Squamous Cell Carcinoma of the Vulva

Squamous cell carcinoma of the vulva is the most common type of vulvar cancer, accounting for about 90% of all vulvar cancers. This rare disease typically affects older women and often causes visible skin changes, itching, or lumps in the genital area. Early detection and treatment can lead to excellent survival rates.

Table of contents

• What Is Squamous Cell Carcinoma of the Vulva?
• The Vulva: Understanding the Affected Area
• How Common Is This Cancer?
• Signs and Symptoms
• Causes and Risk Factors
• How Vulvar Cancer Develops
• Diagnosis and Testing
• Treatment Options
• Prognosis and Survival
• Prevention

What Is Squamous Cell Carcinoma of the Vulva?

Squamous cell carcinoma of the vulva is a cancer that starts in the squamous cells, which are flat cells found on the surface of the skin^[1]. This type of cancer represents approximately 90% of all vulvar cancers^[2][3]. The cancer develops when cells in the vulva begin to grow and multiply out of control^[4].

Vulvar cancer usually develops slowly over several years. Before invasive cancer appears, precancerous areas of tissue (abnormal cells that may become cancer) typically develop first^[4]. These precancerous lesions are called vulvar intraepithelial neoplasia (VIN)^[4][11].

The Vulva: Understanding the Affected Area

• Labia majora (outer lips)
• Labia minora (inner lips)
• Clitoris
• Opening of the vagina
• Opening of the urethra
• Mons pubis
• Perineum

The vulva is the area of skin that surrounds the opening of the vagina and the tube where urine leaves the body, called the urethra^[1]. It includes the outer lips (labia majora), which are fleshy areas that surround the inner lips, and the inner lips (labia minora), which are tissue folds that surround the vaginal opening^[4]. The vulva also includes the clitoris, the sexually sensitive area above the vaginal opening, and the mons pubis, which is the rounded area in front of the pubic bones that becomes covered with hair during puberty^[4].

About 50% of vulvar squamous cell carcinomas develop on the labia majora, making this the most common location. The labia minora are affected in 15% to 20% of cases^[11]. Less frequently, the cancer can affect the clitoris and Bartholin glands^[11]. In about 5% of cases, lesions can appear in multiple locations^[11].

How Common Is This Cancer?

Vulvar cancer is considered a rare disease. It accounts for approximately 4% of all female genital cancers^[3] and represents only 0.3% of all new cancer cases in the United States^[2]. Healthcare providers diagnose about 6,500 new cases of vulvar cancer in the U.S. each year^[4].

Squamous cell carcinoma of the vulva is most commonly diagnosed in older women. The disease is usually identified between ages 65 and 74, with the median age at diagnosis being 68 to 69 years^[2][4]. Nearly 80% of people diagnosed are over age 50, and over half of all diagnoses occur in people over age 70^[4]. The worldwide incidence is approximately 1.8 per 100,000 women, increasing to 20 per 100,000 after age 75^[3].

Most cases are discovered early in the disease. About 60% of diagnoses are localized, meaning the cancer has not spread beyond the vulva^[2]. However, approximately 30% of patients present with locally advanced disease at the time of diagnosis^[9].

Signs and Symptoms

The first noticeable signs of squamous cell carcinoma of the vulva are usually skin changes on the vulva^[4]. However, in the early stages, vulvar cancer symptoms may not appear at all^[4]. When symptoms do occur, they can include:

• A lump, growth, or wartlike bump on the vulva^[1]
• An open sore or ulcer that doesn’t heal^[1][7]
• Color changes, including skin that looks darker or lighter than usual, or patches of white skin^[4]
• Thickened or rough skin patches^[4]
• Itching of the skin of the vulva that doesn’t go away^[1][3]
• Pain and tenderness that affects the vulva^[1]
• Bleeding in the genital area that isn’t from menstruation^[1]
• A painful or burning sensation^[7]
• Pain during sex or when urinating^[4]

Squamous cell carcinoma of the vulva usually presents as a solitary nodule or ulcer, most often on the labia majora or minora^[3]. The cancer may appear as an ulcerative nodule infiltrating the tissue^[3].

It’s important to see a healthcare provider if you have any of these symptoms. Many of these symptoms are also common in noncancerous conditions, so only a healthcare provider can determine whether these changes are signs of vulvar cancer or a different condition^[4].

Causes and Risk Factors

With vulvar cancer, cells begin multiplying out of control. Without treatment, these cancer cells can spread to other parts of the body^[4]. Several factors can increase a person’s risk of developing squamous cell carcinoma of the vulva:

Increasing age is the most important risk factor for most cancers, including vulvar cancer^[11]. The disease primarily affects older women, particularly those in their sixth through eighth decades of life^[2].

Human papillomavirus (HPV) infection, particularly high-risk types, is a major causative factor in many cases^[2][4]. About 30% to 40% of vulvar cancer cases are associated with high-risk HPV^[2]. HPV infection is linked to the development of vulvar cancer in younger women through its effect on certain proteins in cells that normally control cell growth^[2].

Smoking increases the risk of developing vulvar cancer^[2][3].

Inflammatory conditions of the vulva, particularly lichen sclerosus, are important risk factors^[2][4]. These chronic skin conditions can lead to changes in the vulvar tissue over time.

Other risk factors include:

• Prior pelvic radiation^[2]
• Immunodeficiency (weakened immune system)^[2]
• Having many sexual partners^[11]
• Initiation of sexual intercourse at an early age^[11]
• History of abnormal Pap smears^[11]
• History of genital warts^[2]

How Vulvar Cancer Develops

Squamous cell carcinoma of the vulva typically develops through one of two distinct pathways^[2].

The first pathway involves high-risk human papillomavirus (HPV) infection. This accounts for 30% to 40% of vulvar cancer cases^[2]. HPV has special proteins called E6 and E7 oncoproteins, which interfere with the body’s normal tumor suppressor proteins (p53 and RB). This interference leads to unregulated cell growth and multiplication^[2]. HPV-related vulvar cancers are more common in younger women and are associated with precancerous changes called usual-type VIN^[11].

The second pathway is not related to HPV infection. These cases typically occur in older, post-menopausal women and develop with a background of lichen sclerosus and other chronic skin conditions of the vulva^[9]. This pathway may be associated with a different type of precancerous change called differentiated-type VIN^[11].

There are different morphological variants of squamous cell carcinoma. Basaloid and verrucoid (wartlike) subtypes are related to viral infection and are more common in younger women. About 75% to 100% of basaloid and warty carcinomas contain HPV infection^[11]. In contrast, keratinizing variants (those showing thickened, scaly skin) tend to be HPV-negative and occur in elderly women^[3].

Diagnosis and Testing

Vulvar cancer diagnosis often begins with a physical exam and a discussion of your health history^[10]. The healthcare provider will conduct a pelvic exam to look at the vulva, vagina, cervix, and surrounding organs^[10][11].

A special magnifying device called a colposcope may be used to closely inspect the vulvar area^[1][10]. This instrument allows the doctor to see details that might not be visible to the naked eye.

To confirm the diagnosis, a biopsy is necessary. This procedure involves removing a sample of tissue for testing in a laboratory^[10]. For vulvar cancer, the biopsy involves removing a sample of skin from the suspicious area. A vulvar biopsy may be done in a healthcare provider’s office using medicine to numb the area^[10]. The healthcare professional may use a blade or a circular cutting tool to remove some skin. Sometimes the sample is removed in an operating room under anesthesia^[10].

The tissue sample is sent to a laboratory where a specialist doctor called a pathologist examines it under a microscope^[3]. The pathologist can identify whether cancer cells are present and what type of cancer it is.

If vulvar cancer is diagnosed, additional tests may be needed to determine whether the cancer has spread. These staging tests may include^[10]:

• A more thorough examination of the pelvic area for signs of cancer spread
• Imaging tests such as X-rays, MRI (magnetic resonance imaging), CT (computed tomography), or PET (positron emission tomography) scans to look at the chest, abdomen, or pelvis
• Examination of lymph nodes in the groin area

The stages of vulvar cancer range from 1 to 4. Stage 1 indicates cancer confined to the vulva, while stage 4 indicates cancer that has spread to distant parts of the body^[10].

Treatment Options

Surgery is the main treatment for squamous cell carcinoma of the vulva, especially when the cancer is found early^[2][14][19]. The type of surgery depends on the size and location of the cancer and whether it has spread.

Surgery

Surgical options may involve removing^[14][19]:

• The cancer and an area of healthy tissue around it
• Part of the vulva
• The whole vulva, including the labia and sometimes the clitoris

For tumors diagnosed very early (up to stage T1a), treatment may only require removal of the lesion with at least 1 cm of margin^[3]. From stage T1b onward, when tumors are 2 cm or larger with deeper invasion, treatment may require partial or total vulvectomy (removal of the vulva)^[3].

In many cases, lymph nodes in the groin need to be removed and examined. These are part of the body’s drainage system and are checked to see if cancer has spread^[14][19].

After removing the cancer, the surgeon will repair the vulva using the remaining skin. In some cases, a plastic surgeon will need to reconstruct the vulva using skin or muscle from other parts of the body^[14][19].

Radiation Therapy

Radiotherapy uses high-energy rays of radiation to kill cancer cells^[14][19]. It may be used:

• Before surgery to shrink the cancer
• After surgery to help stop the cancer from coming back
• If surgery is not possible
• If the cancer has spread to other parts of the body

Chemotherapy

Chemotherapy uses medicines to kill cancer cells^[14][19]. Similar to radiation therapy, it may be used:

• Before surgery to shrink the cancer
• After surgery to help stop the cancer from coming back
• If surgery is not possible
• To treat symptoms if the cancer has spread

In cases of locally advanced disease, a combination of chemotherapy and radiation (chemoradiation) may be recommended^[9]. This approach is an effective treatment that can minimize the need for extensive surgery^[9].

Advanced Cancer

Approximately 30% of women present with advanced disease at diagnosis^[9]. If cancer is advanced and cannot be cured, treatment aims to slow down the growth and spread of the cancer, help with symptoms, and help patients live longer^[14][19]. A symptom control team or palliative care team will help manage symptoms and provide support^[14][19].

Prognosis and Survival

The prognosis for squamous cell carcinoma of the vulva depends largely on whether the cancer has spread to the lymph nodes and whether it has invaded adjacent structures^[11].

For patients with early-stage, localized disease (cancer that has not spread beyond the vulva), the outlook is very good. About 60% of diagnoses are localized^[2], and these patients have an 85% five-year survival rate^[2].

In patients with operable disease without lymph node involvement, the overall survival rate is 90%^[11]. Tumors diagnosed very early, up to stage T1a, have survival rates at five and ten years of around 100% and 94.7%, respectively^[3].

However, when the cancer has spread to the lymph nodes, the prognosis is less favorable. In patients with nodal involvement, the 5-year overall survival rate is approximately 50% to 60%^[11].

The size of the primary tumor is less important in determining prognosis than lymph node status^[11]. The earlier vulvar cancer is diagnosed, the less likely an extensive surgery is needed for treatment^[1].

Prevention

While not all cases of squamous cell carcinoma of the vulva can be prevented, several steps can reduce your risk:

HPV vaccination can protect against high-risk types of human papillomavirus that are linked to vulvar cancer^[4]. This is particularly important for younger individuals before they become sexually active.

Avoiding smoking is important, as smoking is a known risk factor for vulvar cancer^[2][3].

Regular gynecological check-ups can help detect precancerous changes early. Since vulvar cancer and its precursors may be associated with HPV infections, women should follow screening recommendations, including cervical cancer screening^[11].

Monitoring chronic vulvar conditions such as lichen sclerosus is important. If you have these conditions, follow your healthcare provider’s recommendations for treatment and regular monitoring.

Because vulvar intraepithelial neoplasia (VIN) can develop into vulvar cancer, it is important to get treatment for VIN if diagnosed^[11].

If you notice any changes in the vulvar area, including skin color changes, lumps, sores, or persistent itching, see your healthcare provider promptly. Early detection can significantly improve treatment outcomes^[1][4].