HPV Independent Gastric-Type Adenocarcinoma of the Cervix: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC
March 13, 2026

HPV-independent gastric-type adenocarcinoma is a rare type of cervical cancer that develops from glandular cells in the cervix. Glandular cells normally produce mucus and line the cervical canal.

This cancer is called HPV-independent because it develops without infection by human papillomavirus (HPV). Instead, the tumor cells show features resembling those of cells found in the stomach, particularly the glands that produce mucus in the lower part of the stomach (the pylorus).

Gastric-type adenocarcinoma accounts for about 10–15% of cervical adenocarcinomas worldwide and may occur more commonly in some regions. Compared with HPV-associated cervical adenocarcinoma, this tumor usually occurs in older patients, typically in their 50s.

What are the symptoms of HPV-independent gastric-type adenocarcinoma?

Patients with HPV independent gastric type adenocarcinoma of the cervix may develop symptoms related to the tumor or may seek medical attention because of abnormal vaginal discharge.

The most common symptoms include abnormal vaginal bleeding and watery vaginal discharge. Some patients may also experience pelvic pain or notice a mass in the cervix.

Because this tumor often develops deeper within the cervix, it may not always be detected early through routine cervical screening.

What causes HPV-independent gastric-type adenocarcinoma?

The exact cause of gastric-type adenocarcinoma of the cervix is not fully understood. Unlike most cervical cancers, this tumor is not caused by HPV infection. Instead, it appears to develop through other molecular changes in cervical glandular cells.

Some cases occur in patients with Peutz–Jeghers syndrome, a hereditary condition caused by mutations in the STK11 gene. These mutations can increase the risk of several types of tumors, including gastric-type adenocarcinoma of the cervix.

How is this diagnosis made?

The diagnosis of HPV-independent gastric-type adenocarcinoma usually begins when symptoms lead to an examination of the cervix or when abnormal findings are seen during imaging or a pelvic exam.

Tissue from the cervix is removed through procedures such as a biopsy, endocervical curettage, or cone biopsy. A pathologist examines the tissue under the microscope to determine the type of cancer.

If surgery is performed, the pathologist also examines the removed tissue to determine the size of the tumor, how deeply it has grown into the cervix, and whether it has spread to nearby structures.

Microscopic features

Under the microscope, gastric-type adenocarcinoma is composed of glands lined by cells that produce large amounts of mucus.

The tumor cells often have clear or pale pink cytoplasm and distinct cell borders. The nuclei may be enlarged and irregular, and visible nucleoli may be present.

Some tumors are well-differentiated and form glands that appear relatively normal but grow in an irregular, haphazard pattern deep within the cervix. In other cases, the tumor forms irregular glands, clusters of cells, or single cells with more obvious cellular abnormalities.

Many tumors show destructive invasion into the surrounding cervical tissue, and lymphovascular invasion is common.

Immunohistochemistry

Immunohistochemistry (IHC) is a laboratory test that uses antibodies to detect specific proteins inside tumor cells.

Gastric-type adenocarcinomas often show staining for CK7, CEA, and PAX8, which support a cervical origin of the tumor.

Markers associated with gastric differentiation, such as MUC6 or HIK1083, may also be positive. These markers reflect the similarity between the tumor cells and gastric-type mucus-producing cells.

Hormone receptors such as estrogen receptor (ER) and progesterone receptor (PR) are usually negative.

Staining for p16 is typically negative or only patchy, which helps distinguish this tumor from HPV-associated adenocarcinoma, where p16 staining is usually strong and diffuse.

In situ hybridization

In situ hybridization (ISH) is a laboratory test that detects HPV DNA or RNA directly within tumor cells.

This test uses specialized probes that bind to HPV genetic material. If HPV DNA or RNA is present, the probes produce a visible signal under the microscope.

HPV-independent gastric-type adenocarcinoma does not show HPV signals on in situ hybridization testing, confirming that the tumor developed without HPV infection.

Biomarkers

Biomarker testing examines proteins or genetic features in tumor cells that may help guide treatment decisions. These tests are usually performed on tumor tissue using immunohistochemistry or molecular methods. Not all biomarkers are tested in every case, but the results can provide important information about treatment options.

PD-L1

PD-L1 is a protein that helps cancer cells evade immune system detection.

Testing for PD-L1 is performed using immunohistochemistry and is often reported using a combined positive score (CPS). This score measures PD-L1 expression in tumor cells and nearby immune cells.

Tumors that express PD-L1 may respond to immune checkpoint inhibitor therapy, which is sometimes used to treat advanced or recurrent cervical cancer.

Other features to look for in your pathology report

Tumor size and depth of invasion

Once the diagnosis is made, the pathologist measures the tumor to determine its size and how deeply it has grown into the cervix.

Tumor size describes how far the cancer extends along the cervix. Depth of invasion describes how far the tumor has grown from the surface into the supporting tissue of the cervix.

These measurements are important because tumors that invade more deeply are more likely to spread to lymph nodes or nearby organs.

Tumor spread

Pathologists examine the tumor to determine whether it has spread beyond the cervix.

The tumor may extend into nearby structures such as the vagina, uterus, parametrium, pelvic wall, bladder, or rectum. The parametrium is the fibrous tissue that surrounds the cervix.

Gastric-type adenocarcinoma often shows destructive invasion and early spread beyond the cervix, which contributes to its more aggressive behavior.

Lymphovascular invasion

Lymphovascular invasion (LVI) means tumor cells are present inside small lymphatic channels or blood vessels in the cervix.

These vessels normally carry fluid or blood through the body. When tumor cells enter these channels, they may travel to nearby lymph nodes or other organs. Lymphovascular invasion is relatively common in gastric-type adenocarcinoma and increases the risk of cancer spread.

Perineural invasion

Perineural invasion (PNI) means that tumor cells are growing along or around nerves in the cervix.

This pattern may increase the risk of the cancer returning in nearby tissues and may influence treatment decisions.

Margins

Margins are the edges of the tissue removed during surgery.

A negative margin means that no cancer cells are present at the edge of the tissue, suggesting that the tumor was completely removed. A positive margin means that cancer cells extend to the edge, which increases the risk that some tumor cells remain.

Margins are evaluated in cone biopsies and hysterectomy specimens.

Lymph nodes

Lymph nodes are small immune organs that help filter harmful substances from the body.

The cervix drains into lymph nodes in the pelvis and abdomen. During surgery for cervical cancer, lymph nodes from these areas may be removed and examined under the microscope.

If tumor cells are found in these lymph nodes, the cancer is considered to have spread beyond the cervix, and the stage of the cancer increases.

When tumor cells are present in lymph nodes, the pathology report may describe the size of the tumor deposits.

  • Isolated tumor cells measure 0.2 mm or less.
  • Micrometastases measure more than 0.2 mm but 2 mm or less.
  • Macrometastases measure more than 2 mm.

The pathology report may also describe the number of lymph nodes examined, the number containing tumor cells, and the location of involved nodes.

How is HPV associated cervical cancer staged?

Staging describes how far the cancer has spread within the cervix and beyond. It is the most important factor for predicting outcome and deciding on treatment. Two systems are commonly used for cervical cancer: TNM and FIGO.

  • The TNM system records tumor size and spread in the cervix (T), whether lymph nodes contain cancer (N), and whether the cancer has spread to distant organs (M).

  • The FIGO system focuses on how far the cancer has spread beyond the cervix into surrounding tissues, lymph nodes, or distant sites. Gynecologic oncologists widely use it to guide treatment planning.

TNM pathologic stage

  • The letter T describes how far the tumor has grown in and around the cervix.

    • T1a means the tumor is only visible under the microscope and measures no more than 5 millimeters in depth and 7 millimeters in width.

    • T1b means that the tumor is visible or measures deeper than five millimeters or wider than seven millimeters.

    • T2a means that the tumor has spread beyond the cervix and uterus but has not entered the parametrium.

    • T2b means that the tumor has grown into the parametrium.

    • T3a means that the tumor involves the lower part of the vagina.

    • T3b means that the tumor reaches the pelvic wall or blocks a ureter, which can harm the kidneys.

    • T4 means that the tumor has grown into the bladder or rectum or has extended beyond the pelvis.

  • The letter N describes lymph nodes.

    • NX means that no nodes were removed.

    • N0 means that no cancer was found in the nodes.

    • N0 with isolated tumor cells means that only tiny clusters smaller than zero point two millimeters were present.

    • N1 means that a larger cancer deposit was found in at least one node.

  • The letter M describes distant spread to organs such as the lungs or liver.

FIGO stage

  • Stage I means that the cancer is confined to the cervix.

    • Stage IA1 means that the depth of invasion is three millimeters or less.

    • Stage IA2 means the depth of invasion is between 3 and 5 millimeters.

    • Stage IB1 means that the tumor is two centimetres or smaller.

    • Stage IB2 means the tumor is more than 2 centimetres but no more than 4 centimetres.

    • Stage IB3 means that the tumor is larger than four centimetres.

  • Stage II means that the cancer has spread beyond the cervix but not to the pelvic wall or the lower third of the vagina.

    • Stage IIA1 means that the tumor involves the upper vagina and measures four centimetres or less.

    • Stage IIA2 means that the tumor in the upper vagina is larger than four centimetres.

    • Stage IIB means that the tumor extends into the parametrium.

  • Stage III means more extensive local spread.

    • Stage IIIA means that the cancer involves the lower third of the vagina.

    • Stage IIIB means that the cancer reaches the pelvic wall or blocks a ureter.

    • Stage IIIC1 means that cancer is present in pelvic lymph nodes.

    • Stage IIIC2 means that cancer is present in para-aortic lymph nodes.

  • Stage IV means spread to nearby organs or to distant sites.

    • Stage IVA means invasion of the bladder or rectum.

    • Stage IVB means distant metastasis to organs such as the lungs, liver, or bones.

Staging guides treatment and helps predict outcome.

Questions to ask your doctor

  • What stage is my cervical cancer?

  • How large is the tumor, and how deeply has it grown into the cervix?

  • Was lymphovascular invasion present?

  • Were the surgical margins clear?

  • Were lymph nodes involved?

  • Was PD-L1 testing performed, and what do the results mean for my treatment?

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