What Causes Vaginal Intraepithelial Neoplasia?

Medically Reviewed on 12/10/2021
vaginal intraepithelial neoplasia
Vaginal intraepithelial neoplasia (VAIN) is typically caused by human papillomavirus (HPV), as well as immunosuppression and cancerous conditions.

Vaginal intraepithelial neoplasia (VAIN) is caused by the following conditions:

Human papillomavirus (HPV)

HPV is the most common cause of VAIN and has more than 100 subtypes, among which 30 subtypes can affect the genitals, and among those, 13 are considered high-risk HPV. High-risk subtypes HPV 16 and HPV 18 are mostly associated with VAIN.

HPV is the most common virus that affects almost everyone at some point in their life. It may not cause any harm to the body and does not produce any symptoms. Usually, HPV is eliminated spontaneously by the body's immune system. Due to this, the majority of individuals may never know the presence of HPV.

If a person’s immune system does not clear HPV, it remains in the body. If the vagina is infected with HPV, it may damage the vaginal epithelium and develop into VAIN.

HPV is transmitted in two ways:

  1. Sexual transmission: HPV is mostly transmitted through sexual contact, both vaginal and anal, with an infected person. Having multiple sexual partners increases the risk of HPV.
  2. Nonsexual transmission: The virus may have a nonsexual transmission, where it spreads when the infected skin of a patient with HPV comes in direct contact with a broken skin of a healthy person.


Factors that reduce the immunity of the body such that the body may not eliminate HPV increases the risk of VAIN, including:

Cancer or precancerous conditions

Having a precancerous condition or cancer in the vagina, cervix, vulva, or other reproductive and pelvic tissue may increase the risk of VAIN.

Patients who underwent hysterectomy for cervical intraepithelial neoplasia (CIN), a condition caused by HPV, may develop VAIN. This may be a result of the extension of CIN into the vagina that was left undetected and untreated. The incidence of VAIN is less than cervical or valvular dysplasia.

Prior treatment with radiotherapy for cancer in the pelvic region may increase the risk of VAIN.

What is VAIN?

Vaginal intraepithelial neoplasia (VAIN) is the presence of abnormal cells in the lining (epithelium) of the vagina. VAIN is a precancerous condition that may develop into cancer over a period. It begins in the vagina, which is also known as the birth canal.

Although VAIN may be seen in women of all ages, it is mostly seen in women who are older than 50 years. These abnormal changes in the cells may be seen in other areas such as the vulva, cervix, and anus, along with the vagina.

Early detection of the condition and providing treatment may prevent the cells from converting into cancer. However, patients with mild VAIN may recover without any treatment.

What are the risk factors for VAIN?

Risk factors for vaginal intraepithelial neoplasia include:

  • Human papillomavirus infection
  • Prior history of vulvar intraepithelial neoplasia
  • Prior history of cervical intraepithelial neoplasia
  • History of cervical and vulvar cancer
  • Use of tobacco
  • Being immunocompromised

Grading of VAIN

Studying a sample of the vaginal tissue in the lab tells us the severity of the vaginal intraepithelial neoplasia (VAIN).

Based on the distribution of the abnormal cells, VAIN is classified into the following:

VAIN I (low grade)

  • VAIN I is a low-grade squamous intraepithelial lesion or mild dysplasia (presence of abnormal cells).
  • Nuclear pleomorphism (different sizes and shapes of the nucleus are seen in cells of the same tissue) and hyperchromasia (dark nucleus) are seen in 33 percent of the thickness of the vaginal lining. These nuclear changes represent precancerous conditions.

VAIN II and III (high grade)

  • VAIN II is a high-grade squamous intraepithelial lesion or moderate dysplasia.
  • VAIN III is a high-grade squamous intraepithelial lesion or severe dysplasia/squamous carcinoma in situ (cancer within abnormal cells, not spread to surrounding normal healthy tissue).
  • Nuclear pleomorphism and hyperchromasia if seen in the 66 percent of the thickness of the vaginal lining come under VAIN II, and if the full thickness of the vaginal lining is involved, it comes under VAIN III.
  • Atypical mitotic figures (a dividing cell that has generated an unusually large quantity of genetic material) are seen in the cells.
  • Koilocytosis is seen in the epithelium. Human papillomavirus infection transforms normal cells into koilocytes, which are referred to as halo cells, and this condition is known as koilocytosis.


The vagina includes the labia, clitoris, and uterus. See Answer

What are the symptoms of VAIN?

Vaginal intraepithelial neoplasia is mostly asymptomatic. However, individuals may have postcoital spotting or vaginal discharge. Some patients, who possibly have low immunity, may develop genital warts.

How to diagnose VAIN

Vaginal intraepithelial neoplasia (VAIN) is diagnosed in the following ways:

  • Physical examination:
    • The gynecologist uses a special device known as a colposcope to examine the entire vagina.
      • They may palpate the vaginal wall for possible lesions, color changes, ulceration, and thickness or irregularity.
      • The majority of VAIN lesions are seen in the top 33 percent of the vagina, and more than half of patients have numerous lesions. 
      • Application of three to five percent acetic on lesions may show elevated or flat white, granular epithelium with strongly marked boundaries, punctation, and mosaic pattern.
      • This is seen mostly in high-grade VAIN.
    • The appearance of a substantially uneven surface or severe vascular anomalies with peculiar branching indicates an invasive condition that requires an excisional biopsy.
      • Before excision, Schiller's or Lugol's iodine solution can be used to locate lesions and confirm borders.
  • Pap smear:
    • Also known as a liquid-based cytology test, the doctor collects a sample of cells from the cervix using a little brush. It is usually not painful and does not require the use of anesthesia.
  • Biopsy:
    • A small part of the tissue is removed from the vagina.
      • Because it is a painful procedure, a local anesthetic agent is administered before the procedure.
      • There may be a chance of bleeding during this procedure, but with the use of Monsel's solution or silver nitrate, the bleeding is stopped. 
      • However, if the bleeding continues, a suture may be required.
      • This is a small outpatient procedure that does not require any hospital admission.
    • The removed tissue is sent to the lab for analysis and detection of any possible anomaly.

What are the treatment options for VAIN?

Mild cases of vaginal intraepithelial neoplasia (VAIN) are usually self-limiting and do not require any active management. However high-grade VAIN is to be treated right away to prevent the formation of cancer.

The treatment varies from one patient to another because it depends on the size, location, and severity of the condition.

Other factors that contribute to selecting the proper treatment include:

  • Age of the patient
  • Conditions of the vagina
  • Prior history of hysterectomy
  • History of radiotherapy
  • Status of the sexual activity
  • Other comorbidities

Various treatments include:


Ablation is the removal or destruction of unwanted body tissue and is done by using various methods:

  • Laser ablation: This method is also known as laser vaporization. It uses a laser beam to burn VAIN. It is a small outpatient procedure that is done while the patient is sedated. Because this is an outpatient operation, most patients may go home the same day.
  • Carbon dioxide laser treatment: This process involves directing a small, high-energy laser beam toward the cells and eliminating them. It is usually done under general anesthesia; however, if the affected vaginal surface area is limited, it can be done under local anesthesia. If the doctor believes there is a substantial danger that the illness may recur, they may treat the entire vagina with topical 5-fluorouracil and CO2 laser therapy.
  • Diathermy treatment: Diathermy, commonly known as “deep heat,” is a therapy that includes applying high-frequency electrical current to the affected region with an ultrasonic, shortwave, or microwave device. Following the procedure, the patient may notice some minor bleeding or vaginal discharge for the first three to five days, which is usually normal. It is recommended to avoid intercourse and avoid putting anything into the vagina, including tampons and douches, for four to six weeks after the procedure.
  • Internal radiation: Internal radiation is not recommended for most cases of VAIN, but it is considered beneficial in treating recurrent or extensive VAIN. A small tampon-shaped device that contains radioactive substance is placed in the vagina, and it is left there for a few hours to days to eliminate the abnormal cells.


If there is a potential of undiagnosed malignancy in the region or the case of VAIN is recurrent, the doctor may propose surgery.

For the treatment of VAIN, there are two basic surgical methods. The surgeon will remove the aberrant cells and some good tissue around them. This is known as a broad local excision.

  • Local excision: The affected tissue is surgically removed, along with some normal tissue surrounding the affected area to prevent any possible spills of the abnormal cells. The healthy tissue around the affected tissue is referred to as the buffer zone. If the buffer zone is left intact and if it has any abnormal cells, it may lead to a recurrence of the condition. After the surgery, the vagina may be modified or stretched to allow the patient to continue having vaginal intercourse.
  • Partial or total vaginectomy: It is the removal of part or complete vagina, and the surgeon may use tissue from the surrounding areas to create a new functional vagina.

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Medically Reviewed on 12/10/2021
Image Source: iStock Images

Vaginal Intraepithelial Neoplasia: https://www.uptodate.com/contents/vaginal-intraepithelial-neoplasia#H591594050

Vaginal Intraepithelial Neoplasia: https://www.rogelcancercenter.org/gynecologic-cancers/prevention/pre-cancerous-conditions/vaginal-intraepithelial-neoplasia

Vaginal Intraepithelial Neoplasia: https://www.sciencedirect.com/topics/medicine-and-dentistry/vaginal-intraepithelial-neoplasia