HPV Associated Adenocarcinoma of the Cervix: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC
May 14, 2026

HPV-associated adenocarcinoma is a type of cervical cancer that develops from the glandular cells lining the inside of the cervix. These cells normally produce mucus and form the lining of the cervical canal, the passageway connecting the uterus to the vagina. HPV-associated adenocarcinoma is caused by persistent infection with high-risk human papillomavirus (HPV) types, particularly HPV18, HPV16, and HPV45. Most HPV-associated adenocarcinomas arise in the transformation zone, the area where glandular cells inside the cervix meet squamous cells on the outer surface.

Compared with HPV-independent forms of cervical adenocarcinoma, HPV-associated adenocarcinomas tend to occur at a younger age and generally have a better outlook. This article will help you understand the findings in your pathology report, what each term means, and why it matters for your care.

What causes HPV-associated adenocarcinoma?

HPV-associated adenocarcinoma is caused by persistent infection with high-risk types of HPV. HPV is a very common virus that spreads through skin-to-skin contact, including sexual contact. Most HPV infections are cleared by the immune system within one to two years and never cause any lasting changes. In a small percentage of people, however, the infection persists. The high-risk types most often linked to cervical adenocarcinoma are HPV18, HPV16, and HPV45. Notably, HPV18 plays a larger role in cervical adenocarcinoma than it does in cervical squamous cell carcinoma.

When the virus persists, viral proteins interfere with the systems that normally regulate cell growth and division, leading to abnormal growth of glandular cells. Over time, this process can progress through a precancerous stage called adenocarcinoma in situ (AIS) and eventually become invasive cancer. Additional genetic changes accumulate as the tumor develops, contributing to abnormal cell growth and survival.

Several factors influence the likelihood that an HPV infection will persist and lead to adenocarcinoma:

Persistent high-risk HPV infection — The single most important risk factor. Infections that last for many years carry the highest risk.
A weakened immune system — Conditions such as HIV infection, organ transplantation, or long-term immunosuppressive therapy make it harder for the body to clear the virus.
Long-term use of oral contraceptives — Has been associated with an increased risk of cervical adenocarcinoma in epidemiologic studies, although the absolute increase in risk is modest.
Cigarette smoking — Has a smaller effect on adenocarcinoma than on squamous cell carcinoma but is still associated with increased risk.
Lack of regular cervical cancer screening — Because adenocarcinoma arises inside the cervical canal, where it can be difficult to sample with a Pap test, regular screening with combined Pap and HPV testing is particularly important for early detection.

What are the symptoms?

The symptoms of HPV-associated adenocarcinoma vary. Some patients have no symptoms at all and are diagnosed only because of an abnormal cervical screening result. When symptoms do occur, the most common is abnormal vaginal bleeding, such as bleeding after intercourse, between menstrual periods, or after menopause. Some patients notice an unusual vaginal discharge, which may be watery, mucus-like, or tinged with blood. Pelvic pain is less common and tends to occur with more advanced disease.

Because HPV-associated adenocarcinoma can grow inside the cervical canal, where it may not produce noticeable symptoms until it is more advanced, regular cervical screening with Pap testing and HPV testing remains the most reliable way to find it early.

How is the diagnosis made?

The diagnosis of HPV-associated adenocarcinoma usually begins with an abnormal cervical screening result, such as atypical glandular cells on a Pap test or a positive HPV test for high-risk types. The next step is typically a colposcopy, an examination of the cervix using a colposcope, a special magnifying instrument that allows the doctor to inspect the surface of the cervix in detail. During colposcopy, a small tissue sample called a biopsy is taken from any abnormal area and sent to the laboratory. A separate sample may also be collected from inside the cervical canal using a procedure called endocervical curettage, because adenocarcinoma often arises higher in the canal where it cannot be fully seen with the colposcope.

If a biopsy confirms cancer, or if a more complete assessment is needed, a larger tissue specimen is usually obtained through a cone biopsy or a loop electrosurgical excision procedure (LEEP). If surgery to treat the cancer is performed, the pathologist examines the removed tissue to determine the size of the tumor, how deeply it has grown into the cervix, whether it has spread to nearby structures, the status of the surgical margins, and whether any lymph nodes contain cancer.

To confirm the diagnosis and distinguish HPV-associated adenocarcinoma from other glandular cancers that can occur in the cervix and uterus, the pathologist performs several special tests. A protein called p16, detected by immunohistochemistry, almost always shows strong, continuous “block-type” staining throughout the tumor because cells driven by high-risk HPV produce large amounts of this protein. Strong p16 staining is one of the most important features supporting an HPV-associated cause. Stains called CK7 and PAX8 typically come back positive and support a cervical origin for the tumor. The tumor cells are usually negative for estrogen receptor (ER), progesterone receptor (PR), and vimentin, which helps distinguish HPV-associated cervical adenocarcinoma from endometrial adenocarcinoma. The tumor also usually shows a wild-type p53 staining pattern, which helps distinguish it from HPV-independent gastric-type adenocarcinoma, which often shows an abnormal p53 pattern. When the diagnosis is uncertain, a test called in situ hybridization (ISH) can detect HPV genetic material directly within the tumor cells and confirm the HPV-driven nature of the cancer. Tests that detect HPV RNA are generally more specific than tests that detect HPV DNA.

What does HPV-associated adenocarcinoma look like under the microscope?

Under the microscope, HPV-associated adenocarcinoma is made up of abnormal glandular cells that form irregular glands and invade the supporting tissue of the cervix. The tumor cells typically have enlarged, elongated nuclei that appear darker than normal and may contain visible nucleoli (small structures inside the nucleus where ribosomes are made). The glands are often lined by tall, column-shaped cells that produce some mucus.

A characteristic feature that helps the pathologist recognize HPV-associated adenocarcinoma is the presence of mitotic figures (dividing cells) and apoptotic cells (cells undergoing programmed death) near the surface of the glands, often visible even at low magnification. Some tumors grow in a destructive pattern, with irregular glands and small clusters of cancer cells infiltrating the cervical tissue and producing a dense fibrous reaction called desmoplasia. Other tumors grow in a less destructive pattern, with well-formed glands that resemble adenocarcinoma in situ but also show invasion into the underlying tissue. These different growth patterns are formally described using the Silva pattern classification, which is discussed in its own section below.

Silva pattern classification

HPV-associated adenocarcinoma can grow into the surrounding tissue in different ways. The Silva pattern classification describes these growth patterns and helps estimate the likelihood that the cancer will spread to lymph nodes or recur after treatment. The classification divides tumors into three patterns based on how the cancer invades the cervical tissue:

Pattern A — The cancer forms well-defined glands that remain closely grouped and grow into the cervical tissue without destructive invasion. Cancer cells are not seen inside blood vessels or lymphatic vessels. Pattern A tumors carry a very low risk of spreading to lymph nodes or recurring after treatment.
Pattern B — Small groups of cancer cells begin to break away from the main glands and invade the surrounding tissue in limited areas. Some Pattern B tumors show lymphovascular invasion. The risk of lymph node spread and recurrence is higher than for Pattern A but still relatively low.
Pattern C — The cancer shows diffuse, destructive invasion into the surrounding tissue. The glands are often irregular and distorted, and the nearby tissue frequently shows a fibrous reaction. Pattern C tumors are most likely to show lymphovascular invasion and to spread to lymph nodes, and they have the highest risk of recurrence.

The Silva pattern classification has emerged as an important prognostic tool for HPV-associated cervical adenocarcinoma. Tumors with Pattern A behavior may be candidates for less extensive surgery, while tumors with Pattern B or Pattern C may prompt the team to consider more extensive surgery and adjuvant treatment. Your pathology report may name the Silva pattern directly or describe the invasion pattern in narrative form.

Silva patterns

Tumor size and depth of invasion

Once invasive cancer is confirmed, the pathologist measures the tumor to determine its size and how deeply it has grown into the cervix. Tumor size describes the largest dimension of the cancer along the surface of the cervix and is usually reported in centimeters. Depth of invasion describes how far the tumor has grown from the surface lining into the supporting tissue (the stroma) of the cervix and is usually reported in millimeters.

Both measurements are important because larger tumors and those that invade more deeply are more likely to spread to lymph nodes or nearby organs, and they carry a higher risk of recurrence. These measurements also determine the tumor stage (see the staging section below) and influence which surgical and other treatment options the gynecologic team will discuss with the patient.

Lymphovascular invasion

Lymphovascular invasion means that tumor cells are seen inside small lymphatic channels or blood vessels in the cervix. These vessels normally carry fluid or blood through the body. When tumor cells gain access to these channels, they can travel to nearby lymph nodes or distant organs. The presence of lymphovascular invasion is an adverse feature, as it indicates an increased risk that the cancer has already begun to spread and may influence decisions about surgery and the use of additional treatment after surgery.

Perineural invasion

Perineural invasion means that tumor cells are growing along or around nerves in the cervix. This pattern of growth allows the cancer to extend along nerves into the surrounding tissue and is associated with a higher risk of local recurrence after treatment. The presence of perineural invasion may lead the team to consider additional radiation therapy after surgery.

Surgical margins

A margin is the cut edge of tissue removed during a surgical procedure such as a cone biopsy or hysterectomy. After surgery, the pathologist examines the margins under the microscope to determine whether any cancer cells are present at the cut edges.

Negative margin — No cancer cells are present at the cut edge of the tissue. This suggests that the entire tumor was removed, and this is the most reassuring result.
Close margin — Cancer cells are within a few millimeters of the cut edge but not reaching it. A close margin may prompt the team to consider additional treatment, depending on the rest of the pathology findings.
Positive margin — Cancer cells extend to the cut edge of the tissue. This means some cancer cells may still remain in the cervix or surrounding tissue and increases the risk of recurrence. Positive margins may lead the team to discuss further surgery or postoperative radiation.

Lymph nodes

Lymph nodes are small immune organs that filter fluid as it returns from the body’s tissues to the bloodstream. The cervix drains into lymph nodes in the pelvis, and from there to lymph nodes higher in the abdomen along the aorta (the para-aortic nodes). During surgery for cervical cancer, lymph nodes from these areas may be removed and examined under the microscope.

If tumor cells are found inside a lymph node, the cancer is considered to have spread beyond the cervix, and the pathologic stage is increased. The pathology report describes the number of lymph nodes examined, the number that contain tumor cells, the location of the involved nodes, and the size of the tumor deposit in each node:

Isolated tumor cells — Tiny clusters measuring 0.2 mm or less.
Micrometastases — Tumor deposits larger than 0.2 mm but no larger than 2 mm.
Macrometastases — Tumor deposits larger than 2 mm.

Larger deposits and a greater number of involved nodes are associated with a worse prognosis and may influence the choice and intensity of additional treatment.

Biomarker and molecular testing

Biomarker testing examines proteins or other molecular features in the tumor to guide treatment decisions. Not every biomarker is tested in every case. Testing is typically performed when the cancer is advanced, recurrent, or metastatic, and the results help determine eligibility for specific therapies.

PD-L1

PD-L1 is a protein that some tumor cells use to evade immune system detection. Testing for PD-L1 is performed by immunohistochemistry on a tumor sample and is reported as the Combined Positive Score (CPS), which reflects PD-L1 expression on tumor cells and on nearby immune cells. For cervical cancer, a CPS of 1 or higher is the threshold that indicates eligibility for immune checkpoint inhibitor therapy with pembrolizumab in advanced, recurrent, or metastatic disease. A PD-L1 result on the pathology report does not, by itself, dictate treatment; instead, it informs the discussion the medical oncology team has with the patient about whether immunotherapy is an appropriate option.

Pathologic stage

Staging describes how far the cancer has spread within the cervix and beyond. Stage is one of the most important factors in predicting outcome and in shaping the decisions made by the gynecologic and medical oncology teams about further treatment. Cervical cancer is staged using two related systems: the AJCC pTNM system (currently AJCC 8th edition) and the FIGO system (currently the FIGO 2018 revision, which remains in effect). The two systems are aligned and use the same anatomic categories, but FIGO is more commonly used by gynecologic oncologists for treatment planning.

The TNM system describes the size and extent of the tumor in the cervix (T), whether nearby lymph nodes contain cancer (N), and whether the cancer has spread to distant organs (M). The metastasis category (M) is generally determined by imaging studies rather than by examination of the surgical specimen.

Tumor stage (pT)

pT1 — Tumor confined to the cervix.
- pT1a — Invasive cancer that can be identified only under the microscope, with a depth of invasion of 5 mm or less. (FIGO 2018 removed the prior 7 mm horizontal width criterion, so T1a is now defined by depth alone.)
  - pT1a1 — Depth of invasion 3 mm or less.
  - pT1a2 — Depth of invasion greater than 3 mm but no more than 5 mm.
- pT1b — Invasive cancer with depth of invasion greater than 5 mm, still confined to the cervix.
  - pT1b1 — Tumor 2 cm or less in greatest dimension.
  - pT1b2 — Tumor greater than 2 cm but no more than 4 cm.
  - pT1b3 — Tumor greater than 4 cm.
pT2 — Tumor extends beyond the cervix but has not reached the pelvic wall or the lower third of the vagina.
- pT2a — Tumor involves the upper two-thirds of the vagina but not the parametrium (the fibrous tissue beside the cervix). Subdivided into pT2a1 (4 cm or less) and pT2a2 (greater than 4 cm).
- pT2b — Tumor has invaded the parametrium.
pT3 — Tumor involves the lower third of the vagina, reaches the pelvic wall, or causes blockage of a ureter (which can damage the kidney).
- pT3a — Tumor involves the lower third of the vagina, without extension to the pelvic wall.
- pT3b — Tumor extends to the pelvic wall, blocks a ureter, or both.
pT4 — Tumor has grown into the lining of the bladder or rectum, or has extended beyond the pelvis.

Nodal stage (pN)

pNX — Regional lymph nodes were not examined.
pN0 — No cancer found in the examined regional lymph nodes.
pN0(i+) — Only isolated tumor cells (clusters 0.2 mm or smaller) are present in regional lymph nodes.
pN1 — Larger tumor deposits are present in regional lymph nodes.
- pN1a — Metastasis to pelvic lymph nodes only.
- pN1b — Metastasis to para-aortic lymph nodes, with or without pelvic lymph node involvement.

Metastatic stage (pM)

The metastasis category is determined by imaging studies and clinical evaluation rather than by examination of the surgical specimen. pM0 means no distant spread has been identified; pM1 means cancer has spread to distant organs such as the lungs, liver, or bones.

FIGO stage

The FIGO stage is reported alongside the TNM stage. It reflects the combined pathologic and imaging findings and is the system most commonly used to guide treatment planning:

Stage I — Cancer confined to the cervix. Subdivided into IA1, IA2, IB1, IB2, and IB3 using the same depth and size cut-offs as the AJCC pT1 categories above.
Stage II — Cancer has spread beyond the cervix but has not reached the pelvic wall or the lower third of the vagina. Subdivided into IIA1 (upper vagina, 4 cm or less), IIA2 (upper vagina, greater than 4 cm), and IIB (parametrial invasion).
Stage III — More extensive spread.
- Stage IIIA — Cancer involves the lower third of the vagina.
- Stage IIIB — Cancer reaches the pelvic wall or blocks a ureter.
- Stage IIIC1 — Cancer is present in pelvic lymph nodes (regardless of tumor size).
- Stage IIIC2 — Cancer is present in para-aortic lymph nodes (regardless of tumor size).
Stage IV — Cancer has spread to nearby organs or distant sites.
- Stage IVA — Cancer invades the lining of the bladder or rectum.
- Stage IVB — Cancer has spread to distant organs such as the lungs, liver, or bones.

What is the prognosis?

HPV-associated adenocarcinoma generally has a more favorable outlook than HPV-independent cervical adenocarcinomas, especially when it is found at an early stage. Stage is the single most important prognostic factor, with five-year survival rates that decline as the stage increases:

Stage I — Five-year survival is generally in the range of 85 to 95%.
Stage II — Five-year survival is generally in the range of 65 to 75%.
Stage III — Five-year survival is generally in the range of 40 to 50%.
Stage IV — Five-year survival is lower, generally in the range of 15 to 20%, depending on the extent and location of distant spread.

Within each stage, several additional features from the pathology report influence the chance of recurrence:

Silva pattern — Pattern A is associated with a very low risk of lymph node spread and recurrence. Pattern B and Pattern C carry progressively higher risk.
Lymphovascular invasion — Increases the risk of lymph node spread and recurrence at any stage.
Lymph node status — The presence and number of involved lymph nodes, and whether the involved nodes are pelvic or para-aortic, all influence prognosis.
Surgical margin status — Negative margins are associated with a lower risk of local recurrence. Positive margins increase the chance that residual disease is present.
Tumor size and depth of invasion — Larger and deeper tumors are associated with a higher risk of recurrence and worse outcomes.
Perineural invasion — When present, is associated with a higher risk of local recurrence.

What happens after this diagnosis?

Once invasive HPV-associated adenocarcinoma is diagnosed, the gynecologic oncology team will discuss the treatment options with the patient. The choice depends on the stage, the size and Silva pattern of the tumor, the patient’s age and wish to preserve fertility, overall health, and other findings on the pathology report.

Options that the team may consider include:

Cone biopsy or simple hysterectomy — For the earliest invasive cancers (typically stage IA1) without high-risk features, complete excision with a cone biopsy may be sufficient, especially for patients who wish to preserve fertility. Simple hysterectomy (removal of the uterus and cervix without removal of surrounding tissue) is another option for patients who have completed their families.
Radical hysterectomy with pelvic lymph node assessment — For patients with stage IA2 to stage IIA cancer, radical hysterectomy (removal of the uterus, cervix, parametrium, and upper vagina) combined with sentinel lymph node biopsy or pelvic lymph node dissection is a commonly considered approach. The pathology report from this specimen provides definitive staging and the information needed to decide whether additional treatment is needed.
Fertility-sparing radical trachelectomy — For carefully selected patients with small early-stage tumors who wish to preserve the ability to become pregnant, removal of the cervix while leaving the uterus in place may be discussed.
Chemoradiation therapy — For locally advanced cancer (typically stage IB3 and higher), the team often discusses concurrent chemotherapy and radiation rather than primary surgery. Chemoradiation may also be added after surgery when the pathology report shows high-risk features such as positive margins, parametrial invasion, or lymph node involvement.
Systemic therapy for advanced or recurrent disease — For stage IVB or recurrent disease, the medical oncology team discusses systemic options including chemotherapy and immune checkpoint inhibitor therapy. Eligibility for immunotherapy (pembrolizumab) depends on the PD-L1 result, with a CPS of 1 or higher generally required.

After treatment, regular follow-up is essential. Surveillance typically includes physical and pelvic examinations every three to six months for the first two years, then less frequently. Imaging and additional tests may be added based on the original stage and pathology findings. Your gynecologic oncology team will tailor the follow-up plan to your specific situation.

Questions to ask your doctor

What is the stage of my cervical cancer using both the TNM and FIGO systems?
How large is the tumor, and how deeply has it grown into the cervix?
Was a Silva pattern reported, and what does it mean for my prognosis and treatment options?
Was lymphovascular invasion present in my pathology specimen?
Was perineural invasion present?
Were the surgical margins negative, close, or positive?
How many lymph nodes were examined, and were any involved by cancer?
Was p16 testing performed, and what did the result show?
Was PD-L1 testing performed, and what does the result mean for my treatment options?
What treatment options would you discuss with me based on my pathology findings?
I want to preserve my fertility — what options are available to me given my pathology results?
What is my expected prognosis based on the findings in my pathology report?
What will my follow-up schedule look like after treatment?
What symptoms should prompt me to contact you between scheduled appointments?