Adenocarcinoma in Situ of the Cervix: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC
May 14, 2026

Adenocarcinoma in situ (AIS) of the cervix is a precancerous condition in which abnormal glandular cells grow in the surface lining of the cervix. These cells look like the cells seen in adenocarcinoma, a type of cervical cancer, but in AIS, the abnormal cells have not grown into the deeper layers of the cervical wall. AIS is not cancer, but it is a serious precancerous condition that can develop into invasive cancer over time if left untreated. With early detection and treatment, AIS can almost always be completely removed. This article will help you understand the findings in your pathology report — what each term means and why it matters for your care.

There are two main types of AIS. Most cases are linked to infection with high-risk human papillomavirus (HPV) and are called HPV-associated AIS. A smaller number of cases are not related to HPV and are known as HPV-independent AIS. These two types differ in their development, appearance under the microscope, detection, and management.

What causes adenocarcinoma in situ?

HPV-associated AIS results from long-term infection with high-risk HPV types — most commonly HPV16, HPV18, and HPV45. These viruses can cause abnormal changes in the glandular cells that line the inner canal of the cervix (the endocervical canal). Most people who are infected with HPV clear the virus naturally, but in some people the virus persists and can lead to precancerous conditions such as AIS. HPV-associated AIS is most often diagnosed in people in their 30s and 40s. Because it develops inside the endocervical canal — a region not always fully sampled during a routine Pap test — it can sometimes be difficult to detect through standard cervical screening.

HPV-independent AIS is a much rarer condition that is not related to HPV infection. It tends to occur in people over the age of 50 and is often detected incidentally during procedures performed for other reasons, rather than through screening. HPV-independent AIS shows what pathologists call gastric-type differentiation — meaning the abnormal cells resemble the mucus-producing cells that line the stomach rather than the normal glandular cells of the cervix. Because it is not driven by HPV, it is not detected by HPV testing, and routine screening is less effective at finding this type. The cause of HPV-independent AIS is not fully understood.

What are the symptoms?

Many people with AIS have no symptoms at all, and the condition is discovered during routine cervical cancer screening — through a Pap test, an HPV test, or both — before symptoms ever develop. This is particularly true for HPV-associated AIS.

When symptoms do occur, they may include abnormal vaginal bleeding (such as bleeding between periods or after intercourse) or an unusual vaginal discharge, which is sometimes watery or mucus-like. These symptoms are not specific to AIS and can be caused by many other, less serious conditions. HPV-independent AIS is more likely than HPV-associated AIS to produce noticeable symptoms such as a persistent watery discharge, and it can be harder to identify with a Pap test.

Because AIS can be present without causing symptoms, regular cervical screening remains the most reliable way to detect it early, before it has a chance to progress.

How is the diagnosis made?

AIS is most often first suspected when a Pap test shows atypical glandular cells — cells that look abnormal but cannot be fully classified on the Pap test alone. A positive HPV test may also prompt further investigation. When either finding is present, the next step is typically a colposcopy: an examination of the cervix using a colposcope, a special magnifying instrument that allows the doctor to look closely at its surface. During the colposcopy, a small tissue sample called a biopsy is taken from any area that looks abnormal and sent to the pathology laboratory for examination.

If a biopsy confirms AIS or if a more complete assessment of the extent of the abnormality is needed, a larger tissue removal procedure is usually performed. The two most common options are a loop electrosurgical excision procedure (LEEP) — in which a thin wire loop heated by an electric current removes a layer of tissue from the cervix — and a cone biopsy (also called conization), in which a cone-shaped portion of the cervix is removed. Both procedures include the transformation zone, the area where the outer surface of the cervix meets the inner canal and where most cervical abnormalities arise. These larger specimens provide the pathologist with more tissue to examine, allow assessment of the extent of AIS, and help determine whether any invasive cancer is also present.

Under the microscope, the pathologist confirms AIS by identifying abnormal glandular cells that remain confined to the surface lining of the cervix, with no evidence of invasion into the deeper cervical wall. To confirm the diagnosis and distinguish the two types of AIS, additional special tests are often performed. In HPV-associated AIS, a protein stain called p16 — a marker produced in large amounts by cells driven by high-risk HPV — typically shows strong, continuous staining throughout the abnormal cells. This distinctive staining pattern, called block-type positivity, strongly supports the diagnosis. A Ki-67 stain is also frequently performed; elevated Ki-67 reflects a high rate of cell division, which is characteristic of AIS. In HPV-independent AIS, p16 staining is typically absent or patchy, and other specialized stains — including MUC6 and HIK1083 — may be used to confirm the gastric-type features. When the diagnosis is uncertain, a test called in situ hybridization (ISH) can detect HPV genetic material directly inside the cells, confirming whether the abnormal cells are HPV-driven.

What does adenocarcinoma in situ look like under the microscope?

Under the microscope, AIS shows abnormal glandular cells that are still confined to the surface lining of the cervix and have not grown into the deeper layers of the cervical wall. The microscopic features differ between the two main types.

In HPV-associated AIS, the abnormal cells are tall and column-shaped. They are typically crowded together, and they produce little or no mucin (the thick, gel-like substance that normal cervical glandular cells secrete). The nuclei — the structures inside the cells that contain the genetic material — are dark, elongated, and stacked in layers. The pathologist usually sees many actively dividing cells, visible as mitotic figures, and some cells show fragmentation called karyorrhexis. The abnormal cells generally follow the outline of the normal glands but may also form more complex patterns, including cribriform (sieve-like) arrangements or papillary (finger-like) projections.

In HPV-independent AIS (gastric type), the cells tend to be cube-shaped or column-shaped with pale or foamy-looking cytoplasm (the material surrounding the nucleus) that is often filled with mucin. The nuclei are enlarged and irregular but typically show less active division than in HPV-associated AIS. The abnormal cells stay within the outlines of the normal glands, though they may form slightly more complex arrangements. Intestinal-type features, including cells with distinctive mucus-filled vacuoles called goblet cells, are sometimes also seen.

Surgical margins

A margin is the edge of the tissue that was removed during the excision procedure. After surgery, the pathologist examines the margins under the microscope to determine whether any AIS cells are present at the cut edges. Margins are reported only in excision specimens — such as a LEEP or cone biopsy — and not in Pap tests or small biopsies, which are not intended to remove the entire lesion. The margin result is one of the most important factors in guiding your care after treatment.

Negative margin — No AIS cells are present at the cut edge of the tissue. This is the most reassuring result and suggests the abnormal tissue was completely removed.
Positive margin — AIS cells are present at the cut edge. This means some abnormal cells may remain in the cervix, increasing the risk that AIS could recur or progress. Additional surgery or closer follow-up is typically recommended.

Three margin locations are assessed in cervical excision specimens:

Endocervical margin — The inner edge of the specimen, closest to the uterus. Involvement of this margin is particularly significant because it indicates that abnormal cells may remain high in the endocervical canal, where they are difficult to detect on follow-up screening.
Ectocervical margin — The outer edge of the specimen, closest to the vagina.
Stromal margin — The deep edge, corresponding to the wall of the cervix beneath the removed tissue.

What is the prognosis for adenocarcinoma in situ?

With appropriate treatment, the prognosis for AIS is excellent in most cases. The most important factor in predicting outcome is whether the abnormal tissue has been completely removed. Several features from the pathology report influence the likelihood of recurrence or progression to cancer:

Negative surgical margins — When the margins of the excision are free of AIS, the recurrence rate after cone biopsy is low, generally in the range of 2 to 5%. Hysterectomy (removal of the uterus and cervix) is essentially curative for HPV-associated AIS.
Positive surgical margins — When AIS cells are present at the cut edge of the tissue, the risk of residual disease and recurrence increases substantially, to approximately 15-20%. Repeat excision or more frequent surveillance is usually recommended.
HPV-associated vs. HPV-independent type — HPV-associated AIS responds well to excision with clear margins and carries a favorable overall outcome. HPV-independent (gastric-type) AIS has a significantly less favorable prognosis: it is associated with a higher risk of progressing to invasive adenocarcinoma, and these cancers tend to behave in a more serious way. Because of this, more definitive surgery, such as a hysterectomy, is often recommended even when the surgical margins appear clear.
Persistent HPV infection — For people who are managed with conservative, fertility-preserving surgery for HPV-associated AIS, persistent HPV infection after treatment is a recognized risk factor for recurrence and requires ongoing close monitoring.

What happens after this diagnosis?

Treatment is almost always recommended for AIS because the condition carries a meaningful risk of progressing to invasive cervical cancer if it is not completely removed. The choice of treatment depends on the type of AIS, the surgical margin status, your age, and whether you wish to preserve the ability to have children in the future.

For women who wish to preserve fertility, a cone biopsy or LEEP with negative margins may be offered as initial treatment. This fertility-preserving approach requires close surveillance with repeat Pap tests and HPV testing — typically every six months for at least two years — to monitor for any signs that AIS has returned. If margins are positive or the lesion is extensive, a repeat excision may be needed to achieve clear margins before continuing with surveillance alone.

For women who have completed having children or who have HPV-independent AIS, a simple hysterectomy (removal of the uterus and cervix) is often recommended. This eliminates the risk of recurrence from any residual abnormal tissue in the cervix and is considered definitive treatment for HPV-associated AIS.

After any treatment, regular follow-up is essential. Your doctor or gynecologic oncologist will guide the timing and type of follow-up testing based on your pathology results, margin status, HPV test results, and type of AIS.

Questions to ask your doctor

Is my AIS the HPV-associated type or the HPV-independent type, and how does that affect my treatment options?
Were my surgical margins negative, and does that mean all of the abnormal tissue was removed?
If my margins are positive, what is the next recommended step — repeat surgery or closer surveillance?
Was any invasive cancer found in my specimen, or is the diagnosis purely AIS?
What are my treatment options, and which would you recommend based on my specific pathology results?
I want to preserve my fertility — is conservative surgery a safe option for my situation?
What will my follow-up schedule look like, and what tests will be used to monitor me?
How long will I need regular follow-up testing, and at what point would I return to routine screening?
Was p16 staining performed on my specimen, and what did the result show?
What is the difference between a LEEP and a cone biopsy, and which is more appropriate for me?
If I have HPV-independent AIS, does that change the recommended treatment approach compared to HPV-associated AIS?
What symptoms should prompt me to contact you between scheduled follow-up appointments?