry AJ, Toland AMS, Zhang X, Lim K, Khan MJ, Kang D, Yang EJ. Scattering-Based Light-Sheet Microscopy Imaging of Human Papillomavirus-Associated Squamous Lesions of the Anal Canal: A Proof-of-Principle Study. Mod Pathol 2024; 37:100493. [PMID: 38615709 PMCID: PMC11193612 DOI: 10.1016/j.modpat.2024.100493] [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: 11/22/2023] [Revised: 03/09/2024] [Accepted: 04/03/2024] [Indexed: 04/16/2024]
Abstract
Demand for anal cancer screening is expected to rise following the recent publication of the Anal Cancer-HSIL Outcomes Research trial, which showed that treatment of high-grade squamous intraepithelial lesions significantly reduces the rate of progression to anal cancer. While screening for human papillomavirus-associated squamous lesions in the cervix is well established and effective, this is less true for other sites in the lower anogenital tract. Current anal cancer screening and prevention rely on high-resolution anoscopy with biopsies. This procedure has a steep learning curve for providers and may cause patient discomfort. Scattering-based light-sheet microscopy (sLSM) is a novel imaging modality with the potential to mitigate these challenges through real-time, microscopic visualization of disease-susceptible tissue. Here, we report a proof-of-principle study that establishes feasibility of dysplasia detection using an sLSM device. We imaged 110 anal biopsy specimens collected prospectively at our institution's dysplasia clinic (including 30 nondysplastic, 40 low-grade squamous intraepithelial lesion, and 40 high-grade squamous intraepithelial lesion specimens) and found that these optical images are highly interpretable and accurately recapitulate histopathologic features traditionally used for the diagnosis of human papillomavirus-associated squamous dysplasia. A reader study to assess diagnostic accuracy suggests that sLSM images are noninferior to hematoxylin and eosin images for the detection of anal dysplasia (sLSM accuracy = 0.87; hematoxylin and eosin accuracy = 0.80; P = .066). Given these results, we believe that sLSM technology holds great potential to enhance the efficacy of anal cancer screening by allowing accurate sampling of diagnostic tissue at the time of anoscopy. While the current imaging study was performed on ex vivo biopsy specimens, we are currently developing a handheld device for in vivo imaging that will provide immediate microscopic guidance to high-resolution anoscopy providers.
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Affiliation(s)
- Brooke Liang
- Department of Pathology, Stanford University School of Medicine, Stanford, California
| | - Jingwei Zhao
- Wyant College of Optical Sciences, University of Arizona, Tucson, Arizona
| | - Yongjun Kim
- Department of Biomedical Engineering, University of Arizona, Tucson, Arizona
| | - Keegan Q Barry-Holson
- Department of Pathology, Stanford University School of Medicine, Stanford, California
| | - David B Bingham
- Department of Pathology, Stanford University School of Medicine, Stanford, California
| | - Gregory W Charville
- Department of Pathology, Stanford University School of Medicine, Stanford, California
| | - Teresa M Darragh
- Department of Pathology, University of California San Francisco, San Francisco, California
| | - Ann K Folkins
- Department of Pathology, Stanford University School of Medicine, Stanford, California
| | - Brooke E Howitt
- Department of Pathology, Stanford University School of Medicine, Stanford, California
| | - Christina S Kong
- Department of Pathology, Stanford University School of Medicine, Stanford, California
| | - Teri A Longacre
- Department of Pathology, Stanford University School of Medicine, Stanford, California
| | - Austin J McHenry
- Department of Pathology, Stanford University School of Medicine, Stanford, California
| | - Angus M S Toland
- Department of Pathology, University of Colorado, Aurora, Colorado
| | - Xiaoming Zhang
- Department of Pathology, Stanford University School of Medicine, Stanford, California
| | - Koeun Lim
- Biotronik Neuro, Lake Oswego, Oregon
| | - Michelle J Khan
- Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California
| | - Dongkyun Kang
- Wyant College of Optical Sciences, University of Arizona, Tucson, Arizona; Department of Biomedical Engineering, University of Arizona, Tucson, Arizona
| | - Eric J Yang
- Department of Pathology, Stanford University School of Medicine, Stanford, California.
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Ramos-Cartagena JM, Keller K, Guiot HM, Muñoz C, Colón-López V, Deshmukh AA, Suárez EL, Tirado-Gómez M, Ortiz AP. Evaluating the performance of anal cytology and high-risk HPV genotyping for detecting anal HSIL in a clinic-based sample of people living with and without HIV in Puerto Rico. Cancer Cytopathol 2023; 131:655-664. [PMID: 37358055 PMCID: PMC10650567 DOI: 10.1002/cncy.22738] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 05/19/2023] [Accepted: 05/22/2023] [Indexed: 06/27/2023]
Abstract
BACKGROUND Given the disproportionately elevated anal cancer risk in high-risk populations, it is important to assess the performance of commonly used anal cancer screening tools to improve the effectiveness of detection and treatment methods. This study evaluates 1) the concordance between anal cytology and histology results and 2) the performance of cytology and high-risk human papillomavirus (HR-HPV) genotyping as screening tools for detecting histologically confirmed anal high-grade squamous intraepithelial lesions (HSIL). METHODS Data from the Anal Neoplasia Clinic in Puerto Rico (2014-2021; n = 466) was used. The clinical performance of anal cytology and HR-HPV genotyping to detect HSIL was compared to the gold standard: high-resolution anoscopy-guided biopsy. Sensitivity, specificity, positive predictive value, negative predictive value, and κ coefficients were calculated. RESULTS A total of 66.95% of the patients were men, 74.0% were people living with HIV, 76.2% had anal HR-HPV infection, and 40.34% had histologically confirmed anal HSIL. The weighted κ statistic between the tests (cytology and histology) was 0.25 (p < .001). The sensitivity and specificity of cytology alone to detect anal HSIL were 84.3% (95% confidence interval [CI], 78.3%-89.1%) and 36.0% (95% CI, 30.3%-42.0%), respectively. Anal HR-HPV genotyping had higher sensitivity (92.2%; 95% CI, 87.4%-95.6%) and similar specificity (34.8%; 95% CI, 29.2%-40.7%) compared to cytology. The two tests combined (positive results following cytology or HR-HPV test) improved sensitivity to detect anal HSIL (97.9%; 95% CI, 94.8%-99.4%), but specificity was compromised (19.2%; 95% CI, 14.7%-24.4%). CONCLUSION Although HR-HPV genotyping improved the detection of anal HSIL, HR-HPV testing had lower specificity than anal cytology alone.
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Affiliation(s)
| | | | - Humberto M. Guiot
- University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto Rico
- School of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico
| | - Cristina Muñoz
- University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto Rico
| | - Vivian Colón-López
- University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto Rico
| | - Ashish A. Deshmukh
- Department of Public Health Sciences, College of Medicine, Medical University of South Carolina, Charleston, South Carolina
- Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina
| | - Erick L. Suárez
- University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto Rico
| | - Maribel Tirado-Gómez
- University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto Rico
- School of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico
| | - Ana Patricia Ortiz
- University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto Rico
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de Barcellos LP, Coutinho JRH, Cytryn A, Russomano FB. Conventional cytologic diagnosis of human papillomavirus-induced anal intraepithelial neoplasia: The experience of a referral center in Rio de Janeiro, Brazil. Diagn Cytopathol 2023; 51:166-173. [PMID: 36398627 DOI: 10.1002/dc.25079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 11/02/2022] [Accepted: 11/03/2022] [Indexed: 11/19/2022]
Abstract
BACKGROUND Screening of anal cancer is rarely available or performed in Brazil. This study analyzes the diagnostic performance of conventional cytology (CC) in the prevention of anal cancer in a coloproctology and gynecology outpatient clinics in a public hospital in Rio de Janeiro, Brazil. METHODS From 2005 to 2017, 1066 conventional cytological samples were collected. We analyze the causes of unsatisfactory samples (11.3%) and compare the cytological diagnoses of 83 samples from persons living with HIV and persons not living with HIV and in specific situations, using as the gold standard high-resolution anoscopy or histopathology in cases biopsied within 6 months after cytology. RESULTS The sensitivity of cytology with diagnosis of ASC-US for detection of anal intraepithelial neoplasia of any grade was 85%, specificity was 41%, positive and negative predictive values were 64% and 75%, respectively, and positive and negative likelihood ratios were 1.46 and 0.35, respectively. CONCLUSION Conventional cytology available in resource-limited settings is a simple, noninvasive, low-cost method that proved feasible for outpatient screening of precursor lesions of the anal canal.
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Affiliation(s)
| | | | - Andrea Cytryn
- Federal Hospital of Ipanema, Ministry of Health, Rio de Janeiro, Brazil
| | - Fabio Bastos Russomano
- Fernandes Figueira Institute of Women's, Child's and Adolescent's Health, Ministry of Health, Rio de Janeiro, Brazil
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Torres M, Silva-Klug A, Ferrer E, Saumoy M, Trenti L, Tous S, Esteban A, Baixeras N, Catala I, Vidal A, G Bravo I, Podzamczer D, de Sanjose S. Detecting anal human papillomavirus infection in men who have sex with men living with HIV: implications of assay variability. Sex Transm Infect 2022; 99:187-190. [PMID: 35545433 PMCID: PMC10176368 DOI: 10.1136/sextrans-2021-055303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 04/15/2022] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND Incidence of anal cancer (AC) caused by persistent human papillomavirus (HPV) infection has risen in the last years in men who have sex with men (MSM) living with HIV. There is consensus that this population should be screened for anal precancerous lesions, but the role of HPV DNA testing in AC screening programmes is still under debate. OBJECTIVES This study employed two molecular test to detect anal HPV DNA and compared assay performance and prognostic value for the diagnosis of histology proven high-grade intraepithelial anal lesions. METHODS MSM living with HIV attended their regular check-up visits consisting of detection of anal HPV infection, anal cytology, digital anorectal examination and high resolution anoscopy. HPV DNA was detected using Hybrid Capture 2 High-Risk test (HC2, total assay) and LINEAR ARRAY HPV Genotyping Test (LA, type-specific assay) RESULTS: Among 274 participant, prevalence of HPV DNA was 48.5% by HC2 and 89.4% by LA. HPV16 (30.6%) and HPV6 (19.6%) were the most common genotypes identified. Prevalence of multiple HPV infections was 56.2%. Agreement between HPV DNA assays was 75.2% (κ=0.51; 95% CI 0.42 to 0.60). Total HPV detection demonstrated high sensitivity (90%; 95% CI 68.3 to 98.8) and moderate specificity (58.4%; 95% CI 50.2 to 66.3), while type-specific HPV16/18 genotyping provided an increase in specificity and showed the highest area under the curve (0.81; 95% CI 0.74 to 0.89) and Youden's index (0.63). CONCLUSIONS Both methodologies identified a high prevalence of anal HPV infection and multiple HPV infections in MSM living with HIV, showing a moderate overall agreement between them. Either total HPV detection or type-specific HPV16/18 detection together with a threshold ≥atypical squamous cells of undetermined significance for abnormal cytology showed an acceptable diagnostic accuracy.
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Affiliation(s)
- Montserrat Torres
- Infection and Cancer Laboratory, Cancer Epidemiology Research Program, Institut Catala d' Oncologia-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
| | - Ana Silva-Klug
- HIV and STD Unit (Infectious Disease Service), Hospital Universitari de Bellvitge-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
| | - Elena Ferrer
- HIV and STD Unit (Infectious Disease Service), Hospital Universitari de Bellvitge-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
| | - Maria Saumoy
- HIV and STD Unit (Infectious Disease Service), Hospital Universitari de Bellvitge-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
| | - Loris Trenti
- General Surgery Department, Hospital Universitari de Bellvitge-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
| | - Sara Tous
- Infection and Cancer Unit. Cancer Epidemiology Research Program, Institut Catala d' Oncologia-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.,CIBERESP, Madrid, Comunidad de Madrid, Spain
| | - Ana Esteban
- Infection and Cancer Laboratory, Cancer Epidemiology Research Program, Institut Catala d' Oncologia-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
| | - Nuria Baixeras
- Pathology Unit, Hospital Universitari de Bellvitge-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Catalunya, Spain
| | - Isabel Catala
- Pathology Unit, Hospital Universitari de Bellvitge-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Catalunya, Spain
| | - August Vidal
- Pathology Unit, Hospital Universitari de Bellvitge-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Catalunya, Spain
| | - Ignacio G Bravo
- Laboratory MIVEGEC (CNRS IRD Univ Montpellier), Centre National de la Recherche Scientifique, Montpellier, France
| | - Daniel Podzamczer
- HIV and STD Unit (Infectious Disease Service), Hospital Universitari de Bellvitge-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
| | - Silvia de Sanjose
- Infection and Cancer Unit. Cancer Epidemiology Research Program, Institut Catala d' Oncologia-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.,CIBERESP, Madrid, Comunidad de Madrid, Spain.,Consultant, National Cancer Institute, Rockville, Maryland, USA
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Barroso LF, Stier EA, Hillman R, Palefsky J. Anal Cancer Screening and Prevention: Summary of Evidence Reviewed for the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infection Guidelines. Clin Infect Dis 2022; 74:S179-S192. [PMID: 35416975 DOI: 10.1093/cid/ciac044] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
In June 2019 the Centers for Disease Control and Prevention (CDC) convened an advisory group to assist in development of the 2021 CDC sexually transmitted infections (STI) guidelines. The advisory group on anal cancer screening and prevention met to formulate key questions in this field. The group examined published literature and abstracts to assess evidence and give recommendations for development of the CDC guidelines. This article summarizes key questions, evidence, recommendations, and areas for further research for the screening, diagnosis, and prevention of anal cancer.
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Affiliation(s)
- Luis F Barroso
- Internal Medicine/Infectious Diseases, Wake Forest University Health Sciences, Winston-Salem, North CarolinaUSA
| | - Elizabeth A Stier
- Obstetrics and Gynecology, Boston University School of Medicine, Boston Medical Center, Boston, MassachusettsUSA
| | - Richard Hillman
- Dysplasia and Anal Cancer Services, St Vincent's Hospital, Darlinghurst, Sydney, Australia
| | - Joel Palefsky
- Infectious Diseases, University of California, San Francisco, CaliforniaUSA
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Chaiwongkot A, Phanuphak N, Pankam T, Bhattarakosol P. Human papillomavirus 16 L1 gene methylation as a potential biomarker for predicting anal intraepithelial neoplasia in men who have sex with men (MSM). PLoS One 2021; 16:e0256852. [PMID: 34469465 PMCID: PMC8409669 DOI: 10.1371/journal.pone.0256852] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 08/17/2021] [Indexed: 12/18/2022] Open
Abstract
The human papillomavirus (HPV) 16 early promoter and L1 gene methylation were quantitatively measured using pyrosequencing assay in anal cells collected from men who have sex with men (MSM) to determine potential biomarkers for HPV-related anal cancer. The methylation patterns of HPV16 genes, including the early promoter (CpG 31, 37, 43, 52, and 58) and L1 genes (CpG 5600, 5606, 5609, 5615, 7136, and 7145), were analyzed in 178 anal samples. The samples were diagnosed as normal, anal intraepithelial neoplasia (AIN) 1, AIN2, and AIN3. Low methylation levels of the early promoter (< 10%) and L1 genes (< 20%) were found in all detected normal anal cells. In comparison, medium to high methylation (≥ 20–60%) in the early promoter was found in 1.5% (1/67) and 5% (2/40) of AIN1 and AIN2-3 samples, respectively. Interestingly, slightly increased L1 gene methylation levels (≥ 20–60%), especially at the HPV16 5’L1 regions CpGs 5600 and 5609, were demonstrated in AIN2-3 specimen. Moreover, a negative correlation between high HPV16 L1 gene methylation at CpGs 5600, 5609, 5615, and 7145 and a percentual CD4 count was found in AIN3 HIV positive cases. When comparing the methylation status of AIN2-3 to that of normal/AIN1 lesions, the results indicated the potential of using HPV16 L1 gene methylation as a biomarker for HPV-related cancer screening.
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Affiliation(s)
- Arkom Chaiwongkot
- Faculty of Medicine, Applied Medical Virology Research Unit, Chulalongkorn University, Bangkok, Thailand
- Faculty of Medicine, Department of Microbiology, Chulalongkorn University, Bangkok, Thailand
- * E-mail:
| | | | | | - Parvapan Bhattarakosol
- Faculty of Medicine, Applied Medical Virology Research Unit, Chulalongkorn University, Bangkok, Thailand
- Faculty of Medicine, Department of Microbiology, Chulalongkorn University, Bangkok, Thailand
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Hopp AM, Pant M, Sniedze S, Parsons LN, Hunt B, Giorgadze T. Correlation of anal cytology with follow-up histology and Human Papillomavirus genotyping: A 10-year experience from an academic medical center. Ann Diagn Pathol 2020; 50:151670. [PMID: 33310590 DOI: 10.1016/j.anndiagpath.2020.151670] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 11/16/2020] [Indexed: 11/29/2022]
Abstract
BACKGROUND Anal cytology (AC) is accepted as a practical screening modality for anal cancer. However, studies suggest that AC and anal biopsy dysplasia correlation is less robust than in cervicovaginal specimens. The current study goals were to look at our institutional experience in a subset of ACs and correlate with surgical pathology (SP), as well as evaluate their Human Papillomavirus (HPV) status. METHODS 377 ACs from 169 patients (151 males and 18 females) from 2008 to 2017 were included. HPV genotyping (n = 47) and SP within one year of AC (n = 58) were reviewed. RESULTS AC/SP was discrepant in 22 cases (37.9%), with a tendency towards AC underestimating the degree of dysplasia. Specifically, any abnormality on AC was 93.8% sensitive for detecting high-grade dysplasia (HGD). However, when requiring a high-grade AC diagnosis, the sensitivity decreases to 12.5%. "Other high-risk HPV" was the most common genotype (57.4%). When considered with all AC with a high-grade diagnosis, co-testing with HPV improved the sensitivity for HGD to 56.3%. Sensitivity improved further to 87.5% when only considering cases with both AC and HPV testing, and were high-risk HPV positive. Furthermore, following review and consensus diagnosis, 8 cases changed from "Discrepant" to "Agreed", reducing the discrepancy rate to 24.1%. Remaining discrepancies were explained by sampling error. CONCLUSION Given the enhanced sensitivity of AC and HPV testing together, and sampling error seen with AC leading to underestimating dysplasia, we recommend AC and HPV co-testing, as well as describing confounding factors in AC reports and obtaining consensus opinion in equivocal cases.
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Affiliation(s)
- Amanda M Hopp
- Medical College of Wisconsin, Department of Pathology, 9200 W Wisconsin Ave, Milwaukee, WI 53226, United States of America; Children's Wisconsin, Department of Pathology, 9200 W Wisconsin Ave, Milwaukee, WI 53226, United States of America.
| | - Mamta Pant
- Medical College of Wisconsin, Department of Pathology, 9200 W Wisconsin Ave, Milwaukee, WI 53226, United States of America
| | - Sally Sniedze
- Wisconsin Diagnostic Laboratories, 8777 W Connell Ave, Milwaukee, WI 53226, United States of America
| | - Lauren N Parsons
- Medical College of Wisconsin, Department of Pathology, 9200 W Wisconsin Ave, Milwaukee, WI 53226, United States of America; Children's Wisconsin, Department of Pathology, 9200 W Wisconsin Ave, Milwaukee, WI 53226, United States of America
| | - Bryan Hunt
- Medical College of Wisconsin, Department of Pathology, 9200 W Wisconsin Ave, Milwaukee, WI 53226, United States of America
| | - Tamara Giorgadze
- Medical College of Wisconsin, Department of Pathology, 9200 W Wisconsin Ave, Milwaukee, WI 53226, United States of America
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Patel AP, Schatz-Siemers NF, Dilcher TL, Goyal A. The interpretation of high-grade squamous intraepithelial lesion on anal cytology: a comparative analysis with the cervical Papanicolaou test. J Am Soc Cytopathol 2020; 9:540-549. [PMID: 32800528 DOI: 10.1016/j.jasc.2020.07.132] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 07/15/2020] [Accepted: 07/16/2020] [Indexed: 11/30/2022]
Abstract
INTRODUCTION Prior studies have shown that high-grade squamous intraepithelial lesion (HSIL) tends to be underdiagnosed on anal cytology. Our study aims to decipher the interpretative challenges of HSIL that are more specific to anal cytology specimens by comparing them to cervical Papanicolaou tests. MATERIALS AND METHODS One hundred cases each of anal and cervical cytology specimens with HSIL interpretation and concordant histologic follow-up were retrieved and diagnostically confirmed. Patient demographic data were obtained from the electronic medical record. The cytologic specimens were reviewed and statistically compared in terms of proportion of HSIL cells, HSIL patterns and types, and cytoplasmic area of HSIL cells (with digital image analysis). A P value of <0.05 was considered statistically significant. RESULTS Of the patients with anal HSIL, 97% were human immunodeficiency virus-positive and 60% were men who have sex with men. The anal cytology specimens significantly differed from the cervical ones in several respects: proportion of HSIL cells, cytoplasmic area of HSIL cells, cases with HSIL cells in syncytial groups (10 versus 57) and cases with keratinizing HSIL (45 versus 10). The P value was <0.0001 for all comparisons except for the proportion of HSIL cells (P = 0.001). CONCLUSIONS Anal cytologic HSIL, in contrast to its cervical counterpart, exhibits fewer abnormal cells and smaller size of the diagnostic cells with a higher percentage of keratinizing lesions. A careful scrutiny of the sample with an enhanced understanding of the morphology and better sampling may help improve the detection of anal HSIL on cytology.
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Affiliation(s)
- Ami P Patel
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York
| | - Nina F Schatz-Siemers
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York
| | - Thomas L Dilcher
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York
| | - Abha Goyal
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine-New York Presbyterian Hospital, New York, New York.
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Piyathilake CJ, Badiga S, Kumar R, Crowley MR, Burkholder GA, Raper JL. A rigorous exploration of anal HPV genotypes using a next-generation sequencing (NGS) approach in HIV-infected men who have sex with men at risk for developing anal cancer. Cancer Med 2020; 9:807-815. [PMID: 31769225 PMCID: PMC6970045 DOI: 10.1002/cam4.2720] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Revised: 11/05/2019] [Accepted: 11/06/2019] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND There are no HPV-based measures for managing anal cancer (AC) in HIV-infected (HIV+) men who have sex with men (MSM) because of the high positivity of high-risk (HR)-HPVs. As next-generation sequencing (NGS) is able to describe the composition of HPVs as percent (%) reads rather than positive vs negative results, we used NGS approach to detect HPVs in anal samples of HIV+ MSM to test its ability to differentiate those who are diagnosed with atypical squamous cells of unknown significance or greater (ASCUS+) from those who are free of such lesions and to understand the burden of HPV infections in relation to HPV vaccines. METHODS Study included 81 HIV+ MSM characterized for demographics, patient-reported outcome measures, HIV related laboratory measures and anal cytology. We summarized NGS HPV data using % read cut points (>0%->30%) and tested the relationship between % reads of HR-HPVs and risk of ASCUS+ using logistic regression. RESULTS Forty-six HPVs were detected at the >0% read cut point. The prevalence of any HR-HPVs varied from 100% to 40% with >0% to >30% reads while ≥99% were infected with HR-HPVs included or not included in the 9 valent HPV vaccine at the >0% read cut point. MSM with >30% HR-HPV reads were 4.5 times more likely to be diagnosed with ASCUS+ compared to ≤30% reads (P = .033). CONCLUSION NGS-based approach is more accurate than PCR-based HPV testing for identifying HIV+ MSM at risk for developing AC. We raise the concern regarding the efficacy of current HPV vaccines for preventing AC in this high-risk population.
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Affiliation(s)
| | - Suguna Badiga
- Department of Nutrition SciencesThe University of Alabama at Birmingham (UAB)BirminghamALUSA
| | - Ranjit Kumar
- UAB Center for Clinical & Translational ScienceThe University of Alabama at Birmingham (UAB)BirminghamALUSA
| | - Michael R. Crowley
- Department of GeneticsThe University of Alabama at Birmingham (UAB)BirminghamALUSA
| | - Greer A. Burkholder
- Division of Infectious DiseasesDepartment of MedicineThe University of Alabama at Birmingham (UAB)BirminghamALUSA
| | - James L. Raper
- Division of Infectious DiseasesDepartment of MedicineThe University of Alabama at Birmingham (UAB)BirminghamALUSA
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11
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Gonçalves JCN, Macedo ACL, Madeira K, Bavaresco DV, Dondossola ER, Grande AJ, da Rosa MI. Accuracy of Anal Cytology for Diagnostic of Precursor Lesions of Anal Cancer: Systematic Review and Meta-analysis. Dis Colon Rectum 2019; 62:112-120. [PMID: 30451747 DOI: 10.1097/dcr.0000000000001231] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Anal canal carcinoma is relevant because it commonly occurs in high-risk groups, and its incidence has been increasing. OBJECTIVE This study evaluated the accuracy of anal cytology in the screening of precursor lesions of anal cancer, compared with histopathologic examination as the reference, in all subjects and in men who have sex with men, HIV-infected men and women, and men who have sex with men and HIV-infected subgroups. DATA SOURCES The data included studies identified in the MEDLINE, Latin American and Caribbean Health Sciences, Cochrane Library, and Embase electronic databases, as well as in the grey literature. The search terms included anal cancer, anal dysplasia, anal intraepithelial neoplasia, screening, and anal cytology. STUDY SELECTION After excluding studies with no histopathological data and those with duplicate and missing data, 34 primary studies were included. INTERVENTION Cytology of anal smears was studied. MAIN OUTCOME MEASURES Sensitivity, specificity, diagnostic OR, and area under the curve were measured. RESULTS A total of 5093 patients were included. The pooled sensitivity of anal cytology was 85.0% (95% CI, 82.0%-87.0%) and pooled specificity was 43.2% (95% CI, 41.4%-45.1%) for the detection of anal intraepithelial neoplasia grade 2 or worse versus anal intraepithelial neoplasia grade 1 and normal when measuring all subjects. The accuracy of anal cytology was higher in the men who have sex with men and HIV-infected and men who have sex with men only subgroups. LIMITATIONS This study was limited by its specificity. CONCLUSIONS The study results support the hypothesis that cytology is a good test for the screening of anal cancer.
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Affiliation(s)
- João Carlos N Gonçalves
- Translational Biomedicine Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, Santa Catarina, Brazil
- Department of Medicine, Centro Universitário do Espírito Santo, University of Southern Santa Catarina, Colatina, Espírito Santo, Brazil
| | - Ana C L Macedo
- Translational Biomedicine Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, Santa Catarina, Brazil
- Department of Medicine, Centro Universitário do Espírito Santo, University of Southern Santa Catarina, Colatina, Espírito Santo, Brazil
| | - Kristian Madeira
- Translational Biomedicine Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, Santa Catarina, Brazil
| | - Daniela Vicente Bavaresco
- Translational Biomedicine Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, Santa Catarina, Brazil
| | - Eduardo Ronconi Dondossola
- Translational Biomedicine Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, Santa Catarina, Brazil
| | - Antônio José Grande
- Laboratory of Evidence in Health, Medicine and Health Sciences, University of State of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul, Brazil
| | - Maria Inês da Rosa
- Translational Biomedicine Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, Santa Catarina, Brazil
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12
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Silva M, Peixoto A, Sarmento JA, Coelho R, Macedo G. Anal cytology, histopathology and anoscopy in an anal dysplasia screening program: is anal cytology enough? REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2018; 110:109-114. [PMID: 29168646 DOI: 10.17235/reed.2017.4913/2017] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND AND AIM The human papilloma virus is the leading cause of anal squamous cell carcinoma. Cytological screening may reduce the associated morbidity and mortality. The aim of the study was to estimate the agreement between anal cytological examination, histopathology and anoscopic visual impression. METHODS A prospective study of patients who underwent anal dysplasia screening between 2011 and 2015, in a proctology clinic of a tertiary referral center. RESULTS During the study period, 141 patients (91% men, 87% with HIV infection) underwent 175 anal cytology tests. Of these, 33% were negative for intraepithelial lesions or malignancy (NILM), 22% were atypical squamous cells of uncertain significance (ASCUS), 33% were low-grade squamous intraepithelial lesion (LSIL) and 12% were high-grade squamous intraepithelial lesion (HSIL). With regard to anoscopic visual impression, 46% of patients had no lesions and excision/biopsy of the identified lesions was performed in the remaining patients. The weighted kappa-agreement between abnormal cytological results and anoscopic visual impression was moderate (k = 0.48). The weighted kappa-agreement between simultaneous anal cytological examinations and anal histopathologic findings was low (kappa = 0.20). With regard to the histological examination of cases with HSIL or superficially invasive squamous cell carcinoma, 64% of patients had dysplasia of a lower grade according to the cytological analysis (6 ASCUS, 18 LSIL and 4 NILM). CONCLUSION There was a poor correlation between anal cytology, histopathology and anoscopic visual impression and a high number of histological studies of HGD that were of a lower dysplastic degree according to the cytological examination. Therefore, anal cytology screening should not be used as the sole method of anal dysplasia screening.
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Affiliation(s)
- Marco Silva
- Gastroenterology, Centro Hospitalar São João, Portugal
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13
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Morency EG, Harbert T, Fatima N, Samolcyzk J, Maniar KP, Nayar R. Anal Cytology: Institutional Statistics, Correlation With Histology, and Development of Multidisciplinary Screening Program With Review of the Current Literature. Arch Pathol Lab Med 2018; 143:23-29. [DOI: 10.5858/arpa.2017-0242-ra] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Context.—
The incidence of anal cancer in the United States is on the rise in high-risk populations. The anal Papanicolaou test (APT) is advocated as a screening tool, in addition to digital rectal examination and high-resolution anoscopy.
Objective.—
To review our experience and the current literature to create, in cooperation with clinicians, a standardized screening and treatment algorithm given our large volume of APTs.
Data Sources.—
All APTs collected between January 2013 and June 2015 were reviewed and correlated with follow-up/concurrent biopsy diagnoses, and clinical and social history. In total, 1417 APTs were performed on 1185 patients and APT results were as follows: 17.4% (247 of 1417) unsatisfactory; 27.9% (395 of 1417) negative; 19.5% (276 of 1417) atypical squamous cells of undetermined significance (ASC-US); 24.1% (342 of 1417) low-grade squamous intraepithelial lesion (LSIL); 3.6% (51 of 1417) atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H); and 7.5% (106 of 1417) HSIL. In total 376 cases (26.5%) had concurrent/follow-up biopsy. Review of all unsatisfactory cases with squamous intraepithelial lesion (SIL) on biopsy showed LSIL in 19.2% (5 of 26). Anal Papanicolaou test with cytologic abnormality (ASC-US+) had an 83.8% (315 of 376) rate of biopsy-proven disease, and sensitivity was higher (92%) for high-grade anal intraepithelial neoplasia or worse (AIN2+). Overall detection of AIN2+ using ASC-US+ showed specificity of 26%, negative predictive value of 92%, and positive predictive value of 26%.
Conclusions.—
Anal cytology has a high abnormal rate (54.7%) and sensitivity but poor correlation with histologic grade. High unsatisfactory rate indicates need for improvement in sampling with 68.4% of cases having SIL on biopsy. Multidisciplinary effort led to improvements in sampling, cytologic interpretation, and development of a standardized management algorithm.
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Affiliation(s)
- Elizabeth G. Morency
- From the Department of Pathology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Tracey Harbert
- From the Department of Pathology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Nazneen Fatima
- From the Department of Pathology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Julia Samolcyzk
- From the Department of Pathology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Kruti P. Maniar
- From the Department of Pathology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Ritu Nayar
- From the Department of Pathology, Northwestern Memorial Hospital, Chicago, Illinois
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14
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Zaccarini DJ, Khurana KK. Histopathologic and Cytologic Follow-Up in High Risk Male Patients with Unsatisfactory Anal Cytology. PATHOLOGY RESEARCH INTERNATIONAL 2017; 2017:9780213. [PMID: 29075548 PMCID: PMC5624152 DOI: 10.1155/2017/9780213] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Accepted: 08/01/2017] [Indexed: 11/27/2022]
Abstract
OBJECTIVE Anal cytology is being increasingly used as part of anal cancer screening in patients at high risk for anal neoplasia. Most studies in anal cytology have focused on correlating the abnormal anal Pap smear with histopathologic outcomes. The aim of this study was to document histopathologic or repeat anal cytology outcomes in patients with unsatisfactory cytology. MATERIALS AND METHODS Unsatisfactory anal Pap tests in high risk male patients were correlated with follow-up histopathologic diagnoses or cytology. RESULTS 1205 anal tests were performed during the study period and 214 (17.8%) were unsatisfactory. Adequate follow-up cytology was available in 75 cases and revealed epithelial cell abnormality (ECA) in 40% [30/75] (atypical squamous cells of undetermined significance (ASCUS) [20%] and low-grade squamous intraepithelial lesions (LGSIL) [20%]) and was negative for intraepithelial lesion or malignancy (NILM) in 60% [45/75] of cases. 28.7% of unsatisfactory Pap smears had unsatisfactory repeat cytology. Histopathological follow-up on these unsatisfactory Pap smears revealed anal intraepithelial neoplasia (AIN) 1 and AIN 2/3 or 2/3+ in 39% and 18% of the total number of biopsy cases, respectively. CONCLUSIONS High risk male patients with unsatisfactory Pap smears are at significant risk of epithelial cell abnormality and histopathologically verifiable anal intraepithelial lesions.
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Affiliation(s)
| | - Kamal K. Khurana
- Department of Pathology, SUNY Upstate Medical University, Syracuse, NY, USA
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15
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Krishnamurti U, Unger ER. Pathobiology of human papillomaviruses in human immunodeficiency virus - Infected persons. Semin Diagn Pathol 2017; 34:364-370. [PMID: 28549522 DOI: 10.1053/j.semdp.2017.04.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
There is a complex interrelationship between human papillomaviruses (HPV) and human immunodeficiency viruses (HIV) that has been recognized from the start of the HIV epidemic. Cervical cancer was used as a surveillance indicator for acquired immunodeficiency syndrome (AIDS) before definitive identification of the viral etiology of either condition were known. Careful epidemiologic studies combined with clinical and laboratory measures of HPV, HPV-associated disease, and HIV have helped us understand many aspects of the relationship between these two virus groups; however, questions remain. The histopathology associated with HPV is identical in HIV-positive and negative patients though the lesions are more frequent, with higher frequency of multiple HPV types, and persistent in HIV infected individuals. In this review we will briefly explain the pathobiology of HPV in HIV-infected persons and the potential impact of secondary (screening) and primary (vaccination) prevention to reduce HPV-associated disease in those infected with HIV.
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Affiliation(s)
- Uma Krishnamurti
- Department of Pathology, Emory University School of Medicine, United States
| | - Elizabeth R Unger
- Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Road, MS G41, Atlanta, GA 30329, United States.
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16
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Benevolo M, Donà MG, Ravenda PS, Chiocca S. Anal human papillomavirus infection: prevalence, diagnosis and treatment of related lesions. Expert Rev Anti Infect Ther 2016; 14:465-77. [PMID: 27050294 DOI: 10.1586/14787210.2016.1174065] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Human papillomavirus (HPV) infection is mostly asymptomatic, but may also have many diverse clinical signs encompassing benign ano-genital lesions, and carcinomas. Recently, interest has also particularly focused on anal cancer since, over the last decades, its incidence has been greatly increasing in developed countries, both in women and men and is drastically higher in specific risk groups, such as men who have sex with men (MSM) and HIV-1 infected individuals. Approximately 88% of anal cancer cases worldwide are associated with HPV infection. This review summarizes our current understanding of anal HPV infection, discussing its epidemiology and risk factors in various populations, and the state of the art in the detection of anal HPV infection and its related lesions through both cytology and histology. Finally, we discuss the clinical management and therapy for these lesions.
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Affiliation(s)
- Maria Benevolo
- a Pathology Department , Regina Elena National Cancer Institute, IRCCS , Rome , Italy
| | - Maria Gabriella Donà
- b Sexually Transmitted Infection (STI) Unit , San Gallicano Dermatologic Institute, IRCCS , Rome , Italy
| | - Paola Simona Ravenda
- c Unit of Gastrointestinal and Neuroendocrine Tumours , European Institute of Oncology , Milan , Italy
| | - Susanna Chiocca
- d Department of Experimental Oncology , European Institute of Oncology (IEO) , Milan , Italy
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17
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Padilla-España L, Repiso-Jiménez JB, Fernández-Sánchez F, Pereda T, Rivas-Ruiz F, Fernández-Morano T, de la Torre-Lima J, Palma F, Redondo M, de Troya-Martín M. [Effectiveness of human papillomavirus genotyping for detection of high-grade anal intraepithelial neoplasia compared to anal cytology]. Enferm Infecc Microbiol Clin 2016; 34:400-5. [PMID: 26976378 DOI: 10.1016/j.eimc.2016.02.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2015] [Revised: 02/01/2016] [Accepted: 02/03/2016] [Indexed: 12/17/2022]
Abstract
INTRODUCTION The incidence of high-grade anal intraepithelial neoplasia (HGAIN) -with an aetiological based on high-risk types of human papillomavirus- is increasing in some high-risk groups. Screening for HGAIN includes routine anal cytology and, more recently, HPV genotyping. The main objective of this study was to determine the sensitivity and specificity of anal cytology and HPV genotyping for the detection of HGAIN. MATERIALS AND METHODS This is a study to determine the correlation of cytological and microbiological findings with anal biopsy findings in a cohort of patients at high risk of developing AIN referred to the department of sexually transmitted infections of the Hospital Costa del Sol, Spain, between January 2008 and December 2014. RESULTS Of the 151 patients subjected to screening, a total of 92 patients, all of them with the result of three screening test (anal cytology, genotyping and biopsy) were included in the study. Just under two-thirds (62%) of them were HIV-positive. The sensitivity and specificity of anal cytology to detect HGAIN were 52.8 and 85.7%, respectively (k: 0.328), and 78 and 62.8% to detect two or more HPV oncogenic genotypes (k: 0.417). The detection of oncogenic HPV genotypes allowed the identification of 23 new cases of HGAIN that had been underdiagnosed with anal cytology, with 14 cases containing at least three high-risk genotypes. CONCLUSION Anal cytology did not show enough sensitivity in HGAIN screening. HPV genotyping has shown to be a useful tool to detect HGAIN cases, although it could lead to an over-diagnosis as a solitary screening procedure.
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Affiliation(s)
| | | | | | - Teresa Pereda
- Anatomía Patológica, Hospital Costa del Sol , Marbella, España
| | | | | | | | - Fermín Palma
- Cirugía General, Hospital Costa del Sol, Marbella, España
| | - Maximino Redondo
- Universidad de Málaga, Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Málaga, España
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18
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Long KC, Menon R, Bastawrous A, Billingham R. Screening, Surveillance, and Treatment of Anal Intraepithelial Neoplasia. Clin Colon Rectal Surg 2016; 29:57-64. [PMID: 26929753 DOI: 10.1055/s-0035-1570394] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The prevalence of anal intraepithelial neoplasia has been increasing, especially in high-risk patients, including men who have sex with men, human immunodeficiency virus positive patients, and those who are immunosuppressed. Several studies with long-term follow-up have suggested that rate of progression from high-grade squamous intraepithelial lesions to invasive anal cancer is ∼ 5%. This number is considerably higher for those at high risk. Anal cytology has been used to attempt to screen high-risk patients for disease; however, it has been shown to have very little correlation to actual histology. Patients with lesions should undergo history and physical exam including digital rectal exam and standard anoscopy. High-resolution anoscopy can be considered as well, although it is of questionable time and cost-effectiveness. Nonoperative treatments include expectant surveillance and topical imiquimod or 5-fluorouracil. Operative therapies include wide local excision and targeted ablation with electrocautery, infrared coagulation, or cryotherapy. Recurrence rates remain high regardless of treatment delivered and surveillance is paramount, although optimal surveillance regimens have yet to be established.
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Affiliation(s)
- Kevin C Long
- Swedish Colon and Rectal Clinic, Swedish Medical Center Department of Surgery, Seattle, Washington
| | - Raman Menon
- Swedish Colon and Rectal Clinic, Swedish Medical Center Department of Surgery, Seattle, Washington
| | - Amir Bastawrous
- Swedish Colon and Rectal Clinic, Swedish Medical Center Department of Surgery, Seattle, Washington
| | - Richard Billingham
- Swedish Colon and Rectal Clinic, Swedish Medical Center Department of Surgery, Seattle, Washington
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19
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Leeds IL, Fang SH. Anal cancer and intraepithelial neoplasia screening: A review. World J Gastrointest Surg 2016; 8:41-51. [PMID: 26843912 PMCID: PMC4724586 DOI: 10.4240/wjgs.v8.i1.41] [Citation(s) in RCA: 114] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2015] [Revised: 10/02/2015] [Accepted: 11/11/2015] [Indexed: 02/06/2023] Open
Abstract
This review focuses on the early diagnosis of anal cancer and its precursor lesions through routine screening. A number of risk-stratification strategies as well as screening techniques have been suggested, and currently little consensus exists among national societies. Much of the current clinical rationale for the prevention of anal cancer derives from the similar tumor biology of cervical cancer and the successful use of routine screening to identify cervical cancer and its precursors early in the disease process. It is thought that such a strategy of identifying early anal intraepithelial neoplasia will reduce the incidence of invasive anal cancer. The low prevalence of anal cancer in the general population prevents the use of routine screening. However, routine screening of selected populations has been shown to be a more promising strategy. Potential screening modalities include digital anorectal exam, anal Papanicolaou testing, human papilloma virus co-testing, and high-resolution anoscopy. Additional research associating high-grade dysplasia treatment with anal cancer prevention as well as direct comparisons of screening regimens is necessary to develop further anal cancer screening recommendations.
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20
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Johnson GE, Nguyen ML, Krishnamurti U, Seydafkan S, Flowers L, Ehdaivand S, Mosunjac M. Cytology as a screening tool for anal squamous intraepithelial lesion for HIV positive men: 10-year experience in an inner city hospital. J Am Soc Cytopathol 2015; 5:145-153. [PMID: 31042517 DOI: 10.1016/j.jasc.2015.08.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Revised: 08/26/2015] [Accepted: 08/26/2015] [Indexed: 01/26/2023]
Abstract
INTRODUCTION Human papillomavirus (HPV) and anal carcinoma are prevalent in high-risk patients including human immunodeficiency virus (HIV)-positive patients. There are currently no clear guidelines for screening, however. We assessed anal cytology specimens and HPV testing at an inner-city hospital by correlating anal cytology with anal biopsy (bx), and evaluated if results differed with traditional proctoscopy (TP) or high-resolution anoscopy (HRA). MATERIALS AND METHODS 209 anal cytology and subsequent biopsies taken during the period 2003-2014 from 152 male patients were reviewed. Demographic data for age, sex, HIV, HPV, cytology, histology, and the method of biopsy were analyzed. RESULTS All specimens were followed by a biopsy within a period of 6 months. Ninety-seven percent of patients were HIV-positive and 43% had AIDS. Lesions most diagnosed on cytology were low-grade squamous intraepithelial lesion (LSIL) (52%) and atypical squamous cells of undetermined significance (ASC-US) (21.5%). Lesions most diagnosed on bx were anal intraepithelial neoplasia (AIN) grade 2-3 (52%) and AIN grade 1 (37%). Almost all ASC-US cases tested for HPV were positive (97%). There was cytology histology correlation in 48% of LSIL and 83% of high-grade squamous intraepithelial lesions. Anal cytology had 97% sensitivity in detecting AIN and carcinoma and a positive predictive value of 96%. There was no difference in rate of detection of AIN 1and AIN 2-3 on bx using TP versus HRA. CONCLUSION Screening in high-risk patients detected almost all high- and low-grade squamous intraepithelial lesions, however, anal cytology alone could not predict the degree of dysplasia. It may be prudent to perform anal bx in all atypical anal cytology. Clear guidelines are needed for screening of a high risk population.
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Affiliation(s)
- Gina E Johnson
- Department of Pathology and Laboratory Medicine, Emory University, 1364 Clifton Rd. NE, Atlanta, Georgia.
| | - Minh Ly Nguyen
- Department of Obstetrics and Gynecology, Emory University, Atlanta, Georgia
| | - Uma Krishnamurti
- Department of Pathology and Laboratory Medicine, Emory University, 1364 Clifton Rd. NE, Atlanta, Georgia
| | | | - Lisa Flowers
- Division of Infectious Disease, Department of Internal Medicine, Emory University, Atlanta, Georgia
| | - Shahrzad Ehdaivand
- Department of Pathology and Laboratory Medicine, Emory University, 1364 Clifton Rd. NE, Atlanta, Georgia
| | - Marina Mosunjac
- Department of Pathology and Laboratory Medicine, Emory University, 1364 Clifton Rd. NE, Atlanta, Georgia
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21
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Moscicki AB, Darragh TM, Berry-Lawhorn JM, Roberts JM, Khan MJ, Boardman LA, Chiao E, Einstein MH, Goldstone SE, Jay N, Likes WM, Stier EA, Welton ML, Wiley DJ, Palefsky JM. Screening for Anal Cancer in Women. J Low Genit Tract Dis 2015; 19:S27-42. [PMID: 26103446 PMCID: PMC4479419 DOI: 10.1097/lgt.0000000000000117] [Citation(s) in RCA: 100] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE The incidence of anal cancer is higher in women than men in the general population and has been increasing for several decades. Similar to cervical cancer, most anal cancers are associated with human papillomavirus (HPV), and it is believed that anal cancers are preceded by anal high-grade squamous intraepithelial lesions (HSIL). Our goals were to summarize the literature on anal cancer, HSIL, and HPV infection in women and to provide screening recommendations in women. METHODS A group of experts convened by the American Society for Colposcopy and Cervical Pathology and the International Anal Neoplasia Society reviewed the literature on anal HPV infection, anal SIL, and anal cancer in women. RESULTS Anal HPV infection is common in women but is relatively transient in most. The risk of anal HSIL and cancer varies considerably by risk group, with human immunodeficiency virus-infected women and those with a history of lower genital tract neoplasia at highest risk compared with the general population. CONCLUSIONS While there are no data yet to demonstrate that identification and treatment of anal HSIL leads to reduced risk of anal cancer, women in groups at the highest risk should be queried for anal cancer symptoms and required to have digital anorectal examinations to detect anal cancers. Human immunodeficiency virus-infected women and women with lower genital tract neoplasia may be considered for screening with anal cytology with triage to treatment if HSIL is diagnosed. Healthy women with no known risk factors or anal cancer symptoms do not need to be routinely screened for anal cancer or anal HSIL.
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Affiliation(s)
- Anna-Barbara Moscicki
- Division of Adolescent and Young Adult Medicine, Department of Pediatrics, University of California, San Francisco, CA, USA
| | - Teresa M. Darragh
- Department of Clinical Pathology, University of California, San Francisco, CA, USA
| | | | | | - Michelle J. Khan
- Division of Women's Reproductive Healthcare Department of OB/GYN, School of Medicine, University of Alabama at Birmingham, AL, USA
| | - Lori A. Boardman
- Florida Hospital for Women, Florida Hospital System, University of Central Florida College of Medicine, FL, USA
| | - Elizabeth Chiao
- Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey VA Medical Center, Houston, TX, USA
| | - Mark H. Einstein
- Department of Obstetrics and Gynecology & Women's Health, Albert Einstein College of Medicine, Montefiore Medical Center, New York, NY
| | | | - Naomi Jay
- Anal Neoplasia Clinic, Research and Education (ANCRE) Center, University of California, San Francisco, CA, USA
| | - Wendy M. Likes
- College of Medicine, Department of Obstetrics and Gynecology, University of Tennessee Health Science Center, Memphis, TN, USA
| | | | - Mark Lane Welton
- Colon & Rectal Surgery, Stanford University School of Medicine Stanford Hospital and Clinics, Stanford, CA, USA
| | - Dorothy J. Wiley
- School of Nursing, University of California, Los Angeles, CA, USA
| | - Joel M. Palefsky
- Department of Infectious Diseases, University of California, San Francisco, CA, USA
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22
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Cheng SH, Wang CC, Chang SL, Chu FY, Hsueh YM. Oncogenic human papillomavirus is not helpful for cytology screening of the precursor lesions of anal cancers in Taiwanese men who are infected with human immunodeficiency virus. Int J Clin Oncol 2015; 20:943-51. [PMID: 25712159 DOI: 10.1007/s10147-015-0804-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2014] [Accepted: 02/10/2015] [Indexed: 01/03/2023]
Abstract
BACKGROUND Homosexual men infected with human immunodeficiency virus (HIV) are at increased risk of developing anal cancer. The aim of this study was to assess the clinical sensitivity of anal cytology analysis and oncogenic human papillomavirus (HPV) detection for predicting histological anal intraepithelial neoplasia. METHODS Between March 2011 and December 2013, we enrolled 196 HIV-positive men in Taoyuan General Hospital, Taiwan. We analyzed the results of thin-preparation anal Pap smears, HPV genotyping, and histology of anoscopic biopsy samples. RESULTS The mean age (±standard deviation) was 31.43 (±8.74) years. The proportion (95 % confidence interval) with abnormal thin-preparation anal cytology was 36.2 % (29.8-43.2 %): 16.8 % (12.2-22.7 %) atypical squamous cells of undetermined significance, 14.8 % (10.5-20.4 %) low-grade squamous intraepithelial lesions, and 4.6 % (2.4-8.5 %) high-grade squamous intraepithelial lesions. At least one HPV genotype was detected in 90.8 % of subjects, and the mean number of HPV infection types was 4.41 (±3.24).The frequency of histological high-grade anal intraepithelial lesions was 7.14 % (95 % confidence interval 4.3-11.6 %). Anal cytology yielding atypical squamous cells of undetermined significance or higher grades resulted in a sensitivity of 64.3 %, specificity of 65.9 %, positive predictive value of 12.7 %, and negative predictive value of 96 %. Using both oncogenic HPV and cytology did not provide better performance. CONCLUSIONS Anal cytology yielding atypical squamous cells of undetermined significance or higher grades could detect two-thirds of high-grade anal intraepithelial neoplasias in HIV-infected men and should be promoted for anal cancer prevention.
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Affiliation(s)
- Shu-Hsing Cheng
- School of Public Health, College of Public Health and Nutrition, Taipei Medical University, No. 250 Wu-Hsing St, Taipei, Taiwan.,Department of Infectious Diseases, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan
| | - Chi-Chao Wang
- Department of Surgery, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan
| | - Shih-Lung Chang
- Department of Pathology, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan
| | - Fang-Yeh Chu
- School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei, Taiwan.,Department of Clinical Pathology, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Yu-Mei Hsueh
- School of Public Health, College of Public Health and Nutrition, Taipei Medical University, No. 250 Wu-Hsing St, Taipei, Taiwan. .,Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
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Padilla-España L, Repiso-Jiménez B, Fernández-Sánchez F, Frieyro-Elicegui M, Fernández-Morano T, Pereda T, Rivas-Ruiz F, Redondo M, de-Troya Martín M. Utilidad de la detección del virus del papiloma humano en el cribado de neoplasia intraepitelial anal en pacientes con conductas de riesgo. Enferm Infecc Microbiol Clin 2014; 32:560-4. [DOI: 10.1016/j.eimc.2014.03.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2013] [Revised: 03/23/2014] [Accepted: 03/28/2014] [Indexed: 01/16/2023]
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Selvaggi SM. Anal-rectal cytology as a screening tool for the detection of anal intraepithelial neoplasia in HIV-positive men. J Am Soc Cytopathol 2014; 3:151-155. [PMID: 31051739 DOI: 10.1016/j.jasc.2014.01.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2013] [Accepted: 01/10/2014] [Indexed: 06/09/2023]
Abstract
INTRODUCTION Use of anal-rectal cytology is on the rise as a screening tool for the detection of anal squamous lesions in human immunodeficiency virus (HIV)-positive individuals. The purpose of this 5-year retrospective study was to determine the utility of routine anal-rectal screening for the detection of squamous lesions in HIV-positive patients with histology correlation. MATERIALS AND METHODS From January 1, 2008 through December 31, 2012, 448 anal-rectal Papanicolaou tests were performed on HIV-positive men, of which 133 were referred for high-resolution anoscopy. RESULTS Of the 448 cases, 184 (41%) were classified as atypical squamous cells of undetermined significance or above, of which 133 (72%) had histologic correlation. Nine (7%) were negative, 64 (48%) were anal intraepithelial neoplasia (AIN) 1, 36 (27%) were AIN 2, 21 (16%) were AIN 3, and 3 (2%) were squamous cell carcinoma. CONCLUSIONS The results of this study support the use of anal-rectal cytology as a screening tool in the detection of anal intraepithelial neoplasia, particularly in high-risk populations.
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Affiliation(s)
- Suzanne M Selvaggi
- Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, Wisconsin.
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Abstract
Diagnosis, follow up, and treatment of anal intraepithelial neoplasia are complex and not standardized. This may be partly caused by poor communication of biopsy and cytology findings between pathologists and clinicians as a result of a disparate and confusing terminology used to classify these lesions. This article focuses on general aspects of epidemiology and on clarifying the current terminology of intraepithelial squamous neoplasia, its relationship with human papilloma virus infection, and the current methods that exist to diagnose and treat this condition.
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Abstract
PURPOSE OF REVIEW The growing burden of non-AIDS defining malignancies (non-ADMs) among people living with HIV/AIDS (PLWHA) highlights the need for cancer prevention and early detection. In this article, we propose screening guidelines for non-ADMs in PLWHA. RECENT FINDINGS A number of recent findings may help direct cancer screening guidelines in PLWHA. Screening for lung cancer with low-dose helical chest computerized tomography (LDCT) in the National Lung Screening Trial data demonstrated a decrease in lung cancer and all-cause mortality. Recent studies have demonstrated a favorable experience among PLWHA with liver transplantation. Overdiagnosis is common with breast and prostate cancer screening. Anal cancer rates were substantially higher for HIV-infected MSM, other men and women than for HIV-uninfected individuals. SUMMARY Screening recommendations for the general population can be applied to PLWHA patients for breast, colon and prostate cancer. Screening for lung cancer with LDCT could be considered in PLWHA at risk. American Association for the Study of Liver Diseases screening recommendations with biennial ultrasonography may be applied to at-risk PLWHA for hepatocellular carcinoma. All HIV-infected adults should be offered anal cancer screening as part of clinical care at specialized centres.
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Affiliation(s)
- Deepthi Mani
- Division of Internal Medicine, Multicare Good Samaritan Hospital, Puyallup, WA, USA
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