HPV-Associated Squamous Cell Carcinoma of the Nasal Cavity and Paranasal Sinuses: Understanding Your Pathology Report

By Jason Wasserman MD PhD FRCPC
July 9, 2026

HPV-associated squamous cell carcinoma is a type of cancer that starts from squamous cells, the flat cells that line the inside of the nasal cavity and the paranasal sinuses. The nasal cavity is the hollow space inside the nose that warms, moistens, and filters the air we breathe. The paranasal sinuses are air-filled spaces in the bones around the nose that help produce mucus and lighten the weight of the skull. This cancer is linked to infection with high-risk types of human papillomavirus (HPV), and it is considered a distinct type of squamous cell carcinoma because it behaves differently from tumors not related to HPV. 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 squamous cell carcinoma?

HPV-associated squamous cell carcinoma of the nasal cavity and paranasal sinuses 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. In most people, the immune system clears the virus, but when the infection persists, the virus interferes with the normal controls that keep squamous cells from growing out of control, which can lead to cancer over time. Other factors, such as smoking or exposure to certain workplace chemicals, may add to a person’s overall cancer risk, but HPV plays the central role in this specific tumor type.

What are the symptoms?

The symptoms of HPV-associated squamous cell carcinoma of the nasal cavity and paranasal sinuses depend on the tumor’s size and location. Early tumors may cause mild or vague symptoms, while larger tumors can produce more noticeable problems. Common symptoms include nasal blockage or congestion, nosebleeds, facial pain or pressure, swelling in or around the nose, difficulty breathing through one nostril, and a reduced sense of smell. Some tumors cause few symptoms at first and are only discovered once they grow larger or extend into nearby structures.

How is the diagnosis made?

The diagnosis of HPV-associated squamous cell carcinoma of the nasal cavity and paranasal sinuses 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 tissue is removed from the tumor, typically via an endoscope through the nose. In some cases the diagnosis is made after the tumor has been surgically removed, especially if a biopsy was not performed first or did not provide enough tissue.

Under the microscope, HPV-associated squamous cell carcinoma is usually made up of nests, lobules, or ribbon-like groups of tumor cells. These groups often grow in a smooth, pushing pattern into the surrounding tissue rather than breaking through it irregularly, and the surrounding tissue often shows little reaction even when the tumor grows deeply or destroys bone. Some tumors grow in a papillary pattern, forming finger-like projections along the surface lining. The tumor cells typically have large nuclei and relatively little cytoplasm, so the nucleus occupies most of the cell, and cells at the edges of the nests are often aligned in an orderly row. Most tumors show the classic nonkeratinizing appearance (they do not produce keratin, a tough protein found in skin and hair), although some show keratinizing, basaloid (small, dark cells), or mixed (adenosquamous) features. Areas of cell death (necrosis) may be present, and the degree of abnormality can vary from case to case.

Because this tumor is defined by its link to HPV, testing for the virus is a key part of the diagnosis. Immunohistochemistry, a test that uses specially labeled antibodies to detect proteins in tumor cells, is used to look for p16, a protein that accumulates when high-risk HPV disrupts normal cell control. Strong, widespread p16 staining strongly supports HPV involvement. To confirm the virus directly, in situ hybridization may be performed to detect high-risk HPV within the tumor cells. Once the diagnosis is confirmed, imaging studies such as CT and MRI are used to show where the tumor is and how far it has spread. CT is best for showing bone damage, while MRI gives better detail of soft tissues, including spread into muscles, nerves, or the eye.

Histologic grade

Unlike many other cancers, HPV-associated squamous cell carcinoma of the nasal cavity and paranasal sinuses is not assigned a histologic grade based on how abnormal the cells look. The diagnosis is defined by the tumor’s link to HPV and its growth pattern rather than by a grade, so your pathology report will usually not include a grade number for this tumor, and this is expected. The pathologist’s assessment focuses instead on the extent of the tumor, features such as perineural and lymphovascular invasion, and the results of HPV testing.

Perineural invasion

In HPV-associated squamous cell carcinoma of the nasal cavity and paranasal sinuses, the pathologist looks for perineural invasion, which means 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 pain and sensation between the body and the brain. Perineural invasion matters because cancer cells can use nerves as a pathway to travel into nearby tissues, which raises the risk of the tumor returning after treatment. If perineural invasion is present, it will be described in your pathology report.

Lymphovascular invasion

Lymphovascular invasion means that cancer cells from the HPV-associated squamous cell carcinoma were seen 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 lungs. 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. Because tumors in the nasal cavity and sinuses are often removed in more than one piece rather than as a single intact specimen, it can be difficult or impossible to reliably determine whether all margins are clear. In such cases, the report may state that the margins cannot be fully assessed or are indeterminate.

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. Cancer cells from an HPV-associated squamous cell carcinoma of the nasal cavity and paranasal sinuses can travel through lymphatic vessels to reach these nodes. When lymph nodes are removed during surgery, 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. 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 evidence of cancer cells spreading to other parts of the body (metastasis), may influence decisions about additional treatment, such as radiation therapy, chemotherapy, or immunotherapy.

Biomarker and molecular testing

For HPV-associated squamous cell carcinoma of the nasal cavity and paranasal sinuses, the HPV and p16 tests used to confirm the diagnosis are described above under “How is the diagnosis made?” The biomarker below becomes relevant when the cancer is advanced, has come back after treatment, or has spread to distant sites.

PD-L1

PD-L1 (programmed death-ligand 1) is a protein that some cancer cells display on their surface to avoid being attacked by the immune system. Drugs called immune checkpoint inhibitors block this protein, allowing the immune system to recognize and attack the cancer. In squamous cell carcinomas of the head and neck, PD-L1 testing helps identify patients who may benefit from these drugs when the cancer is recurrent or metastatic.

PD-L1 is measured by immunohistochemistry and, for head and neck cancers, is usually reported as a Combined Positive Score (CPS), which reflects PD-L1 staining on both the cancer cells and nearby immune cells. A higher score indicates a greater chance that immunotherapy will be effective. Your report will state the score and whether it is above or below the threshold used for treatment decisions. A CPS of 1 or higher is generally used to identify patients who may be eligible for the immune checkpoint inhibitor pembrolizumab (Keytruda) in recurrent or metastatic disease. A result below the threshold does not rule out immunotherapy in every situation, but it makes eligibility less likely. Evidence on PD-L1 specifically in HPV-associated squamous cell carcinoma of the nasal cavity and paranasal sinuses is still developing, and your medical oncology team will explain how the result applies to your situation. You can read more in the PD-L1 testing overview and in the full Biomarkers and Molecular Testing section.

Pathologic stage (pTNM)

The pathologic stage for HPV-associated squamous cell carcinoma of the nasal cavity and paranasal sinuses 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. For HPV-associated squamous cell carcinoma of the nasal cavity and paranasal sinuses, the outlook depends mainly on the size and location of the tumor, how far it has spread, and the person’s overall health. The five-year survival rate for sinonasal squamous cell carcinoma overall is approximately 60 percent. Several findings on the pathology report are associated with a higher risk of the cancer returning after treatment.

Tumor stage — Tumors that have grown into the orbit, skull base, or brain are harder to remove completely and carry a higher risk of recurrence.
Lymph node involvement — Cancer found in the lymph nodes, and especially extranodal extension, is associated with a higher risk of spread.
Perineural and lymphovascular invasion — Either finding is associated with a higher chance that the tumor will return.
Margin status — Positive or close margins are associated with a higher risk of the cancer coming back in the same area.
HPV status — Some studies suggest HPV-associated tumors may have a better outlook than tumors not linked to HPV, though outcomes still vary from person to person, and this benefit is less consistent in the nasal cavity and sinuses than it is in the oropharynx.

What happens after the diagnosis?

Treatment for HPV-associated squamous cell carcinoma of the nasal cavity and paranasal sinuses 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 stage of the tumor, along with the specific findings in the pathology report.

Surgery is the main treatment for tumors that can be removed, and may be performed endoscopically through the nose or through a larger open approach for more extensive tumors. The goal is complete removal of the tumor with clear margins. When the report shows positive or close margins, perineural invasion, lymphovascular invasion, or cancer in the lymph nodes, radiation therapy after surgery may be considered, and these specific findings directly inform that decision. For advanced disease, chemotherapy may be added, and for recurrent or metastatic tumors, immunotherapy may be an option depending on the PD-L1 result. After treatment, regular follow-up with imaging and physical examination is used to watch for any sign of the cancer returning.

Questions to ask your doctor

Where exactly did my cancer start — the nasal cavity, maxillary sinus, or ethmoid sinus?
Was my tumor confirmed to be HPV-associated, and how was that determined?
What is my pathologic stage (pT and pN), and what does that mean for my treatment?
Were the surgical margins negative, or were they indeterminate because the tumor was removed in pieces?
Was perineural invasion present in my tumor?
Was lymphovascular invasion present in my tumor?
Were lymph nodes examined, and did any contain cancer cells? Was extranodal extension present?
Was PD-L1 testing performed, and if so, what was the result?
Will I need radiation therapy, chemotherapy, or immunotherapy, and which findings in my report influenced that recommendation?
What signs of recurrence should I watch for, and how will I be monitored after treatment?
Are there any clinical trials available for my type of cancer?