Introduction
Populations | Annual incidence of anal cancer (per 100,000) |
---|---|
People living with HIV | |
Men who have sex with men (MSM)* | 85 |
< 30 years old | 17 |
Between 30 and 45 years old* | > 60 |
> 45 years old* | ≥ 100 |
Men who have sex with women | 32 |
Women | 22 |
MSM without HIV | 19 |
Solid organ transplant patients (transplantation > 10 years ago) | |
Men | 24.5 |
Women* | 50 |
Women with a history of HPV-related precancerous lesions/gynecological cancers | |
Precancerous lesions of the cervix (CIN2 and more) | 6 |
Cervical cancer | 9 |
Precancerous lesions of the vagina (VAIN3) | 19 |
Vaginal cancer | 10 |
Precancerous lesions of the vulva (VIN3)* | 42 |
Vulvar cancer* | 45 |
History of autoimmune disease | |
Systemic lupus erythematosus | 10 |
Ulcerative colitis | 6 |
Crohn’s disease | 3 |
Methods
Screening for precancerous anal lesions
Objectives of screening
The treatment of high-grade precancerous lesions (HSILs) decreases the risk of progression to SCC. Grade A |
Screening for precancerous anal lesions facilitates the early diagnosis of SCC, suggesting a possibility for increasing survival. Grade C |
Screening methods
Standard proctological examination
1. Conditions for performing the SPE |
Symptoms, such as anal pain, swelling, and bleeding, should be checked for during the interview and, if present, a proctological examination should be performed by a gastroenterologist/proctologist. Grade C |
Examinations of the anal margin and digital anorectal examinations can be performed by any doctor. Grade C |
The training of patients/their partners and doctors who are not proctologists in screening makes it possible to increase the dissemination, implementation, and performance of screening. Grade B |
Any gastroenterologist in France should be able to perform a complete proctological examination with standard anoscopy. Training in how to perform this examination and in screening for anal cancer should be an integral component of both initial and on-the-job training. Expert agreement |
Anorectal and complete proctological examinations are rapid, cheap, and well accepted by patients. Grade C |
Warts are mostly lesions without dysplasia or with low-grade dysplasia because they are linked to low-risk HPV. HSILs visible to the naked eye have a variable macroscopic appearance in terms of size, color, and shape. Any suspicious lesions should be biopsied to check for invasive SCC. Grade C |
The benefit of acetic acid during a standard proctological examination has not been demonstrated. Grade C |
Collaboration between the doctors following the populations at risk of anal cancer and gastroenterologists/proctologists must be strengthened. Each care center should define a referent proctologist if possible. Expert agreement |
2. Diagnostic performance |
Detecting anal cancers at an early stage is an important goal of screening. Grade B |
Examination of the anal margin and digital anorectal examination can detect cancers of the anus at an early stage. Grade B |
A complete proctological examination with standard anoscopy can detect warts, macroscopically visible HSILs, and anal cancers at an early stage. Grade C |
Screening strategies should take the availability of different screening tools into account. Grade C |
3. Strategic limitations |
The benefit of standard anoscopy-based screening for decreasing the incidence of anal cancer has not yet been demonstrated. Grade B |
HSILs cannot be diagnosed by digital anorectal examination. Grade A |
Clinical examination with standard anoscopy has low sensitivity for the diagnosis of HSIL. Less than 40% of HSILs are visible to the naked eye. Grade A |
Anal cytology
1. Conditions for performing anal cytology screening |
Anal cytology screening should be performed in target populations. Grade A |
The evidence for benefits of proctological screening is better for PLHIV aged ≥ 35 years. Grade A |
There are insufficient data to determine the exact rate at which surveillance by anal cytology should be performed. Grade C |
2. Diagnostic performance |
Anal cytology is twice as sensitive as clinical examination for the detection of HSILs. Grade B. However, its specificity is limited. Grade A |
The grade of cytological abnormalities is poorly correlated with the grade of histological abnormalities. Grade B |
The anal cytology screening strategy is indicated for high-risk populations at expert centers, but the sensitivity and specificity of the test are insufficient to justify its use for mass screening. Grade B |
A complete strategy, defined as a combination of standard anoscopy, anal cytology, and HPV16 detection, provides higher detection rates for HSILs. Grade B |
Most international recommendations are based on the performance of an anal smear followed by HRA if an abnormality is found. Such strategies have been the most studied, but possible association with an HPV test could lead to their evolution. Grade C |
3. Strategic limitations |
Anal cytology is of marked interest in the absence of visible lesions on clinical examination. In cases of macroscopic lesions, targeted biopsies are indicated for histological analysis. Grade B |
Anal cytology has a high sensitivity but a low specificity, leading to the risk of performing “unnecessary” HRA. Grade A |
HRA must be performed at an expert center in the event of abnormal cytological results for patients from populations at a high risk of cancer. Grade B |
If HRA is unavailable, the goal of screening should be the early diagnosis of anal cancer and macroscopic HSILs. Expert agreement |
HR-HPV screening
1. Conditions for HR-HPV testing |
The entire anal canal should be swabbed, especially the anorectal transformation zone. Grade B |
The storage of samples collected for virological purposes in a liquid cytology medium makes it possible to perform anal cytology on the same sample. Grade A |
The diagnostic performance of self-sampling has yet to be assessed. Grade C |
2. Diagnostic performance |
For patients at risk, HR-HPV testing is sensitive, but not very specific for the diagnosis of HSIL, due to a high prevalence of anal HR-HPV infection. Grade A |
In the event of a positive HR-HPV test, a specific triage test should be considered. Grade C |
The combination of HPV testing and anal cytology improves diagnostic performance. Grade A |
The restriction of testing to HPV16 improves specificity but decreases sensitivity for the diagnosis of HSIL. Grade A |
In the absence of anal HR-HPV infection, the probability of developing HSIL lesions within 5 years is low. Grade B |
3. Strategic limitations |
In addition to detecting HR-HPV infection, the persistence of this infection must be evaluated. Grade C |
The presence of HPV16 is a risk factor for the progression of HSILs to cancer. However, limiting testing to HPV16 markedly decreases the sensitivity of the test for HSIL diagnosis. Grade B |
In France, tests for HR-HPV in anal swabs are not reimbursed |
High-resolution anoscopy
1. Conditions for performing HRA |
HRA is a second-line screening tool. It is performed after an abnormal triage test result, usually following an abnormal anal cytology result. Grade B |
HRA is also used for the targeted treatment and monitoring of HSILs. Grade B |
A diagnosis of HSIL is suspected in patients with a combination of staining abnormalities, abnormal vessels, and epithelial changes. Histological confirmation should systematically be sought. Grade B |
The quality criteria for this examination are the subject of recommendations from the International Anal Neoplasia Society (IANS). Expert agreement |
Practitioners should perform at least 50 HRAs per year. Grade C |
2. Diagnostic performance |
HRA is the gold standard for the detection, targeted treatment, and monitoring of HSILs. Grade B |
HRA outperforms clinical examination with standard anoscopy for the diagnosis of HSIL. Grade B |
It is recommended to ensure that a detection rate for high-grade lesions of 90% is obtained for patients with an HSIL-positive smear in the preceding 3 months. Grade C |
Due to the poor correlation between anal cytology and histology results, a non-negligible proportion of patients (> 10%) with an ASC-US+ or LSIL smear have high-grade HRA lesions. Grade B |
3. Strategic limitations |
The natural course of high-grade lesions visible only by HRA is unknown. Expert agreement |
The long learning curve and poor availability of this examination currently limit access to this technique. Expert agreement |
HRA should be performed by clinicians who have received appropriate training. Grade B |
When available, HRA should be offered to “at-risk” patients. The efficacy of strategies including HRA has been evaluated principally in MSM patients living with HIV. Grade B |
The benefit of HRA for decreasing the incidence of anal cancer has yet to be demonstrated. Grade B |
Other biomarkers
The objective of biomarker use is to improve the specificity of anal cytology and the detection of HR-HPV. Grade B |
P16/Ki-67 dual-staining |
1. Conditions for performing p16/Ki-67 dual-staining |
Dual-staining for p16/Ki-67 can be performed on cytological or histological samples |
2. Diagnostic performance |
The p16 marker can be used to differentiate LSIL from HSIL histologically. Grade A |
The diagnostic performance of dual-staining for p16 and Ki-67 in immunocytochemistry is not superior to that of cytology alone for the diagnosis of HSIL. Grade C |
p16/Ki-67 dual-staining is less sensitive but more specific than testing for HR-HPV for the diagnosis of HSIL. Grade C |
3. Strategic limitations |
The diagnostic value of dual p16/Ki-67 dual-staining alone or in combination with anal cytology has not been demonstrated. Grade C |
Staining for p16 may be of prognostic value but this requires confirmation. Grade C |
Methylation |
1. Conditions for methylation marker use |
Methylation markers can be analyzed on cytological or histological samples |
2. Diagnostic performance |
It is not possible to assess the diagnostic performance of methylation markers on the basis of the data currently published. Grade C |
Methylation markers may be of prognostic value for predicting the progression of HSIL to cancer. Expert agreement |
3. Strategic limitations |
The diagnostic and prognostic values of methylation markers have yet to be demonstrated. Studies are underway. Grade C |
E6/E7 mRNA |
1. Conditions for E6/E7 mRNA use |
The presence of mRNA encoding the E6/E7 oncoproteins is a sign of active HR-HPV infection |
These transcripts are sought in cytological samples |
2. Diagnostic performance |
The diagnostic performance of testing for the presence of E6/E7 mRNA is not superior to cytology alone for the diagnosis of HSIL. Grade C |
3. Strategic limitations |
The diagnostic value of testing for the presence of E6/E7 mRNA alone or in combination with anal cytology has not been demonstrated. Grade C |
Algorithm
1. Usable strategies and diagnostic performance |
The most widely used triage tests are virological tests to detect HR-HPV and liquid-phase anal cytology. The first of these methods is the most sensitive (4% false negatives) and the second is the most specific (64% true positives in the presence of HSIL). The use of these two tests is recommended in patients with risk factors for dysplasia and cancer. Grade A |
In theory, initial use of an HPV test (with HPV16 genotyping) could be preferred, with positive results leading to the performance of anal cytology. Grade B |
Other specific tests have not been adequately studied and cannot yet be recommended in routine practice. Grade B |
2. Strategic limitations |
Given the intercenter and interobserver variability of the diagnosis of anal dysplasia, it is recommended that the practitioners and pathologists responsible for making positive diagnoses of dysplasia undergo prior training and compare their diagnostic performances. Grade B |
The testing of screening protocols in real-life conditions is recommended, to analyze the compliance of at-risk individuals and the conditions for reimbursement of the tests. Grade C |
Within the framework of screening for the early diagnosis and monitoring of lesions of dysplasia, the management and reimbursement of virological tests and cytological analyses by public authorities is important, as is the specific consideration of HRA |