Squamous cell carcinoma of the vagina is a rare but potentially serious cancer that develops in the flat cells lining the vagina. Though uncommon, it represents the majority of vaginal cancers and shares important risk factors with cervical cancer, including infection with certain strains of human papillomavirus.

Epidemiology

Squamous cell carcinoma of the vagina is an uncommon diagnosis in the world of gynecological cancers. It accounts for approximately 80 to 90 percent of all vaginal cancers, yet vaginal cancer itself makes up only about 1 to 2 percent of all gynecological cancers diagnosed in women^[1][2]. This means that primary vaginal cancer, where the disease begins in the vagina rather than spreading from another organ, is quite rare overall.

The disease predominantly affects older women. The average age at diagnosis is around 60 years old^[1][2]. While it is possible for younger women to develop this cancer, particularly those with certain risk factors, it is far more common in women who have gone through menopause. About 1 in 100,000 women are diagnosed with vaginal cancer, with squamous cell carcinoma being the most common type^[2].

Because this cancer is so rare, understanding its patterns and outcomes can be challenging. Much of what is known comes from analyzing smaller groups of patients over time. This rarity also means that many women may never have heard of vaginal cancer until they or someone they know receives a diagnosis.

Causes

The exact cause of squamous cell carcinoma of the vagina is not fully understood, but researchers have identified several important contributing factors. The most significant among these is infection with human papillomavirus, commonly known as HPV. This virus is transmitted through sexual contact and can cause changes in the cells of the vagina over time^[1][2].

HPV is a family of viruses with more than 150 different types. Some of these types, particularly HPV 16 and HPV 18, are considered oncogenic, meaning they have the potential to cause cancer. When these high-risk strains infect the cells lining the vagina, they can lead to abnormal changes. These changes may start as precancerous conditions, where cells are not normal but not yet cancerous either. Over many years or even decades, some of these abnormal cells may develop into squamous cell carcinoma^[6].

It is important to note that most women who are infected with HPV will never develop vaginal cancer. The immune system typically clears the virus from the body within a few years. However, in some women, the infection persists, and the ongoing presence of the virus increases the risk that cell changes will progress to cancer.

Before squamous cell carcinoma develops, there may be precancerous changes in the vaginal tissue. These changes are called vaginal intraepithelial neoplasia, or VAIN. VAIN represents abnormal cells in the lining of the vagina that are not yet cancer but have the potential to become cancer if left untreated^[2][6]. Not all cases of VAIN progress to cancer, and researchers are still working to understand why some do and others do not.

Risk Factors

Several factors can increase a woman’s risk of developing squamous cell carcinoma of the vagina. Understanding these risk factors can help women and their healthcare providers make informed decisions about screening and prevention.

Age is one of the most significant risk factors. The risk of developing this cancer increases as women get older, with most diagnoses occurring in women around age 60 or older^[1][2]. Although younger women can develop vaginal cancer, it is much less common.

Infection with certain strains of HPV is strongly associated with squamous cell carcinoma of the vagina. Because HPV is sexually transmitted, factors that increase the risk of HPV infection also increase the risk of vaginal cancer. These include having sexual intercourse at an early age, having multiple sexual partners over a lifetime, and not being vaccinated against HPV^[1][2].

Smoking is another important risk factor. Women who smoke are about twice as likely to develop vaginal cancer compared to women who do not smoke^[1][2]. The harmful chemicals in tobacco can weaken the immune system and damage cells, making it harder for the body to fight off infections like HPV or repair damaged tissue.

A history of cervical cancer or cervical dysplasia, which are abnormal cells in the cervix, can also increase the risk of vaginal cancer. Women who have been treated for cervical cancer may develop vaginal cancer later, possibly because the same risk factors, such as HPV infection, affect both organs^[1][2].

Other factors that have been linked to an increased risk include alcohol consumption and low socioeconomic status^[1]. Women who have been diagnosed with VAIN, the precancerous condition of the vagina, are at higher risk of developing squamous cell carcinoma if the abnormal cells are not managed or treated^[2].

Symptoms

In its early stages, squamous cell carcinoma of the vagina may not cause any noticeable symptoms. This is one reason why the disease can be difficult to detect early. Many cases are discovered during routine pelvic examinations or Pap tests, even when the woman feels completely well^[1][2].

When symptoms do occur, the most common is vaginal bleeding that is not related to menstruation. This can include bleeding after sexual intercourse or bleeding that occurs in women who have already gone through menopause and no longer have monthly periods^[1][3]. Any unusual bleeding should be evaluated by a healthcare provider, as it can be a sign of various conditions, including cancer.

Some women may notice a lump or mass in the vagina. This mass can sometimes be felt during self-examination or may be discovered during a pelvic exam. The presence of a lump can cause discomfort or pain, especially during sexual intercourse^[1][3].

Vaginal discharge that is not normal is another possible symptom. This discharge may be unusual in color, consistency, or smell, and it may occur without any other explanation^[3].

As the cancer grows or spreads beyond the vagina, additional symptoms may develop. Women may experience pain in the pelvic area, which can be a dull ache or a sharp discomfort. Pain or burning during urination can occur if the cancer has affected the bladder or surrounding tissues. Constipation or difficulty with bowel movements may develop if the cancer is pressing on the rectum^[1][3].

These symptoms are not specific to vaginal cancer and can be caused by many other, less serious conditions. However, any woman experiencing unusual symptoms, particularly abnormal bleeding or a vaginal lump, should seek medical advice promptly.

Prevention

While it is not possible to prevent all cases of squamous cell carcinoma of the vagina, there are several steps women can take to reduce their risk.

Vaccination against HPV is one of the most effective preventive measures. The HPV vaccine protects against the strains of the virus most commonly associated with cervical, vaginal, and other cancers. Health authorities recommend that girls and young women receive the vaccine before they become sexually active, ideally around age 11 or 12, though it can be given to those as young as 9 or as old as 26^[6][22]. The vaccine is also recommended for boys and young men to prevent the spread of HPV and to protect against other HPV-related cancers.

Practicing safer sex can reduce the risk of HPV infection. This includes limiting the number of sexual partners and using condoms, although condoms do not provide complete protection against HPV since the virus can be present on skin not covered by a condom.

Quitting smoking is another important step. Smoking not only increases the risk of vaginal cancer but also affects overall health and the body’s ability to fight infections. Women who smoke should consider seeking help to quit, as this can significantly reduce their cancer risk^[2].

Regular pelvic exams and Pap tests are crucial for early detection. Even though Pap tests are primarily designed to screen for cervical cancer, they can sometimes detect abnormal cells in the vagina. Women who have been treated for cervical cancer or cervical dysplasia should continue to have regular screenings, as they are at higher risk for vaginal cancer^[6].

Managing precancerous conditions like VAIN is also an important preventive measure. If abnormal cells are detected, treatment can prevent them from progressing to cancer. Women diagnosed with VAIN should follow their healthcare provider’s recommendations for monitoring and treatment.

Pathophysiology

Squamous cell carcinoma of the vagina develops in the squamous cells, which are the thin, flat cells that line the surface of the vagina^[1][2]. These cells form a protective layer, similar to the skin on the outside of the body.

The cancer typically begins as a slow, superficial growth within the vaginal wall. In the early stages, the abnormal cells may be confined to the innermost layer of the vaginal lining. Over time, if the cancer is not detected or treated, it can invade deeper into the vaginal tissues. This invasion can affect the muscles and connective tissues that make up the vaginal wall.

As the cancer progresses, it may spread to nearby structures. The vagina is located between the bladder, which stores urine, and the rectum, which is the last part of the digestive tract. If the cancer grows through the vaginal wall, it can reach these adjacent organs, causing symptoms such as painful urination or constipation^[6].

Squamous cell carcinoma of the vagina can also spread through the lymphatic system. Lymph nodes are small, bean-shaped structures that filter fluid and help the body fight infection. Cancer cells can travel through lymphatic vessels to nearby lymph nodes, particularly those in the pelvis and groin. Once cancer reaches the lymph nodes, it has a greater potential to spread to more distant parts of the body^[6].

In some cases, the cancer can metastasize, or spread, to distant organs. The lungs are the most common site for distant spread, although the liver and bones can also be affected^[1]. Metastasis occurs when cancer cells break away from the original tumor, travel through the bloodstream or lymphatic system, and form new tumors in other parts of the body.

The cancer tends to develop in the upper part of the vagina, closest to the cervix, although it can occur anywhere along the vaginal canal^[4]. Because of its slow growth, squamous cell carcinoma of the vagina may remain undetected for a long time, especially if it does not cause symptoms early on.

The progression from normal cells to cancer involves multiple steps. In many cases, persistent infection with high-risk strains of HPV plays a key role. The virus can cause genetic changes in squamous cells that disrupt normal cell growth and division. Over time, these changes accumulate, leading to the development of precancerous lesions like VAIN and, eventually, invasive cancer.