Interpreting cytology results

Abnormal findings are common on anal cytology swabs, especially in men who have sex with other men (MSM) and others who practice frequent anal intercourse. A modified Bethesda system is used to classify cytological findings. Potential results include normal, ASC-US, ASC-H (can’t rule out high grade dysplasia), LSIL, HSIL, and carcinoma. As is the case with the cervix, abnormal cytology does not always correlate with the presence of actual disease; findings must be confirmed with direct microscopic visualization of the area. To do this, we use high-resolution anoscopy (HRA), which is analogous to colposcopy for the cervix.

Because our clinic time and resources are very limited, we cannot see patients with ASC-US or LSIL results who do not have any other concerning features for high grade dysplasia or cancer. Many of these lesions represent infection with low-risk HPV types and will regress naturally over time. The future risk of developing an anal cancer with these findings is low, but not zero. Of course, many patients will be understandably concerned if they receive an “abnormal” result, even if they are still at relatively low risk of developing anal cancer.

One crucial message to impart is that anal cancer is best detected with a thorough digital ano-rectal examination. The purpose of doing anal cytology or HRA is to identify pre-cancerous lesions which may benefit from treatment or surveillance. As long as there are no palpable findings and no anal symptoms, there is no urgent need for HRA.

Clinicians offering anal cytology screening should be prepared to counsel patients regarding the management of ASC-US and LSIL results in the context of limited access to HRA. Patients who are particularly anxious may not benefit from screening if they cannot access follow-up care to further invesigate ASC-US and LSIL.

Cytology result	Interpretation
Normal	A normal anal cytology swab is reassuring. Keep in mind that cytology is not 100% sensitive, and that up to 10-15% of patients with normal results may have current HSIL. Repeating cytology and a digital exam in high risk patients on a yearly basis is worthwhile and may increase sensitivity.
ASC-US	ASC-US is a non-specific finding and not a diagnosis in and of itself; it suggests that there may be an HPV-associated lesion present, but the findings could also be due to transient inflammation. One recent study suggested that MSM with an ASCUS swab have around a 30% probability of having high grade anal dysplasia (HSIL) present when high resolution anoscopy is performed.
LSIL	LSIL usually indicates the presence of warts and/or other types of low grade dysplasia in the anus. However, around 30% of those with LSIL findings will have high grade dysplasia present.
ASC-H	ASC-H is another non-specific finding, but it does suggest a higher probability of high grade dysplasia being present, likely close to 50%.
HSIL	HSIL cytology is fairly specific for the presence of high grade dysplasia in the anus. However, the SPANC study suggested that around 20% of HSIL clears spontaneously every year, especially in younger patients. Progression from HSIL to invasive anal cancer is also not common; recent estimates suggest that the rate of malignant transformation is about 1-2% per year, though this could be slightly higher in those who are immunocompromised. The incidence of anal cancer in people under age 35 is extremely low; as such, we cannot offer ongoing follow-up for patients younger than 35 unless they are at particularly elevated risk for anal cancer.
References	Jin F et al. The performance of anal cytology as a screening test for anal HSILs in homosexual men. Cancer Cytopathology, 2016. Poynten IM et al. The Natural History of Anal High-grade Squamous Intraepithelial Lesions in Gay and Bisexual Men. Clinical Infectious Disease, 2020.

We routinely counsel patients about the following important points:

• Anal cancer is highly curable when detected early. Some patients may be candidates for a simple surgical excision, without affecting continence, and without adjuvant therapy.
• The best test to detect a current anal cancer is a regular and thorough digital ano-rectal exam (DARE), with attention paid to all quadrants of the anal canal mucosa.
• Anal paps and high resolution anoscopy are most useful to gauge a patient’s future risk of developing anal cancer, and to rule out a small focus of invasive cancer that can be treated surgically.
  

What to do with an ASC-US or LSIL result:

• Make sure you have done a DARE to rule out a palpable lesion, regardless of cytology results. Patients with palpable abnormalities can be referred to us or can be referred to a general surgeon with experience in anal cancer for biopsy/management.
• Repeat anal cytology followed by a thorough DARE every 6-12 months. Refer if cytology becomes HSIL or ASC-H (see below for caveats), or if there are any palpable abnormalities. Refer as well is there is a previous history of HSIL and the patient has not previously been assessed and discharged from an HRA program.
• If you have access to HPV-DNA testing, this can be useful to rule out high grade findings, but a positive result does not mean that there is HSIL. However, if the assay shows that HPV-16 is present, this is a higher priority for referral regardless of cytology findings as this is a particularly persistent and aggressive HPV subtype.

What to do with an ASC-H or HSIL result:

• Make sure you have done a visual inspection and DARE to rule out a visible/palpable lesion, regardless of cytology results.
• Refer for high resolution anoscopy. Younger patients at low risk for anal cancer may be offered a one-time examination to rule out prevalent cancer or aggressive HSLI and will be discharged back to your care for cytology and DARE every 6-12 months until they are eligible for further treatment.