Anal Cancer Screening Guidelines for PLHIV
Last updated: November 2024
Possible anal cancer screening methods
A. High risk HPV (HRHPV) testing
For cervical cancer screening, Australia and many other high-income countries have recently changed to a system which uses HPV testing as the primary screening test, because this test has a higher sensitivity than cytology. Compared with cytology testing, anal HRHPV testing has a higher sensitivity (92%) but a lower specificity (42%) for the prediction of anal HSIL31. HPV testing can be performed on the same specimen as cytology. The “technically unsatisfactory” rate is less than half that of cytology32. Extended HRHPV testing (i.e. reporting results for a range of specific HRHPV types in addition to HPV16 and HPV18) rather than partial genotyping (testing which provides results for HPV16, HPV 18 and “all other” HRPV) for PLHIV is recommended, as PLHIV have a more diverse range of causal HPV genotypes in anal cancer and a higher incidence of infections which may be transient33-34. Extended genotyping testing may reduce referral rates to HRA, by demonstrating transience for more HPV genotypes than is possible by partial genotyping. Clinicians should discuss with laboratories regarding local availability and utility of various HPV testing methods.
B. Anal Cytology
The most used screening/testing tool in countries in which ASCC screening already occurs is anal cytology, because it is relatively simple to perform, readily available and there is pre-existing laboratory expertise in the closely related field of cervical cytology. Anal cytology has a similar sensitivity to cervical cytology in the detection of the cancer precursor (81.0%), HSIL, when possible low grade squamous intraepithelial lesion (pLSIL) cytology is used as the referral threshold for referral to HRA31. However, the specificity is generally substantially lower (62.0%) than for cervical cancer screening (91.9% for a pLSIL threshold)35 and varies between different high-risk populations31. The specificity can be improved by raising the referral threshold to possible HSIL (pHSIL), but the sensitivity falls and many HSIL lesions will be missed31.
C. Performance of screening tools
A meta-analysis published in 2022 evaluated the clinical performance of cytology and HRHPV testing in detecting any HSIL in different high-risk groups, including PLHIV. The summary estimates for sensitivity and specificity of HPV testing were sensitivity 92% and specificity 42%, cytology sensitivity 81% and specificity 62% and cytology and HPV co-testing (where HPV testing and cytology are performed at the same time, and testing positive to either cytology or HPV is considered a positive result) sensitivity 93% and specificity 33%31. These results suggest no additional benefit is gained by co-testing and that specificity is adversely affected31. However, these data were not presented separately for PLHIV. These data are of limited value when determining screening test performance in non-MSM male and female populations living with HIV.
The aim of ASCC screening in PLHIV is not to identify every anal HSIL lesion. In the Study of the Prevention of Anal Cancer (SPANC), a unique natural history study of GBM with and without HIV, conducted in Sydney Australia, many anal HPV infections and HSIL were transient36. Persistence of anal HSIL is a prerequisite for invasion and for this reason, the goal of screening should be to find and treat persistent HSIL lesions.
Baseline data from the SPANC study were used to determine the ability of cytology and HPV testing to detect any HSIL in a population of GBM with and without HIV37. These data were more recently further evaluated to calculate the theoretical performance of multiple different screening methodologies in the detection of persistent HSIL38. An algorithm which used HPV as the primary screening test and cytology as a triage test for those who test HRHPV positive was developed. Those who tested HPV16 positive at baseline were referred regardless of anal cytology status. Those who had tested non16 HRHPV positive at baseline were only referred if they also had possible HSIL (pHSIL) or worse cytology at baseline, or if they had evidence of persistent non16 HRHPV infection at 12-month and had possible LSIL (pLSIL) or worse cytology at baseline. Under this scenario, the sensitivity was 95.5%, and the specificity was 49.1%, with a theoretical HRA referral rate of 59.2%38.
The IANS guidelines for ASCC screening did not recommend a particular algorithm, but recommended that acceptable screening and management strategies include:
- Digital ano-rectal examination (DARE) in everyone
- cytology alone
- HRHPV testing alone (including genotyping for HPV16)
- co-testing with cytology and HRHPV tests simultaneously
- the use of both tests, with one as the primary screening test and the other as a triage tool.
The IANS guidelines include co-testing as a screening option, despite the evidence suggesting that co-testing has no additional benefit over primary HRHPV testing31.
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