HPV-Related Multiphenotypic Sinonasal Carcinoma: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC
July 9, 2026

HPV-related multiphenotypic sinonasal carcinoma is a rare type of cancer that develops in the nasal cavity or the paranasal sinuses, the air-filled spaces in the bones around the nose. It is linked to infection with high-risk human papillomavirus (HPV). The tumor is called “multiphenotypic” because it consists of more than one cell type, including cells resembling those typically found in salivary gland tumors. An important and reassuring feature of this cancer is that, although it can look worrisome under the microscope, it usually grows slowly and rarely spreads to other parts of the body. 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-related multiphenotypic sinonasal carcinoma?

HPV-related multiphenotypic sinonasal carcinoma is caused by infection with high-risk HPV. High-risk HPV is a common virus that can infect the cells lining the nose and sinuses. When the infection persists, the virus interferes with the normal controls that keep cells from growing out of control, which can lead to a tumor over time. Unlike many other HPV-related cancers, which are most often linked to HPV type 16, this tumor is characteristically associated with a less common high-risk type, HPV type 33. Environmental irritants may add to a person’s overall risk, but HPV is the central and defining cause of this tumor.

What are the symptoms?

The symptoms of HPV-related multiphenotypic sinonasal carcinoma depend on the size and location of the tumor. Common symptoms include nasal congestion or a blocked nose, nosebleeds, facial pain or pressure, a decreased sense of smell, swelling in the face or around the nose, and frequent sinus infections that do not improve with treatment. Because these symptoms overlap with common, noncancerous conditions such as sinus infections, the diagnosis often requires a biopsy and additional testing before it is made.

How is the diagnosis made?

The diagnosis of HPV-related multiphenotypic sinonasal carcinoma is made after a tissue sample is examined under the microscope by a pathologist. The sample is usually obtained through a biopsy, in which a small piece of the tumor is removed, typically via an endoscope through the nose. In some cases, the diagnosis is made after the tumor has been surgically removed.

Under the microscope, HPV-related multiphenotypic sinonasal carcinoma is usually composed of groups of small, round, or oval cells arranged in solid sheets or circular clusters. A defining feature is that the tumor contains a mix of cell types. Some areas contain two salivary gland-type cells: ductal cells, which form small tube-like structures, and myoepithelial cells, which normally surround and support the ductal cells. Because of this appearance, the tumor can closely resemble a salivary gland cancer called adenoid cystic carcinoma. Other areas may contain cells that look like squamous cell carcinoma, a different type of cancer that produces keratin (a tough protein found in skin and nails), or cells that appear elongated or clear. The tumor often has many mitotic figures (cells caught in the act of dividing), and areas of cell death (necrosis) may be present. The tumor commonly invades nearby bone, but it usually does not invade nerves or blood vessels, which is one reason it tends to grow slowly.

Because this tumor can resemble several other cancers, additional tests are needed to confirm the diagnosis. Immunohistochemistry, a test that uses specifically labeled antibodies to detect proteins in tumor cells, is used to demonstrate that both salivary gland-type cell populations are present. Myoepithelial cells typically stain for p40, p63, smooth muscle actin (SMA), and calponin, while ductal cells typically stain for KIT (CD117). Markers such as S100 and SOX10 are expressed in both cell types. The tumor cells also stain strongly and uniformly for p16, a protein that builds up when high-risk HPV disrupts normal cell control.

An important point specific to this tumor is that p16 staining alone is not enough to confirm HPV infection here, because p16 can be positive for reasons unrelated to the virus. For this reason, the diagnosis is confirmed with in situ hybridization that detects high-risk HPV directly within the tumor cells. Once the diagnosis is confirmed, imaging studies such as CT and MRI are used to determine the size of the tumor and whether it has grown into nearby structures.

Histologic grade

HPV-related multiphenotypic sinonasal carcinoma is not assigned a histologic grade based on how abnormal the cells look. This is an important point, because the tumor can appear worrisome under the microscope, with many dividing cells and areas of cell death, features that in other cancers would suggest a fast-growing tumor. Despite this appearance, HPV-related multiphenotypic sinonasal carcinoma usually behaves in a slow-growing way and rarely spreads. For this reason, your pathology report will not include a grade number, and this is expected and appropriate for this diagnosis.

Perineural invasion

Perineural invasion means that cancer cells were seen attached to or growing along the outside of a nerve. Nerves run throughout the head and neck, carrying signals such as temperature, pressure, and pain between the body and the brain. In most other cancers, perineural invasion increases the risk of tumor recurrence after treatment. In HPV-related multiphenotypic sinonasal carcinoma, perineural invasion is typically absent, and this is one of the features that helps explain why this tumor tends to behave in a slow-growing way. If perineural invasion is present, it will be described in your pathology report.

Lymphovascular invasion

Lymphovascular invasion means that cancer cells were found within a blood or lymphatic vessel. Blood vessels carry blood throughout the body, and lymphatic vessels carry a fluid called lymph. Both types of vessels connect to other parts of the body, so cancer cells that enter them can travel to distant sites such as lymph nodes or the liver. As with perineural invasion, lymphovascular invasion is typically absent in HPV-related multiphenotypic sinonasal carcinoma, consistent with how rarely this tumor spreads. If lymphovascular invasion is present, it will be included in your pathology report.

Surgical margins

A surgical margin is the edge of the tissue that the surgeon cuts through when removing the tumor. Margins are assessed after a procedure that removes the entire tumor, such as an excision or resection, and are usually not evaluated after a biopsy, which removes only part of the tumor. Margin status is especially important in HPV-related multiphenotypic sinonasal carcinoma, because the most common problem after treatment is the tumor growing back in the same area, and a complete removal lowers that risk.

Negative margin — No cancer cells are present at the cut edge of the tissue. This suggests the tumor was completely removed.
Close margin — Cancer cells are near the cut edge but do not reach it. The distance from the nearest cancer cells to the edge may be measured and reported, because a very close margin can be relevant to decisions about additional treatment.
Positive margin — Cancer cells are present at the cut edge. This means some tumor may remain in the body, and the treatment team will use this finding when considering whether additional surgery or radiation therapy is appropriate.

Lymph nodes

Lymph nodes are small immune organs found throughout the head and neck. In many cancers, cancer cells can travel through lymphatic vessels to reach these nodes. HPV-related multiphenotypic sinonasal carcinoma only rarely spreads to lymph nodes, so lymph nodes are usually removed only if they are enlarged or look suspicious on imaging. When lymph nodes are removed, they are examined under the microscope and the results are described in your pathology report.

Your report will include the total number of lymph nodes examined, the number that contain cancer cells, and the size of the largest deposit of cancer cells (often called a “focus” or “deposit”). A node that contains cancer cells is described as “positive,” and a node with no cancer cells is described as “negative.” The pathologist also checks for extranodal extension, which means cancer cells have broken through the outer capsule of a lymph node and spread into the surrounding tissue. Lymph node findings are used to determine the pathologic nodal stage (pN) and, along with the finding of cancer cells spreading to other parts of the body (metastasis), may influence decisions about additional treatment.

Pathologic stage (pTNM)

The pathologic stage for HPV-related multiphenotypic sinonasal carcinoma is based on the TNM staging system, as defined in the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 8th edition. This system describes the tumor using three categories: the primary tumor (pT), the regional lymph nodes (pN), and distant spread (pM). In general, a higher stage reflects more advanced disease. The metastatic stage (pM) is determined by imaging and clinical evaluation, not by the pathologist examining the surgical specimen. Because the tumor stage depends on where the cancer began, the criteria differ for tumors that start in the maxillary sinus versus those that start in the nasal cavity or ethmoid sinus.

Tumor stage (pT) — maxillary sinus

Tis — The cancer is “in situ,” confined to the surface lining and has not invaded deeper tissue.
pT1 — The tumor is limited to the lining (mucosa) of the maxillary sinus and has not damaged the surrounding bone.
pT2 — The tumor has eroded or destroyed bone, possibly including the hard palate or the middle nasal passage, but has not reached the back wall of the maxillary sinus or the pterygoid plates (wing-shaped bones at the base of the skull).
pT3 — The tumor has invaded the back wall of the maxillary sinus, the tissue beneath the skin, the floor or inner wall of the orbit (the socket that holds the eye), the pterygoid fossa (a depression at the side of the skull), or the ethmoid sinuses.
pT4a — The tumor has grown into the front part of the eye socket, the skin of the cheek, the cribriform plate (a bony shelf at the top of the nasal cavity), or the sphenoid or frontal sinuses.
pT4b — The tumor has grown into the deepest part of the eye socket, the coverings of the brain, the brain itself, the middle cranial fossa, specific cranial nerves, the upper throat behind the nose (nasopharynx), or a bony area at the base of the skull (clivus).

Tumor stage (pT) — nasal cavity and ethmoid sinus

Tis — The cancer is “in situ,” confined to the surface lining.
pT1 — The tumor is limited to one area (subsite) of the nasal cavity or ethmoid sinus, with or without involvement of the surrounding bone.
pT2 — The tumor involves two subsites within the nasal cavity or ethmoid sinus, or extends into an adjacent area within this region, with or without involvement of the surrounding bone.
pT3 — The tumor has invaded the floor or inner wall of the orbit, the maxillary sinus, the palate (the roof of the mouth), or the cribriform plate.
pT4a — The tumor has grown into the front part of the eye socket, the skin of the nose or cheek, a limited area at the base of the skull, or nearby bones.
pT4b — The tumor has grown into the deepest part of the eye socket, the coverings of the brain, the brain itself, the middle cranial fossa, specific cranial nerves, or deep areas of the skull.

Nodal stage (pN)

pNX — The lymph nodes could not be assessed.
pN0 — No cancer cells were found in any of the lymph nodes examined.
pN1 — Cancer cells were found in a single lymph node on the same side of the neck as the tumor. The node is 3 cm or smaller and shows no extranodal extension.
pN2a — Cancer cells were found in a single lymph node on the same side of the neck that is either 3 cm or smaller with extranodal extension, or larger than 3 cm but no larger than 6 cm without extranodal extension.
pN2b — Cancer cells were found in more than one lymph node on the same side of the neck. None is larger than 6 cm, and none shows extranodal extension.
pN2c — Cancer cells were found in lymph nodes on both sides of the neck, or on the opposite side from the tumor. None is larger than 6 cm, and none shows extranodal extension.
pN3a — A lymph node containing cancer cells is larger than 6 cm and shows no extranodal extension.
pN3b — A lymph node with extranodal extension is present, or multiple involved nodes show extranodal extension.

What is the prognosis?

Prognosis refers to the likely long-term outcome after a diagnosis. The outlook for HPV-related multiphenotypic sinonasal carcinoma is generally favorable. Even though the tumor can look worrisome under the microscope, it tends to grow slowly and is much less like other high-grade carcinomas. The most common problem after treatment is the tumor growing back in the same area (local recurrence), which happens in about one-third of cases and can sometimes occur years later. Spread to distant parts of the body is very rare, occurring in only about 5 percent of cases, and spread to lymph nodes or death from the tumor is uncommon. With complete surgical removal and careful long-term monitoring, most patients do well.

A few findings in the pathology report can affect the risk of the tumor returning.

Margin status — A positive or close margin is associated with a higher risk of the tumor growing back in the same area.
Tumor extent — Tumors that have grown into the orbit, skull base, or other nearby structures can be harder to remove completely.

What happens after the diagnosis?

Treatment for HPV-related multiphenotypic sinonasal carcinoma is planned by a multidisciplinary team that may include ear, nose, and throat (ENT) surgeons, neurosurgeons for tumors near the skull base, radiation oncologists, and medical oncologists. The approach is guided by the location, size, and extent of the tumor, as well as the specific findings in the pathology report.

Surgery is the main treatment, with the goal of completely removing the tumor with clear margins. When the report shows positive or close margins, radiation therapy after surgery may be considered to lower the chance of the tumor returning in the same area. Because this tumor rarely spreads, chemotherapy is usually not needed. After treatment, long-term follow-up with imaging and physical examination is important, since the tumor can come back in the same area years later. Regular monitoring allows any recurrence to be found and treated early.

Questions to ask your doctor

Where exactly did my cancer start — the nasal cavity, maxillary sinus, or ethmoid sinus?
Was the diagnosis confirmed with HPV testing, such as HPV in situ hybridization, and not p16 alone?
What is my pathologic stage (pT and pN), and what does that mean for my treatment?
Were the surgical margins negative, and does the report suggest the tumor was completely removed?
Was perineural or lymphovascular invasion present in my tumor?
Given that this tumor rarely spreads, what is my personal risk of it coming back?
Will I need radiation therapy after surgery, and which findings in my report influenced that recommendation?
How often will I need imaging and follow-up visits, and for how long?
What signs of recurrence should I watch for between visits?
Are there any clinical trials available for my type of cancer?