Squamous cell carcinoma (SCC) of the vulva is the most common type of vulvar cancer, making up more than 90% of vulvar cancers. It starts in the squamous cells that cover the surface of the vulva. Squamous cell carcinoma of the vulva develops along two main pathways. About one-third of cases are caused by infection with human papillomavirus (HPV), typically arising in younger patients from a precancerous condition called high grade squamous intraepithelial lesion (HSIL) of the vulva. The remaining two-thirds are HPV-independent and most often develop in older, postmenopausal patients in the setting of long-standing inflammatory skin conditions such as lichen sclerosus, frequently passing through a precancerous condition called differentiated vulvar intraepithelial neoplasia (dVIN).
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 squamous cell carcinoma of the vulva?
Squamous cell carcinoma of the vulva develops through two distinct pathways, with different risk factors and patient populations:
- HPV-associated pathway — About one-third of cases are caused by persistent infection with high-risk types of HPV, particularly HPV16. These tumors usually develop from HSIL of the vulva. HPV-associated vulvar cancers tend to occur in younger patients (often in their 40s to 60s) and may show specific microscopic patterns such as basaloid or warty growth.
- HPV-independent pathway — About two-thirds of cases are not caused by HPV. Most arise from long-standing chronic inflammatory skin conditions of the vulva, especially lichen sclerosus, and often pass through dVIN before becoming invasive. HPV-independent cancers tend to occur in older patients (often in their 60s to 80s) and usually have a keratinizing microscopic appearance.
Several factors increase the risk of developing squamous cell carcinoma of the vulva:
- Persistent high-risk HPV infection — The most important risk factor for the HPV-associated pathway. HPV16 is the most commonly involved type.
- Long-standing lichen sclerosus or lichen planus — Chronic inflammatory skin conditions that increase the risk along the HPV-independent pathway, especially when not well controlled with treatment.
- Cigarette smoking — Increases the risk for both pathways.
- A weakened immune system — Conditions such as HIV infection, organ transplantation, or long-term immunosuppressive therapy increase the risk.
- Previous precancerous lesions — A history of HSIL, dVIN, or treated cervical precancer.
- Older age — The risk of vulvar cancer increases with age, especially for the HPV-independent pathway.
What are the symptoms?
The symptoms of squamous cell carcinoma of the vulva depend on the size and location of the tumor. Common symptoms include:
- A lump, bump, or thickened area on the vulva — Often the first noticeable sign. It may feel firm, raised, or ulcerated.
- Persistent itching — Long-standing itching that does not improve with topical treatments is common, especially in the setting of underlying lichen sclerosus.
- Vulvar pain, burning, or tenderness — Discomfort that may be ongoing or worsen with sitting, walking, or sexual activity.
- An ulcer or sore that does not heal — A visible open area on the vulva that does not resolve over weeks to months should always be evaluated.
- Bleeding or unusual discharge — May appear as spotting on underwear or after intercourse.
- Changes in vulvar skin color or texture — White, red, or dark patches; new bumps; or areas of thickening.
- A lump in the groin — May indicate spread to lymph nodes.
Because some of these symptoms overlap with common, noncancerous skin conditions, vulvar cancer is sometimes diagnosed later than other gynecologic cancers. Any persistent vulvar symptom, especially in someone with lichen sclerosus or a previous precancerous lesion, deserves evaluation.
How is the diagnosis made?
The diagnosis of squamous cell carcinoma of the vulva is made when a sample of tissue from the vulva is examined under the microscope by a pathologist. The sample is typically obtained via a small biopsy of the area of concern during an office visit. After the diagnosis is confirmed, the entire tumor is usually removed by surgical excision, which provides a larger specimen for full evaluation. The pathology report for this larger specimen describes the tumor size and depth, the surgical margins, the presence of lymphovascular invasion or perineural invasion, and any lymph nodes examined.
To confirm the diagnosis and to determine which pathway the cancer developed through, the pathologist often performs additional tests called immunohistochemistry. The most commonly used tests in this setting are:
- p16 — Strong, continuous “block-type” p16 staining suggests an HPV-associated cancer. Negative or patchy p16 staining suggests an HPV-independent cancer.
- p53 — An abnormal p53 pattern (basal overexpression, complete loss of staining, or other aberrant patterns) is common in HPV-independent vulvar cancers, reflecting an underlying TP53 mutation.
- Squamous markers (p40, p63, cytokeratins) — These help confirm the squamous origin of the tumor, particularly for poorly differentiated tumors that may not look like obvious squamous cells under the microscope.
After diagnosis, imaging studies such as MRI, CT, or PET-CT are often performed to assess the size and local extent of the tumor and to look for spread to lymph nodes or distant organs.
Histologic grade
Histologic grade describes how closely the tumor cells resemble normal squamous cells under the microscope. Pathologists divide squamous cell carcinoma of the vulva into three grades:
- Well differentiated (grade 1) — The tumor cells look almost like normal squamous cells and often produce keratin. These tumors tend to grow more slowly.
- Moderately differentiated (grade 2) — The tumor cells clearly look different from normal squamous cells but can still be recognized as squamous in origin.
- Poorly differentiated (grade 3) — The tumor cells look very different from normal squamous cells and grow in a disorganized pattern. These cells can look so abnormal that immunohistochemistry may be needed to confirm the squamous origin. Poorly differentiated tumors tend to grow more quickly and are more likely to spread.
Grade is one factor considered alongside stage, tumor size, depth of invasion, and other features when planning treatment and estimating prognosis.
What does squamous cell carcinoma of the vulva look like under the microscope?
Under the microscope, squamous cell carcinoma of the vulva is composed of nests, sheets, and cords of abnormal squamous cells that have broken through the surface layer of the vulvar skin and grown into the underlying tissue, a process called invasion. The microscopic appearance varies depending on the pathway through which the cancer developed:
- Keratinizing pattern — The most common pattern, especially for HPV-independent cancers. The tumor cells produce keratin and often form round collections of keratin called keratin pearls. The cells are typically large with bright pink cytoplasm.
- Non-keratinizing pattern — The tumor cells do not produce as much keratin, and keratin pearls are uncommon.
- Basaloid pattern — More common in HPV-associated cancers. The tumor cells are small with dark nuclei and very little cytoplasm, resembling the basal cells of normal skin.
- Warty pattern — Also more common in HPV-associated cancers. The tumor has a cauliflower-like surface architecture, and tumor cells often show features of HPV infection such as koilocytes (cells with a clear halo around the nucleus).
- Verrucous pattern — A rare, distinctive growth pattern in which the tumor forms a thick, warty mass with bulbous downward extensions. Verrucous carcinoma is a slow-growing variant with a generally favorable prognosis.
Tumor size and depth of invasion
After surgery, the pathologist measures the tumor in three dimensions. The largest dimension is reported on the pathology report and is used to assign the tumor stage. Larger tumors are more likely to have spread to lymph nodes or nearby organs and carry a higher risk of recurrence.
Depth of invasion describes how far the tumor cells have grown from the surface layer of the vulvar skin into the underlying tissue. It is measured in millimeters. Tumors that invade more deeply are more likely to reach lymphatic channels and blood vessels and to spread to lymph nodes. Importantly, the method for measuring depth of invasion was updated in the 2021 FIGO revision and AJCC 9th edition. Depth is now measured from the basement membrane (the thin layer just below the surface skin) of the deepest adjacent tumor-free rete ridge to the deepest point of invasion. This newer method may yield slightly different numbers than older measurements, so reports issued before the 2021 revision should be interpreted with that in mind.
The combination of tumor size and depth of invasion determines whether the tumor is staged as pT1a (small and superficial) or pT1b (larger or more deeply invasive), as described in the staging section below.
Lymphovascular invasion
Lymphovascular invasion means that tumor cells are seen inside small lymphatic channels or blood vessels in or around the tumor. These vessels normally carry fluid or blood through the body. When tumor cells gain access to them, they can travel to nearby lymph nodes or distant organs. In squamous cell carcinoma of the vulva, lymphovascular invasion is associated with a higher risk of lymph node involvement and recurrence. Its presence often influences decisions about how extensively to evaluate the lymph nodes and whether to add radiation therapy after surgery.
Perineural invasion
Perineural invasion means that tumor cells are growing along or around small nerves in or around the tumor. This pattern of growth allows the cancer to extend along nerves beyond the visible tumor and is associated with a higher risk of local recurrence after treatment. Its presence may influence the team’s discussion about adding radiation therapy after surgery.
Surgical margins
A margin is the cut edge of tissue removed during surgery. The pathologist examines all of the margins under the microscope to determine whether any tumor cells are present at the cut edges of the specimen.
- Negative margin — No tumor cells are present at the cut edge of the tissue. Most reports will also state how far the closest tumor cells are from the margin, usually in millimeters.
- Positive margin — Tumor cells extend to the cut edge of the tissue. This means some tumor cells may still remain and increase the risk that the tumor will return in the same area.
The pathology report may also note whether HSIL or dVIN is present at the margins. Because these are precancerous conditions that can give rise to new invasive cancer over time, their presence at the margin is also important and may influence decisions about further surgery or surveillance.
Lymph nodes
Lymph nodes are small immune organs that filter fluid as it returns from the body’s tissues. The vulva drains first into lymph nodes in the groin (the inguinal and femoral lymph nodes), which are the first lymph nodes likely to contain tumor cells if the cancer has spread.
For early-stage tumors, a procedure called sentinel lymph node biopsy may be performed. This involves identifying and removing the first lymph node or two that drain the area of the tumor. If these sentinel nodes are negative, the rest of the lymph nodes can usually be left in place. For larger or higher-risk tumors, a more extensive lymph node dissection may be performed.
The pathology report describes the number of lymph nodes examined, the number that contain tumor cells, and the size of the largest 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 5 mm.
- Macrometastases — Tumor deposits larger than 5 mm.
The report may also describe whether tumor cells have broken through the outer wall of a lymph node into the surrounding tissue, a finding called extranodal extension, which is associated with a higher risk of recurrence.
Biomarker and molecular testing
Biomarker testing is most relevant in advanced, recurrent, or metastatic squamous cell carcinoma of the vulva, where the results help determine eligibility for specific systemic therapies. Not every biomarker is tested in every case.
PD-L1
PD-L1 is a protein that some tumor cells use to suppress the immune system’s ability to recognize and destroy them. Testing for PD-L1 is performed by immunohistochemistry on a tumor sample and is most commonly reported as the Combined Positive Score (CPS), which reflects PD-L1 expression on both tumor cells and nearby immune cells. 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 immune checkpoint inhibitor therapy is an appropriate option for advanced or recurrent disease.
Mismatch repair (MMR) testing
Mismatch repair proteins (MMR) are part of the cell’s system for correcting small errors that occur in DNA during cell division. When one or more of these proteins is absent from tumor cells, the result is called mismatch repair-deficient (dMMR), also known as microsatellite instability-high (MSI-high). MMR deficiency is uncommon in vulvar squamous cell carcinoma, but when present, it identifies patients who may benefit from pembrolizumab, which is approved across tumor types for cancers that are dMMR or MSI-high, regardless of where the cancer started.
Pathologic stage
Staging describes how far the cancer has spread. Stage is the most important factor in predicting outcome and in shaping the decisions made by the gynecologic and medical oncology teams about further treatment. Squamous cell carcinoma of the vulva is staged using two related systems: the AJCC pTNM system (currently AJCC 9th edition, effective January 1, 2024) and the FIGO system (currently the FIGO 2021 revision). The two systems are aligned, and FIGO is more commonly used by gynecologic oncologists for treatment planning.
The TNM system describes the size and extent of the tumor in the vulva (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 vulva or perineum.
- pT1a — Tumor 2 cm or less in greatest dimension with depth of invasion of 1 mm or less.
- pT1b — Tumor greater than 2 cm in greatest dimension, or with depth of invasion greater than 1 mm, still confined to the vulva or perineum.
- pT2 — Tumor of any size with extension to the lower one-third of the urethra, the lower one-third of the vagina, or the lower one-third of the anus.
- pT3 — Tumor of any size with extension to the upper two-thirds of the urethra, the upper two-thirds of the vagina, the bladder mucosa, or the rectal mucosa.
- pT4 — Tumor fixed to the pelvic bone.
Nodal stage (pN)
- pNX — Regional lymph nodes were not examined.
- pN0 — No cancer found in the regional lymph nodes.
- pN0(i+) — Only isolated tumor cells (clusters 0.2 mm or smaller) are present in regional lymph nodes.
- pN1 — 1 or 2 lymph node metastases, each smaller than 5 mm, without extranodal extension.
- pN1a — 1 lymph node metastasis less than 5 mm.
- pN1b — 2 lymph node metastases each less than 5 mm.
- pN2 — Larger lymph node deposits or extranodal extension.
- pN2a — 1 lymph node metastasis 5 mm or larger.
- pN2b — 2 or more lymph node metastases 5 mm or larger.
- pN2c — Lymph node metastasis with extranodal extension.
- pN3 — Fixed or ulcerated lymph node metastasis.
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 sites, including pelvic lymph nodes or distant organs such as the lungs, liver, or bones.
FIGO stage
The FIGO 2021 stage is reported alongside the TNM stage and is most commonly used for treatment planning:
- Stage I — Cancer confined to the vulva, no lymph node spread.
- Stage IA — Tumor 2 cm or less with depth of invasion 1 mm or less.
- Stage IB — Tumor greater than 2 cm or with depth of invasion greater than 1 mm.
- Stage II — Tumor of any size with extension to the lower one-third of the urethra, vagina, or anus, no lymph node spread.
- Stage III — Tumor with extension to the upper portions of perineal structures, or with lymph node spread (not fixed or ulcerated).
- Stage IIIA — 1 lymph node metastasis 5 mm or larger, or 1 to 2 lymph node metastases less than 5 mm.
- Stage IIIB — 2 or more lymph node metastases 5 mm or larger, or 3 or more lymph node metastases less than 5 mm.
- Stage IIIC — Lymph node metastasis with extranodal extension.
- Stage IV — More extensive local or distant spread.
- Stage IVA — Tumor fixed to the pelvic bone, extending to the upper urethra, upper vagina, bladder mucosa, or rectal mucosa; OR fixed or ulcerated lymph node metastasis.
- Stage IVB — Distant metastasis, including pelvic lymph nodes.
What is the prognosis?
The prognosis for squamous cell carcinoma of the vulva depends most strongly on the stage at diagnosis. Earlier stages have substantially better outcomes than advanced stages. Reported five-year overall survival rates by stage include approximately 85 to 90% for stage I, 70 to 80% for stage II, 50 to 60% for stage III, and approximately 15 to 20% for stage IV, although these numbers vary across studies and patient populations.
Several features in the pathology report influence the chance of recurrence:
- Stage at diagnosis — The single most important prognostic factor.
- Lymph node involvement — The strongest pathologic predictor of recurrence and survival. Negative groin lymph nodes are associated with the most favorable outcomes. Larger nodal deposits, multiple involved nodes, and extranodal extension are associated with a higher risk of recurrence.
- Surgical margin status — Negative margins are associated with a lower risk of local recurrence. Positive margins, or HSIL/dVIN at the margins, increase the risk of recurrence.
- Lymphovascular invasion — Increases the risk of lymph node spread and recurrence.
- Perineural invasion — Associated with a higher risk of local recurrence.
- Tumor size and depth of invasion — Larger and deeper tumors carry a higher risk of recurrence.
- Histologic grade — Poorly differentiated tumors tend to behave more aggressively.
- HPV status — Some studies suggest that HPV-associated vulvar cancers have a more favorable prognosis than HPV-independent cancers at the same stage, although stage and lymph node status remain the dominant factors.
What happens after this diagnosis?
Once squamous cell carcinoma of the vulva is diagnosed, the gynecologic oncology team will discuss treatment options with the patient. Decisions depend on the stage, the size and location of the tumor, the patient’s age and overall health, and the specific findings on the pathology report.
Options the team may consider include:
- Wide local excision — For early-stage disease, the team often discusses wide local excision (surgical removal of the tumor with a margin of surrounding tissue). The extent of surgery depends on the size and location of the tumor and the goal of preserving as much normal vulvar tissue as safely possible.
- Sentinel lymph node biopsy or groin lymph node dissection — For tumors with depth of invasion greater than 1 mm (most stage IB and higher), the team typically discusses lymph node assessment. Sentinel lymph node biopsy is often preferred for early-stage tumors because it provides accurate staging with less surgical morbidity than full groin dissection. Full inguinofemoral lymph node dissection is considered for larger tumors or when sentinel biopsy is not feasible.
- Radiation therapy — May be added after surgery when the pathology report shows high-risk features such as positive margins, positive lymph nodes, extranodal extension, lymphovascular invasion, or perineural invasion. Radiation may also be considered as primary treatment, often combined with chemotherapy (chemoradiation), for locally advanced disease that is not initially resectable.
- Concurrent chemoradiation — For locally advanced disease (typically stage III or IV) or for patients who are not surgical candidates, the team often discusses chemotherapy combined with radiation. This combination is also used after surgery in selected high-risk situations.
- Systemic therapy for advanced or recurrent disease — For metastatic or recurrent disease, the medical oncology team discusses systemic options including chemotherapy and, when applicable, immune checkpoint inhibitor therapy guided by PD-L1 or MMR/MSI testing. Clinical trial enrollment may be discussed because vulvar squamous cell carcinoma is uncommon and standard treatment data for advanced disease are limited.
- Long-term management of underlying skin disease — For patients whose vulvar cancer developed on a background of lichen sclerosus or lichen planus, ongoing dermatologic care to control the underlying inflammation is an important part of overall management.
After treatment, regular follow-up is essential. Surveillance typically includes physical and pelvic examinations every three to six months for the first two to three years, then less frequently. Imaging and additional tests are added based on the original stage, the pathology findings, and the patient’s overall risk of recurrence.
Questions to ask your doctor
- What is the stage of my cancer using both the TNM and FIGO systems?
- What was the size of the tumor and the depth of invasion?
- Was my cancer caused by HPV, or did it develop along the HPV-independent pathway?
- Was p16 or p53 testing performed, and what did the results show?
- What was the histologic grade of my tumor?
- Were the surgical margins negative, close, or positive? Was HSIL or dVIN seen at the margins?
- Was lymphovascular invasion or perineural invasion present?
- How many lymph nodes were examined, and were any involved? Was extranodal extension seen?
- Was PD-L1 or MMR 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?
- Will I need radiation therapy, chemotherapy, or both after surgery?
- How will my underlying skin condition (lichen sclerosus or lichen planus, if present) be managed going forward?
- What follow-up schedule will I have, and what symptoms should prompt me to contact you between visits?
- What is my chance of recurrence, and what can be done to reduce that risk?
- Are there clinical trials available that might be appropriate for my situation?
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