The accuracy of anal swab–based tests to detect high-grade anal intraepithelial neoplasia in HIV-infected patients: A systematic review and meta-analysis

Fernando Dias Gonçalves Lima, Janine D. Viset, Mariska M. G. Leeflang, Jacqueline Limpens, Jan M. Prins, Henry J. C. de Vries

Research output: Contribution to journalReview articleAcademicpeer-review

Abstract

Background. The incidence of high-risk human papillomavirus (HR-HPV)–induced anal cancer is increasingly problematic among HIV-positive patients. Anal cancer is preceded by precursor lesions, anal intraepithelial neoplasia (AIN). AIN detection requires high-resolution anoscopy, a cumbersome and time-consuming procedure. We aggregated evidence on anal swab–based tests to detect AIN in HIV-positive patients. Methods. We searched MEDLINE and EMBASE for cross-sectional studies on AIN detection with anal cytology, HR-HPV DNA detection, HPV E6/E7 mRNA analysis, and P16INK4a and Ki-67 immunostaining. Summary estimates of sensitivity and specificity were calculated using bivariate logistic regression. Cytology was reported using the terms squamous intra-epithelial lesion (SIL) for AIN and high-grade SIL (HSIL) for high-grade AIN (HGAIN). Results. We included 22 studies. Using cytology with a cutoff of any SIL to detect HGAIN, we detected a sensitivity of 82% (95% CI, 74%–87%) and specificity of 45% (95% CI, 44%–66%); with the cutoff of HSIL, the sensitivity was 44% (95% CI, 45%–67%) and the specificity was 79% (95% CI, 69%-87%). The sensitivity of HPV DNA to detect HGAIN was 91% (95% CI, 82%–95%) and the specificity was 27% (95% CI, 21%–33%). For MSM, the positive predictive value (PPV) of cytology with a cutoff of any SIL was 36% (95% CI, 23%–50%) and the negative predictive value (NPV) was 87% (95% CI, 78%–93%), whereas cytology with a cutoff of HSIL had a PPV of 62% (95% CI, 50%–73%) and an NPV of 78% (95% CI, 65%–87%). The PPV of HR-HPV DNA detection was 37% (95% CI, 20%–57%) and the NPV was 87% (95% CI, 79%–93%). Conclusions. Given its sensitivity, cytology with a cutoff of any SIL could be considered as a triaging method, whereas cytology with a cutoff of HSIL had better specificity and could be used for quality assurance. HR-HPV DNA detection had poor specificity and PPV, making it unsuitable for triage.
Original languageEnglish
JournalOpen Forum Infectious Diseases
Volume6
Issue number5
DOIs
Publication statusPublished - 1 Jan 2019
Externally publishedYes

Cite this

@article{051f3f3c20a6452c9402e9434a402a45,
title = "The accuracy of anal swab–based tests to detect high-grade anal intraepithelial neoplasia in HIV-infected patients: A systematic review and meta-analysis",
abstract = "Background. The incidence of high-risk human papillomavirus (HR-HPV)–induced anal cancer is increasingly problematic among HIV-positive patients. Anal cancer is preceded by precursor lesions, anal intraepithelial neoplasia (AIN). AIN detection requires high-resolution anoscopy, a cumbersome and time-consuming procedure. We aggregated evidence on anal swab–based tests to detect AIN in HIV-positive patients. Methods. We searched MEDLINE and EMBASE for cross-sectional studies on AIN detection with anal cytology, HR-HPV DNA detection, HPV E6/E7 mRNA analysis, and P16INK4a and Ki-67 immunostaining. Summary estimates of sensitivity and specificity were calculated using bivariate logistic regression. Cytology was reported using the terms squamous intra-epithelial lesion (SIL) for AIN and high-grade SIL (HSIL) for high-grade AIN (HGAIN). Results. We included 22 studies. Using cytology with a cutoff of any SIL to detect HGAIN, we detected a sensitivity of 82{\%} (95{\%} CI, 74{\%}–87{\%}) and specificity of 45{\%} (95{\%} CI, 44{\%}–66{\%}); with the cutoff of HSIL, the sensitivity was 44{\%} (95{\%} CI, 45{\%}–67{\%}) and the specificity was 79{\%} (95{\%} CI, 69{\%}-87{\%}). The sensitivity of HPV DNA to detect HGAIN was 91{\%} (95{\%} CI, 82{\%}–95{\%}) and the specificity was 27{\%} (95{\%} CI, 21{\%}–33{\%}). For MSM, the positive predictive value (PPV) of cytology with a cutoff of any SIL was 36{\%} (95{\%} CI, 23{\%}–50{\%}) and the negative predictive value (NPV) was 87{\%} (95{\%} CI, 78{\%}–93{\%}), whereas cytology with a cutoff of HSIL had a PPV of 62{\%} (95{\%} CI, 50{\%}–73{\%}) and an NPV of 78{\%} (95{\%} CI, 65{\%}–87{\%}). The PPV of HR-HPV DNA detection was 37{\%} (95{\%} CI, 20{\%}–57{\%}) and the NPV was 87{\%} (95{\%} CI, 79{\%}–93{\%}). Conclusions. Given its sensitivity, cytology with a cutoff of any SIL could be considered as a triaging method, whereas cytology with a cutoff of HSIL had better specificity and could be used for quality assurance. HR-HPV DNA detection had poor specificity and PPV, making it unsuitable for triage.",
author = "{Gon{\cc}alves Lima}, {Fernando Dias} and Viset, {Janine D.} and Leeflang, {Mariska M. G.} and Jacqueline Limpens and Prins, {Jan M.} and {de Vries}, {Henry J. C.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1093/ofid/ofz191",
language = "English",
volume = "6",
journal = "Open Forum Infectious Diseases",
issn = "2328-8957",
number = "5",

}

The accuracy of anal swab–based tests to detect high-grade anal intraepithelial neoplasia in HIV-infected patients: A systematic review and meta-analysis. / Gonçalves Lima, Fernando Dias; Viset, Janine D.; Leeflang, Mariska M. G.; Limpens, Jacqueline; Prins, Jan M.; de Vries, Henry J. C.

In: Open Forum Infectious Diseases, Vol. 6, No. 5, 01.01.2019.

Research output: Contribution to journalReview articleAcademicpeer-review

TY - JOUR

T1 - The accuracy of anal swab–based tests to detect high-grade anal intraepithelial neoplasia in HIV-infected patients: A systematic review and meta-analysis

AU - Gonçalves Lima, Fernando Dias

AU - Viset, Janine D.

AU - Leeflang, Mariska M. G.

AU - Limpens, Jacqueline

AU - Prins, Jan M.

AU - de Vries, Henry J. C.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background. The incidence of high-risk human papillomavirus (HR-HPV)–induced anal cancer is increasingly problematic among HIV-positive patients. Anal cancer is preceded by precursor lesions, anal intraepithelial neoplasia (AIN). AIN detection requires high-resolution anoscopy, a cumbersome and time-consuming procedure. We aggregated evidence on anal swab–based tests to detect AIN in HIV-positive patients. Methods. We searched MEDLINE and EMBASE for cross-sectional studies on AIN detection with anal cytology, HR-HPV DNA detection, HPV E6/E7 mRNA analysis, and P16INK4a and Ki-67 immunostaining. Summary estimates of sensitivity and specificity were calculated using bivariate logistic regression. Cytology was reported using the terms squamous intra-epithelial lesion (SIL) for AIN and high-grade SIL (HSIL) for high-grade AIN (HGAIN). Results. We included 22 studies. Using cytology with a cutoff of any SIL to detect HGAIN, we detected a sensitivity of 82% (95% CI, 74%–87%) and specificity of 45% (95% CI, 44%–66%); with the cutoff of HSIL, the sensitivity was 44% (95% CI, 45%–67%) and the specificity was 79% (95% CI, 69%-87%). The sensitivity of HPV DNA to detect HGAIN was 91% (95% CI, 82%–95%) and the specificity was 27% (95% CI, 21%–33%). For MSM, the positive predictive value (PPV) of cytology with a cutoff of any SIL was 36% (95% CI, 23%–50%) and the negative predictive value (NPV) was 87% (95% CI, 78%–93%), whereas cytology with a cutoff of HSIL had a PPV of 62% (95% CI, 50%–73%) and an NPV of 78% (95% CI, 65%–87%). The PPV of HR-HPV DNA detection was 37% (95% CI, 20%–57%) and the NPV was 87% (95% CI, 79%–93%). Conclusions. Given its sensitivity, cytology with a cutoff of any SIL could be considered as a triaging method, whereas cytology with a cutoff of HSIL had better specificity and could be used for quality assurance. HR-HPV DNA detection had poor specificity and PPV, making it unsuitable for triage.

AB - Background. The incidence of high-risk human papillomavirus (HR-HPV)–induced anal cancer is increasingly problematic among HIV-positive patients. Anal cancer is preceded by precursor lesions, anal intraepithelial neoplasia (AIN). AIN detection requires high-resolution anoscopy, a cumbersome and time-consuming procedure. We aggregated evidence on anal swab–based tests to detect AIN in HIV-positive patients. Methods. We searched MEDLINE and EMBASE for cross-sectional studies on AIN detection with anal cytology, HR-HPV DNA detection, HPV E6/E7 mRNA analysis, and P16INK4a and Ki-67 immunostaining. Summary estimates of sensitivity and specificity were calculated using bivariate logistic regression. Cytology was reported using the terms squamous intra-epithelial lesion (SIL) for AIN and high-grade SIL (HSIL) for high-grade AIN (HGAIN). Results. We included 22 studies. Using cytology with a cutoff of any SIL to detect HGAIN, we detected a sensitivity of 82% (95% CI, 74%–87%) and specificity of 45% (95% CI, 44%–66%); with the cutoff of HSIL, the sensitivity was 44% (95% CI, 45%–67%) and the specificity was 79% (95% CI, 69%-87%). The sensitivity of HPV DNA to detect HGAIN was 91% (95% CI, 82%–95%) and the specificity was 27% (95% CI, 21%–33%). For MSM, the positive predictive value (PPV) of cytology with a cutoff of any SIL was 36% (95% CI, 23%–50%) and the negative predictive value (NPV) was 87% (95% CI, 78%–93%), whereas cytology with a cutoff of HSIL had a PPV of 62% (95% CI, 50%–73%) and an NPV of 78% (95% CI, 65%–87%). The PPV of HR-HPV DNA detection was 37% (95% CI, 20%–57%) and the NPV was 87% (95% CI, 79%–93%). Conclusions. Given its sensitivity, cytology with a cutoff of any SIL could be considered as a triaging method, whereas cytology with a cutoff of HSIL had better specificity and could be used for quality assurance. HR-HPV DNA detection had poor specificity and PPV, making it unsuitable for triage.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85067200015&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/31123696

U2 - 10.1093/ofid/ofz191

DO - 10.1093/ofid/ofz191

M3 - Review article

VL - 6

JO - Open Forum Infectious Diseases

JF - Open Forum Infectious Diseases

SN - 2328-8957

IS - 5

ER -