High grade squamous intraepithelial lesion (HSIL) of the vulva is a precancerous condition caused by persistent infection with human papillomavirus (HPV). It is made up of abnormal squamous cells that are confined to the top layer of the vulvar skin (the epidermis). HSIL can also occur on the mucosal surfaces near the vaginal opening, where the surface layer is called the squamous epithelium rather than skin.
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 vulva.
HSIL of the vulva was previously called “usual-type vulvar intraepithelial neoplasia” or “VIN, usual type,” and is distinct from differentiated vulvar intraepithelial neoplasia (dVIN), which is an HPV-independent precancerous condition with different causes and behavior. HSIL of the vulva is also related to but distinct from low-grade squamous intraepithelial lesion (LSIL) of the vulva, which 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 vulva?
HSIL of the vulva 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 vulvar skin. Over time, viral proteins disrupt the systems that normally regulate cell growth and division, leading to the abnormal changes seen in HSIL.
Several factors increase the risk of developing HSIL of the vulva 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 vulvar HSIL.
- 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 damages cells and is associated with a higher risk of HPV-related precancerous changes.
- Previous HPV-associated disease — A history of cervical, vaginal, or anal precancerous changes or cancer increases the risk of also having HSIL of the vulva, because HPV often affects multiple sites of the lower genital tract.
- Younger age at first HPV infection — Acquisition of HPV at a younger age may increase the chance of persistent infection.
- Lack of HPV vaccination — Vaccination against high-risk HPV types substantially reduces the risk of developing HPV-associated precancerous lesions, including HSIL of the vulva.
What are the symptoms?
Many people with HSIL of the vulva have no symptoms, and the condition is found by chance during a routine examination or because of an unrelated complaint. When symptoms do occur, they may include:
- Itching — The most common symptom. Itching may be mild or persistent and is often the reason someone first seeks evaluation.
- Burning, soreness, or pain — Particularly during intercourse or with friction from clothing.
- A visible bump, plaque, or color change — HSIL of the vulva can appear as raised or flat areas with white, red, brown, or darkly pigmented coloring. Lesions are often multifocal, meaning they occur in more than one location at the same time.
- An ulcer or eroded area — Less commonly, the skin may break down and form a small open area.
Because these symptoms overlap with common, noncancerous vulvar conditions, HSIL is sometimes initially treated as a different problem. Any persistent vulvar symptom or new visible lesion deserves evaluation, especially in someone with a history of cervical HSIL or another HPV-associated condition.
How is the diagnosis made?
The diagnosis of HSIL of the vulva is made by examining a tissue sample under the microscope. Cells or tissue can come from a Pap test, a biopsy, or a larger excision. A biopsy is usually performed by the doctor in the office after a clinical examination, sometimes guided by colposcopy or by applying a dilute acetic acid solution that highlights abnormal areas. The tissue is sent to a laboratory where it is examined by a pathologist.
To confirm the diagnosis and distinguish HSIL from other conditions that can look similar under the microscope, such as dVIN or reactive skin changes, the pathologist often performs a special test called immunohistochemistry. The most important stain in this setting is for a protein called 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 HPV-associated HSIL. dVIN, by contrast, is typically negative or only patchy for p16. Other stains, such as Ki-67 (a marker of cell division) and p53, may also be performed in difficult cases.
HPV testing is not routinely needed to diagnose HSIL of the vulva, because block-type p16 staining is a reliable indicator of high-risk HPV infection. When HPV testing is performed, it almost always shows a high-risk type.
What does HSIL look like under the microscope?
Under the microscope, HSIL of the vulva shows abnormal squamous cells confined to the epidermis or epithelium on the surface of the tissue. Several features help the pathologist recognize HSIL:
- Full-thickness atypia — The abnormal cells extend through more than the lower half of the epidermis or epithelium, and in many cases through nearly the full thickness. This is what distinguishes HSIL from LSIL, in which the abnormal cells are confined to the lower one-third of the epithelium.
- Enlarged, darker nuclei — The cell nuclei are larger than normal and 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 some may have abnormal forms. Mitoses are often seen in the upper layers of the epidermis or epithelium, which is abnormal.
- Cells with HPV-related changes — Some cells may show koilocytes, cells with a clear halo around the nucleus that is characteristic of HPV infection.
- 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 epidermis or 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 on 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 remain in the vulvar skin, increasing the chance that HSIL will return in the same area.
Because HSIL of the vulva is often multifocal and can extend beyond the area that is visible to the naked eye, positive margins are not uncommon. When margins are positive, the team often discusses further surgical treatment or close follow-up.
What is the prognosis?
The prognosis for HSIL of the vulva is generally favorable when it is treated and followed appropriately, but it is a meaningful precancerous condition that should not be ignored. Without treatment, the risk of progression to invasive squamous cell carcinoma over five to ten years is estimated at approximately 5 to 10%. With treatment, the risk of progression is substantially lower, although HSIL can recur within 5 years in 15 to 30% of patients. The risk of progression is meaningfully lower than for dVIN, but still high enough that treatment is generally recommended.
Several features in the pathology report and in the patient’s clinical situation influence the risk that HSIL will recur or progress to invasive cancer:
- 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 vulva 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 the most important predictor of recurrence.
- Immune status — People with weakened immune systems are at higher risk of recurrence and of progression to invasive cancer.
- Smoking — Continued smoking is associated with reduced clearance of HPV infection and a higher risk of HSIL persistence.
- Age — Older patients with HSIL of the vulva have a somewhat higher risk of progression to cancer than younger patients.
- Coexisting HPV-related disease elsewhere — Patients with HPV-related disease in the cervix, vagina, or anal canal may need surveillance of multiple sites because of the field effect of HPV infection.
What happens after this diagnosis?
Because HSIL of the vulva 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 and number of lesions, where on the vulva they are located, the patient’s age and overall health, and whether fertility or sexual function preservation is a priority.
Options that the team may consider include:
- Wide local excision — Surgical removal of the abnormal area with a margin of normal-appearing surrounding skin is the most commonly considered approach. Excision allows the pathologist to confirm the diagnosis, rule out an underlying invasive cancer, and document the margin status.
- Laser ablation — Laser-based treatment can destroy the abnormal area without removing a tissue specimen. It may be considered for multifocal lesions, for lesions in cosmetically or functionally sensitive locations, or for select patients. Because no tissue is sent for pathology evaluation after laser ablation, the team may discuss biopsies before treatment to confirm that no invasive cancer is present.
- Topical imiquimod — Imiquimod is an immune-activating cream that has been used off-label for HSIL of the vulva, particularly for multifocal disease, lesions in young patients, or as an alternative to surgery for select patients. Response rates vary, and recurrence is common.
- Topical 5-fluorouracil — Another topical option used in selected cases, although less commonly than imiquimod.
- Photodynamic therapy — A non-surgical treatment using light activation of a topical photosensitizing agent. It is used in selected cases and at specialized centers.
- Repeat excision for positive margins — When margins are positive, the team may discuss a repeat excision or, depending on the location, close follow-up with examinations every few months.
- 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 and of developing new lesions.
- Smoking cessation — If you smoke, stopping is associated with improved HPV clearance and lower recurrence rates after treatment.
Because HSIL of the vulva can recur and because HPV often affects multiple sites of the lower genital tract, long-term follow-up is essential. Surveillance typically includes regular vulvar examinations and continued cervical cancer screening on the appropriate schedule, with any new symptoms or visible changes evaluated promptly.
Questions to ask your doctor
- Was HSIL the only finding on my biopsy, or were other lesions 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 biopsy, an excision, or a larger surgical 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, age, and overall situation?
- What is the chance that HSIL will come back after treatment?
- What is my chance of developing vulvar 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 those examinations include?
- Should I be screened for HPV-related disease at other sites, such as the cervix, vagina, or anus?
- Should I be vaccinated against HPV if I have not already been vaccinated?
- What lifestyle changes, such as quitting smoking, might reduce my risk of recurrence?
- What symptoms or changes in my skin should prompt me to contact you between scheduled visits?
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