Anal Dysplasia

Anal dysplasia is another term for abnormal changes that can be found in the anal canal.  All warts have some abnormal changes seen by the pathologist when they look at the removed wart under the microscope.  The pathologist will grade the changes as low-grade and high-grade anal intra-epithelial neoplasia. Cells labeled as high-grade anal intraepithelial neoplasia are considered “premalignant,” but have not invaded deeper into the skin. While this condition is likely a precursor to anal cancer, this is not anal cancer and is treated differently than anal cancer.  Thus, patients with anal dysplasia need close follow-up determined by their physician and any new lesions must be evaluated promptly. A gynecologic examination is also recommended in females, as the presence of high-grade anal intra-epithelial neoplasia puts a female patient at risk for having CIN.

What causes anal dysplasia?
Anal dysplasia is similar to cervical dysplasia (cervical intraepithelial neoplasia or CIN) in that it originates from a human papilloma virus (HPV) infection and can develop into anal and cervical cancer, respectively.

Who is at increased risk for anal dysplasia?
Risk factors for anal dysplasia include:

1.     History of known HPV infections (most common)

2.     History of anal intercourse (men and women, regardless of sexual orientation)

3.     Positive HIV test

4.     Cigarette smoking

5.     Immune-deficiency states from certain medications (solid organ transplantation, RA, IBD)  

Why do we need to treat anal dysplasia?
Once you have anal dysplasia, it rarely disappears.  Although still exceedingly uncommon, there is a slight increased risk of anal cancer in patients with a history of anal dysplasia (less than 5%). Its progression in HIV-positive patients seems to be higher.

How is anal dysplasia diagnosed?
Anal dysplasia can be found incidentally at the time of unrelated anal surgery (i.e., hemorrhoid surgery). However, all patients, regardless of gender or sexual orientation, with risk-factors such as a previous positive cervical Papanicolaou (pap) smear, known history of HPV infection, or history of anal-receptive intercourse, should have a screening anal pap smear.

What is an Anal Papanicolaou (pap) Smear?
An anal Papanicolaou (Pap) smear cytology consists of using anal swabs to obtain a sampling of cells from the anal canal and can be used for both screening patients considered high-risk (see list above) and as followup after anal dysplasia has been treated.  Up to 45% of patients can have a false-positive test by anal pap for anal dysplasia.  The results of anal pap smears can be negative (normal), atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intra-epithelial lesion (LSIL) or high-grade squamous intra-epithelial lesion (HSIL).

How is anal dysplasia treated? 

Observation alone with close clinical follow-up may be indicated for certain abnormal Pap smear results.  There is a high risk of recurrence following treatments, so physicians may recommend close observation and physical examination every 3 to 6 months depending on risk factors, which strains of HPV are involved, and the Pap smear results.    However, due to the high risk of also having cervical dysplasia, a referral to gynecology is recommended.

Topical 5% imiquimod (Aldara) cream or 5% 5-fluorouracil (5-FU) cream may be applied to areas of anal dysplasia. Local treatment creams may be needed for 9 to 16 weeks. Up to 90% may have anal lesions disappear, although as many as 50% can recur.  Local side effects are very common, occurring in up to 85%, and include skin irritation and hypo-pigmentation (loss of color around the anus), but these stop or reverse after cream treatment ends.

High Resolution Anoscopy (HRA) typically involves the application of temporary stains (3% acetic acid and Lugol’s iodine solution) to the anal canal followed by evaluation under high-resolution microscopy to help differentiate normal from abnormal tissue. This is very similar to colposcopy (examination of the cervix) in women who have cervical dysplasia and can be done as an office procedure. Directed biopsies and local destruction are performed for any questionable areas and to identify areas that may need further treatment. Photodynamic therapy or infra-red coagulation may be used in select patients. Similar to use in other types of skin cancers, photodynamic therapy has been described in patients with anal dysplasia since 1992. In the event there are larger areas in need of intervention, high resolution anoscopy can be done in the operating room on a larger scale than can be reasonably performed in the office setting.

Surgery
A variety of surgical techniques to remove anal dysplasia have been used to prevent disease progression. These include wide local excision and targeted therapy using high-resolution anoscopy (HRA).  Wide local excision’s goal is to remove all of the affected areas with normal surrounding tissue (“negative margins”), although total removal of all disease is often difficult.  Sometimes a local flap of normal tissue adjacent to the removed area is used to cover a large defect.  There is still a high rate of recurrence of anal dysplasia despite a wide removal of tissue and high rates of complications such as stenosis anal (narrowing of the area) and fecal incontinence. Targeted destruction guided by high-resolution anoscopy is effective to identify, biopsy and destroy anal dysplasia without the long recovery and complications associated with wide local excision.  However, there is still a high risk of persistent or recurrent disease, reported in up to 20 to 80%.  Surgical complications such as incontinence and stenosis are generally not seen with HRA, though.  Fortunately, both wide local excision and targeted destruction by HRA have been shown to prevent progression from anal dysplasia to anal cancer.

How should patients be followed after treatment for anal dysplasia?
Patients with anal dysplasia should usually be closely followed long term to detect recurrence, persistence or progression to anal cancer.  Physical examinations may be performed at 3- to 6-month intervals. This approach allows for the treatment of recurrent or persistent dysplasia or the detection of anal cancer.  Followup generally may include:

  • Digital rectal examination,
  • Anoscopy,
  • Anal Pap smear
  • High resolution anoscopy (HRA).

The importance of close followup cannot be over emphasized in patients with history of anal dysplasia, especially if new lesions develop.