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Meta-Analysis
. 2022 Dec 1;151(11):1889-1901.
doi: 10.1002/ijc.34199. Epub 2022 Aug 6.

A systematic review and meta-analysis of cytology and HPV-related biomarkers for anal cancer screening among different risk groups

Megan A Clarke  1 , Ashish A Deshmukh  2 , Ryan Suk  2 , Jennifer Roberts  3 , Richard Gilson  4 , Naomi Jay  5 , Elizabeth A Stier  6 , Nicolas Wentzensen  1
Affiliations
Meta-Analysis

A systematic review and meta-analysis of cytology and HPV-related biomarkers for anal cancer screening among different risk groups

Megan A Clarke et al. Int J Cancer. .

Erratum in

Abstract

To inform optimal approaches for detecting anal precancers, we performed a systematic review and meta-analysis of the diagnostic accuracy of anal cancer screening tests in different populations with elevated risk for anal cancer. We conducted a literature search of studies evaluating tests for anal precancer and cancer (anal intraepithelial neoplasia grade 2 or worse, AIN2+) published between January 1, 1997 to September 30, 2021 in PubMed and Embase. Titles and abstracts were screened for inclusion and included articles underwent full-text review, data abstraction and quality assessment. We estimated the prevalence of AIN2+ and calculated summary estimates and 95% confidence intervals (CI) of test positivity, sensitivity and specificity and predictive values of various testing strategies, overall and among population subgroups. A total of 39 articles were included. The prevalence of AIN2+ was 20% (95% CI, 17-29%), and ranged from 22% in men who have sex with men (MSM) living with HIV to 13% in women and 12% in MSM without HIV. The sensitivity and specificity of cytology and HPV testing were 81% and 62% and 92% and 42%, respectively, and 93% and 33%, respectively for cytology and HPV co-testing. AIN2+ risks were similar among those testing positive for cytology, HPV, or co-testing. Limited data on other biomarkers (HPV E6/E7 mRNA and p16/Ki-67 dual stain), suggested higher specificity, but lower sensitivity compared with anal cytology and HPV. Our findings provide important evidence for the development of clinical guidelines using anal cytology and HPV testing for anal cancer screening.

Keywords: HPV testing; anal cancer; anal precancer; cytology; screening.

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Conflict of interest statement

Conflict of Interest:

Drs. Clarke, Deshmukh, Gilson, Suk and Wentzensen: No conflicts

Dr. Naomi Jay has received consulting fees from Merck Pharmaceuticals, and has received support for conference travel and attendance from ASCCP. Dr. Jay served in an unpaid role as the past president and is a current unpaid Board Member and Anal Cancer Screening Guidelines’ Task Force Leader of the International Anal Neoplasia Society.

Dr. Elizabeth Stier has received honorariums from the Physicians’ Research Network and the British Association for Sexual Health and HIV. Dr. Steir has received reimbursement for travel from the British Association for Sexual Health and HIV, Eurogin Congress, and ASCCP. Dr. Steir serves as an unpaid leader of the International Anal Neoplasia Society’s Anal Cancer Screening Guidelines’ Task Force, and has received in-kind support for HPV testing from Hologic, LLC and Qiagen.

Dr. Jennifer Roberts has received payment from Sonic Healthcare, and consumables and antibodies donated from Hologic Australia and Roche Australia, respectively.

Figures

Figure 1.
Figure 1.. Summary ROC curves for the Performance of Anal Cytology at an ASC-US+ Threshold for AIN2+ Detection.
Summary ROC curves are plotted for all studies (A), for studies of MSM living with HIV (B), and for studies of women (C). Individual estimates for the sensitivity and specificity of cytology at an ASC-US+ threshold for AIN2+ are shown as hollow circles, with their size determined by the total number of study participants, and the summary estimate is indicated by a solid red square with a 95% confidence region (orange dashed line). The summary ROC curve is plotted (solid green line) and the 95% prediction region (green dashed line) represents potential values of sensitivity and specificity that might be observed in a future study by describing the full extent of uncertainty of the summary points. Abbreviations: ROC, receiver operating characteristic curve; ASC-US+, atypical squamous cells of undetermined significance or worse; AIN2+, anal intraepithelial neoplasia grade 2 or worse; HSROC, hierarchical summary ROC curve
Figure 2.
Figure 2.. Summary ROC curves for the Performance of High-Risk HPV Testing for AIN2+ Detection.
Summary ROC curves are plotted for all studies (A), for studies of MSM living with HIV (B), and for studies of women (C). Individual estimates for the sensitivity and specificity of high-risk HPV testing for AIN2+ are shown as hollow circles, with their size determined by the total number of study participants, and the summary estimate is indicated by a solid red square with a 95% confidence region (orange dashed line). The summary ROC curve is plotted (solid green line) and the 95% prediction region (green dashed line) represents potential values of sensitivity and specificity that might be observed in a future study by describing the full extent of uncertainty of the summary points. Abbreviations: ROC, receiver operating characteristic curve; HPV, human papillomavirus; AIN2+, anal intraepithelial neoplasia grade 2 or worse; HSROC, hierarchical summary ROC curve
Figure 3.
Figure 3.. The Absolute Risk of AIN2+ for Cytology, High-Risk HPV, and Co-testing.
The pre-and post-test risks of AIN2+ with 95% confidence intervals are plotted for anal cytology (ASC-US threshold), high-risk HPV testing, and HPV and cytology co-testing using data from 11 studies that evaluated all three strategies in the same study. The percentage with a given test result are shown in parentheses next to each result. Baseline risk corresponds to the prevalence of AIN2+ (i.e., pre-test risk). Abbreviations: AIN2+, anal intraepithelial neoplasia grade 2 or worse; HPV, human papillomavirus; ASC-US+, atypical squamous cells of undetermined significance or worse; NILM, negative for intraepithelial neoplasia or malignancy; AIN2+, anal intraepithelial neoplasia grade 2 or worse
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Comment in

References

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