High grade squamous intraepithelial lesion (HSIL) of the vagina is a precancerous condition caused by infection with human papillomavirus (HPV). It is composed of abnormal squamous cells that have been infected and altered by the virus. These cells are part of the epithelium, the thin surface layer of tissue that lines the inside of the vagina. Most cases are caused by high-risk HPV types, particularly HPV16, which accounts for the large majority of cases. Other high-risk types involved include HPV18, HPV31, HPV33, and HPV45.
HSIL is not cancer, but if left untreated, it can progress over time to squamous cell carcinoma of the vagina. For this reason, most patients with HSIL are offered treatment to remove the abnormal area. HSIL of the vagina is also called high-grade vaginal intraepithelial neoplasia (VaIN), and in older reports, it may be described as VaIN 2 or VaIN 3. It is distinct from low grade squamous intraepithelial lesion (LSIL) of the vagina, a related condition that also is caused by HPV but carries a much lower risk of progressing to cancer.
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 HSIL of the vagina?
HSIL of the vagina is caused by persistent infection with high-risk HPV. HPV is a very common virus that spreads through skin-to-skin contact, including sexual contact. Most HPV infections clear on their own within one to two years, but in some people, the infection persists in the cells of the vaginal lining. Over time, viral proteins disrupt the systems that normally control how cells grow and divide, leading to the abnormal changes seen in HSIL.
Several factors increase the risk of developing HSIL of the vagina or of having an existing HSIL that persists rather than resolves:
- Persistent high-risk HPV infection — The single most important risk factor. HPV16 is the type most commonly associated with vaginal HSIL.
- Previous or current HPV-related disease of the cervix or vulva — HSIL of the vagina is strongly associated with a history of cervical or vulvar precancerous changes or cancer, because HPV often affects more than one site of the lower genital tract. Many cases are found in patients who have previously been treated for cervical disease, including those who have had a hysterectomy.
- A weakened immune system — Conditions such as HIV infection, organ transplantation, or long-term immunosuppressive therapy make it harder for the body to clear the virus.
- Cigarette smoking — Smoking is associated with a higher risk of HPV-related precancerous changes.
- Previous pelvic radiation therapy — Radiation to the pelvis, for example, as treatment for another cancer, has been associated with an increased risk of vaginal HSIL.
What are the symptoms?
Most people with HSIL of the vagina have no symptoms, and the condition is found during a Pap test or examination performed for another reason, often as part of follow-up after treatment for cervical disease. When symptoms are present, they may include unusual vaginal discharge, vaginal bleeding (including bleeding after intercourse), or, less commonly, vaginal discomfort. Because HSIL usually causes no symptoms, regular screening and examination, particularly in patients with a history of HPV-related disease, is the most reliable way to detect it.
How is the diagnosis made?
The diagnosis of HSIL of the vagina is made by examining cells or tissue under the microscope. The process often begins with an abnormal Pap test or a positive HPV test. This is usually followed by colposcopy, an examination of the vagina using a magnifying instrument called a colposcope, sometimes after applying a dilute acetic acid solution that highlights abnormal areas. A small tissue sample, called a biopsy, is then taken from any abnormal area and sent to the laboratory, where it is examined by a pathologist.
To confirm the diagnosis and distinguish HSIL from other conditions that can appear similar under the microscope, the pathologist often performs a special test called immunohistochemistry for the protein p16. In HSIL caused by high-risk HPV, p16 shows strong, continuous “block-type” staining throughout the affected area. Block-type p16 staining is one of the most important features supporting the diagnosis of HSIL. Conditions that can resemble HSIL, including reactive or reparative changes, are typically negative or only patchy for p16.
What does HSIL of the vagina look like under the microscope?
Under the microscope, HSIL of the vagina shows abnormal squamous cells confined to the epithelium, the surface layer of tissue lining the vagina. Several features help the pathologist recognize HSIL:
- Abnormal cells through much of the epithelium — The abnormal cells extend through more than the lower half of the epithelium, and in many cases through nearly its full thickness. This is what distinguishes HSIL from LSIL, in which the abnormal cells are confined to the lower one-third.
- Enlarged, darker cells — The abnormal cells are larger than the surrounding normal cells, and their nuclei appear darker, a feature called hyperchromasia. The cells often vary in size and shape.
- Many dividing cells — Mitotic figures (cells in the process of dividing) are common and may be seen in the upper layers of the epithelium, which is abnormal.
- Block-type p16 staining — Strong, continuous “block-type” p16 staining throughout the affected area confirms the HPV-driven nature of the lesion.
- Confinement to the epithelium — Importantly, the abnormal cells stay confined to the surface epithelium and do not invade into the deeper tissue. This is what makes HSIL precancerous rather than cancer.
Surgical margins
A margin is the cut edge of tissue removed during a surgical procedure, such as an excision. After surgery, the pathologist examines the margins under the microscope to determine whether any abnormal cells are present at the cut edges of the tissue. Margins are reported only when an excision has been performed to remove the entire lesion; they are not reported for a small biopsy taken solely for diagnosis.
- Negative margin — No HSIL cells are present at the cut edge of the tissue. This suggests that the abnormal area was completely removed.
- Positive margin — HSIL cells are present at the cut edge. This means some abnormal cells may still remain in the vaginal lining, which increases the chance that HSIL will return in the same area.
Because HSIL of the vagina is often multifocal (present in more than one area) and the vagina is a difficult surface to treat completely, positive margins are not uncommon. When margins are positive, the team often discusses further treatment or close follow-up.
What is the prognosis?
The prognosis for HSIL of the vagina is generally favorable when it is treated and followed appropriately, but it is a meaningful precancerous condition that should not be ignored. Without treatment, HSIL of the vagina can progress to vaginal squamous cell carcinoma; published estimates of this risk vary but are generally in the range of a few percent up to about 10%. With treatment, the risk of progression is lower, although HSIL of the vagina can recur after treatment, and ongoing monitoring is important.
Several features influence the risk that HSIL will recur or progress:
- Margin status — Negative margins on an excision specimen are associated with the lowest risk of recurrence. Positive margins increase the chance of residual disease.
- Multifocal disease — HSIL of the vagina is frequently multifocal, with several separate areas of involvement. Multifocal disease is more difficult to treat completely and has a higher recurrence rate.
- Persistent high-risk HPV infection — Continued presence of high-risk HPV after treatment is an important predictor of recurrence.
- Immune status — People with weakened immune systems are at higher risk of recurrence and of progression to invasive cancer.
- Previous HPV-related disease — A history of cervical or vulvar HPV-related disease reflects an ongoing tendency for HPV to affect the lower genital tract, and these patients require continued surveillance of multiple sites.
What happens after this diagnosis?
Because HSIL of the vagina is a treatable precancerous condition with a meaningful risk of progression to cancer, the gynecologic team will discuss treatment options with the patient. The choice depends on the size, number, and location of the lesions, whether the patient has had previous treatment to the vagina or cervix, and the patient’s overall health.
Options that the team may consider include:
- Surgical excision — Removal of the abnormal area allows the pathologist to confirm the diagnosis, rule out an underlying invasive cancer, and document the margin status. Excision is often used when invasion cannot be ruled out or when the lesion is located at the top of the vagina.
- Laser ablation — Laser treatment can destroy the abnormal area without removing a tissue specimen. It may be considered for multifocal lesions or for lesions in locations that are difficult to remove surgically. Because no tissue is sent for pathology evaluation after laser ablation, the team usually confirms with biopsies beforehand that no invasive cancer is present.
- Topical treatments — Creams applied inside the vagina, such as imiquimod or 5-fluorouracil, are used in selected cases, particularly for multifocal disease or as an alternative to surgery for some patients.
- Radiation therapy (brachytherapy) — Internal radiation placed inside the vagina may be considered for extensive or recurrent disease, or for patients who are not good candidates for surgery.
- Observation in selected cases — For small lesions in certain situations, close monitoring may be discussed as an alternative to immediate treatment.
- HPV vaccination — If you have not already received the HPV vaccine, the team may discuss vaccination. Vaccination after diagnosis does not treat existing HSIL but may reduce the risk of acquiring new HPV infections.
Because HSIL of the vagina can recur and because HPV often affects multiple sites of the lower genital tract, long-term follow-up is essential. Surveillance typically includes regular examinations and continued screening, with any new symptoms or visible changes evaluated promptly.
Questions to ask your doctor
- Was HSIL the only finding, or were other abnormal areas present?
- Was high-risk HPV identified, and if so, which type?
- Was p16 staining performed, and what did the result show?
- Was the HSIL found on a Pap test, a biopsy, or a larger excision specimen?
- If an excision was done, were the margins negative or positive?
- Is there evidence of multifocal disease (more than one area involved)?
- What treatment options would you discuss with me based on my pathology findings?
- What is the chance that HSIL will come back after treatment?
- What is my chance of developing vaginal cancer over the coming years, and what can be done to reduce that risk?
- How often will I need follow-up examinations, and what should they include?
- Should I also be checked for HPV-related changes in my cervix or vulva?
- Should I be vaccinated against HPV if I have not already been vaccinated?
- Would quitting smoking reduce my risk of recurrence?
- What symptoms or changes should prompt me to contact you between scheduled visits?
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