Introduction: Who Should Undergo Diagnostics

Any woman who notices unusual changes in the skin of her vulva should seek medical evaluation. Squamous cell carcinoma of the vulva is the most common type of vulvar cancer, making up about 90% of all cases diagnosed in this area of the body.^[1] This cancer typically develops slowly over several years, often beginning with precancerous changes that doctors can detect before they turn into invasive cancer.^[2]

Women who experience symptoms such as persistent itching, a lump or growth on the vulva, bleeding not related to menstruation, pain or tenderness in the genital area, or changes in the color or thickness of the skin should not delay seeking medical attention.^[3] These symptoms can be signs of vulvar cancer, although they may also indicate other noncancerous conditions. Even if symptoms seem mild or intermittent, it is important to get them checked by a healthcare provider.

Women at higher risk should be particularly attentive to changes in their vulvar area. Risk factors include increasing age, with most cases diagnosed in women aged 65 to 74 years, infection with human papillomavirus (HPV), smoking, inflammatory skin conditions such as lichen sclerosus, prior pelvic radiation, and weakened immune systems.^[4] However, squamous cell carcinoma of the vulva can occur in women without any known risk factors, so all women should remain vigilant about their vulvar health.

Women who have previously been diagnosed with vulvar intraepithelial neoplasia (VIN), a precancerous condition, should undergo regular follow-up examinations. VIN can progress to invasive cancer if left untreated, so ongoing monitoring is crucial to detect any changes early.^[5] Additionally, women with a history of cervical cancer or abnormal Pap smears may have an increased risk of vulvar cancer and should discuss appropriate screening with their doctors.^[6]

Diagnostic Methods

When a woman presents with symptoms that could indicate vulvar cancer, her healthcare provider will begin with a thorough medical history and physical examination. The physical examination includes a careful inspection of the entire vulvar area to look for any visible signs of cancer, such as lumps, sores, color changes, or thickened patches of skin.^[7] The provider will also perform a pelvic exam to check the vagina, cervix, and surrounding structures for any abnormalities.^[8]

If the healthcare provider notices anything suspicious during the physical exam, the next step is often a closer examination using a specialized magnifying instrument called a colposcope. This device allows the doctor to see the vulvar skin in much greater detail, making it easier to identify abnormal areas that might not be visible to the naked eye.^[9] The colposcope shines a bright light on the vulva and magnifies the tissue, helping the doctor distinguish between normal skin and areas that may harbor precancerous or cancerous cells.

The most important diagnostic procedure for confirming squamous cell carcinoma of the vulva is a biopsy. During a biopsy, the doctor removes a small sample of tissue from the suspicious area for examination under a microscope by a specialist called a pathologist.^[10] The pathologist looks at the cells in the tissue sample to determine whether they are cancerous, precancerous, or benign. The type of biopsy performed depends on the size and location of the abnormal area. Some biopsies can be done in the doctor’s office using local anesthesia to numb the area, while others may require a procedure in an operating room under sedation or general anesthesia.^[11]

There are different types of biopsies used in the diagnosis of vulvar cancer. An incisional biopsy involves removing a portion of the abnormal tissue, while an excisional biopsy removes the entire lesion along with some surrounding normal tissue.^[12] The choice of biopsy technique depends on the size and characteristics of the lesion. If the lesion is small, the doctor may opt to remove it completely during the biopsy. If it is large or in a sensitive location, a smaller sample may be taken first to confirm the diagnosis before planning further treatment.^[13]

In some cases, HPV testing may be performed on the biopsy sample to determine whether the cancer is associated with HPV infection. This information can help doctors understand the underlying cause of the cancer and guide treatment decisions.^[14] Approximately 30 to 40% of vulvar cancers are linked to high-risk HPV, particularly in younger women, while the majority of cases in older women are not HPV-related and may be associated with chronic inflammatory conditions of the vulva.^[15]

Once a diagnosis of vulvar cancer is confirmed, additional tests are needed to determine the stage of the cancer, which describes how far the cancer has spread. Staging is essential because it helps doctors plan the most appropriate treatment. Staging tests may include imaging studies such as computed tomography (CT) scans, magnetic resonance imaging (MRI), or positron emission tomography (PET) scans to look for signs that the cancer has spread to nearby lymph nodes or other parts of the body.^[16] A chest X-ray may also be performed to check whether the cancer has spread to the lungs.

An important part of staging is examining the lymph nodes in the groin area, called inguinal lymph nodes. Cancer cells from the vulva can spread to these lymph nodes, so determining whether they are involved is critical for treatment planning.^[17] In some cases, the doctor may perform a sentinel lymph node biopsy, a procedure in which a small number of lymph nodes are removed and examined to see if cancer has spread. If cancer is found in the sentinel lymph nodes, additional lymph nodes may need to be removed.^[18]

Diagnostics for Clinical Trial Qualification

Clinical trials are research studies that test new treatments or combinations of treatments for cancer. Participating in a clinical trial can give patients access to cutting-edge therapies that are not yet widely available. However, to enroll in a clinical trial, patients must meet specific eligibility criteria, which often include particular diagnostic tests and staging results.^[19]

For clinical trials involving squamous cell carcinoma of the vulva, patients typically need to have a confirmed diagnosis based on a biopsy that shows the presence of squamous cell carcinoma. The biopsy report must provide detailed information about the type of cancer, including its grade, which describes how abnormal the cancer cells look under the microscope and how quickly they are likely to grow.^[20]

Staging is another critical requirement for clinical trial enrollment. Trials often specify which stages of cancer are eligible, such as early-stage disease that has not spread beyond the vulva or advanced-stage disease that has spread to lymph nodes or other organs. Imaging studies such as CT scans, MRI, or PET scans are used to determine the stage of the cancer and assess whether the patient meets the trial’s criteria.^[21]

Blood tests are also commonly required as part of the screening process for clinical trials. These tests assess the patient’s overall health and organ function to ensure that they can safely tolerate the investigational treatment. Common blood tests include a complete blood count (CBC) to measure red and white blood cells and platelets, as well as tests of liver and kidney function.^[22]

Some clinical trials for vulvar cancer may require HPV testing to determine whether the cancer is HPV-associated. This information can be important for trials testing treatments that target HPV-related cancers specifically.^[23] Additionally, patients may need to undergo genetic testing or molecular profiling of their tumor to identify specific mutations or biomarkers that are being targeted by the experimental therapy.

Clinical trials may also require patients to have a certain level of physical functioning, often measured using scales such as the Eastern Cooperative Oncology Group (ECOG) performance status. This scale rates a patient’s ability to carry out daily activities and helps determine whether they are healthy enough to participate in the trial. Patients with better performance status are more likely to tolerate intensive treatments and meet the demands of the trial protocol.^[24]

Finally, some trials may have specific exclusion criteria based on previous treatments. For example, a trial testing a new chemotherapy drug may exclude patients who have already received chemotherapy for vulvar cancer, while a trial testing a surgical technique may require that patients have not yet undergone surgery. Understanding these criteria is important for patients and their doctors when considering clinical trial options.^[25]