Vulvar Intraepithelial Neoplasia (VIN) is a complex precancerous skin condition that affects the vulvar skin. VIN is not cancer but when cellular changes occur in the vulvar skin. It can range from mild to severe, and as a precancerous condition, if the changes become more severe, cancer of the vulva may develop.
Because VIN and lichen sclerosus (LS) are associated, LS patients must understand the stages of VIN and how to prevent its progression to cancer. Let's review the data around VIN and explore strategies for prevention.
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What Are the Categories and Stages of Vulvar Intraepithelial Neoplasia (VIN)?
There are two main types of VIN:
Usual or Classical Vulvar Intraepithelial Neoplasia (VIN)
VIN is the more common type, divided into two categories:
- Low-Grade Squamous Intraepithelial Lesion (LSIL) - Previously referred to as VIN 1, it's often caused by certain types of HPV infections that can cause warts but are not cancerous. These lesions may go away on their own or may require regular check-ups.
- High-Grade Squamous Intraepithelial Lesion (HSIL) - Previously known as VIN 2 and VIN 3, this type of classical VIN is typically caused by high-risk HPV infections. These lesions are treated as they are at an increased risk of becoming cancerous over time.
Differentiated Vulvar Intraepithelial Neoplasia (dVIN)
Differentiated VIN is less common and tends to affect older women but can develop in women of any age. Unlike HSIL and LSIL, dVIN is not related to HPV infection but is often associated with lichen sclerosis and chronic inflammation of the vulvar skin. dVIN carries a higher cancer risk than HSIL, and doctors frequently prescribe more aggressive treatment to prevent vulvar cancer. (1)
A systematic review of the vulvar cancer risk associated with dVIN published in 2021 confirmed that patients with dVIN have a high risk of rapid cancer progression, highlighting the importance of clinical awareness and prompt diagnosis and treatment. (2)
Another study also included an Unclassifiable VIN, which is any VIN that cannot be classified in the other two categories and often includes rare types, such as Pagetoid VIN. (3)
To gain a better understanding, I suggest you check out the simple, practical illustration on the Cancer Research UK VIN info page that demonstrates the abnormal cell growth seen in VIN and how it impacts the different layers of skin. (1)
VIN and Lichen Sclerosus
Research has shown a notable connection between the chronic inflammation present in LS and the progression to Vulvar Intraepithelial Neoplasia. To begin to understand this connection, I will take a moment to review the several dermal layers present in vulvar skin. (4)
Epidermis—This is the outermost layer of the skin that acts as a protective barrier. It consists of several sub-layers, including the basal layer, the one closest to the dermis, and the squamous cell layer, a layer of skin 5-10 cells thick that overlies the basal cell layer. The epidermis comprises different types of cells, notably melanocytes, Langerhans cells, and keratinocytes, which produce keratin, a structural protein.
Dermis - Beneath the epidermis lies the dermis, which contains blood vessels, sweat glands, hair follicles, and connective tissue. It provides support, nourishment, and blood supply to the epidermis.
Subcutaneous Tissue (Subcutis) - The deepest layer of the vulvar skin is known as subcutaneous tissue. It contains fat cells, blood vessels, and nerves. This layer helps insulate and cushion the vulvar area.
The Inflammation Connection
Lichen Sclerosus primarily affects the epidermal and dermal layers of the vulvar skin. It is characterized by specific skin changes, including the thinning of the epidermis, making the skin more vulnerable to damage and irritation, a loss of elasticity that makes the skin tighter and less flexible, often leading to discomfort and pain during sexual activity, and hyperkeratosis, or a thickening of the outer layer of epidermis that causes the textbook white and shiny plaques of LS.
The other component of LS is chronic inflammation and immune cell infiltration. Chronic inflammation in LS is characterized by immune cells in the affected skin layers, like lymphocytes and macrophages. These immune cells release inflammatory molecules and cytokines, contributing to ongoing inflammation and tissue damage. This chronic inflammation likely has a link to underlying autoimmunity. (5)
So, how does that link to VIN? Though the connection is not fully understood, chronic inflammation can disrupt normal cellular processes, causing tissue damage, including thinning and scarring. It also increases the risk of genetic mutations, and this combination of chronic inflammation, tissue damage, and mutations may create a vulvar microenvironment conducive to the development of abnormal cell growth. Further, the LS-associated immune dysfunction that leads to the persistence of inflammation directed at healthy tissue may lead to immune cells that do not adequately deal with unhealthy cells, potentially contributing to the precancerous changes seen in dVIN.
What’s the True VIN and Cancer Risk for Lichen Sclerosus Patients?
A longitudinal study published in Cancer Epidemiology, Biomarkers & Prevention in 2016, which included over 3,000 women with histologically-proven LS, looked at the incidence and risk of Vulvar Squamous Cell Carcinoma (VSCC), the skin cancer most commonly associated with LS and dVIN, and found the cumulative incidence of VSCC in women with LS as follows:
- Follow-up after five years - 2.1%
- Follow-up after ten years - 3.3%
- Follow-up after 15 years - 4.1%
- Follow-up after 20 years - 6.7% (6)
The study noted that the 10-year cumulative incidence of VSCC in patients with LS and concurrent VIN at baseline exam was significantly higher at 18.8% than those without VIN at baseline at 2.8%. (6) Researchers concluded that though risk factors for cancer development remain largely unknown, contributing factors include an individual patient’s response to corticosteroid treatment, immune status, smoking, genetic predisposition, and epigenetic events. Given the higher rates of VSCC in women with LS, it was advised that all women with vulvar LS should be regularly monitored for skin changes, disease progression, and the development of VIN.
Preventing VIN Progression
Here are some scientifically backed methods and strategies to reduce LS's risk of progressing to VIN and VSCC.
Topical Corticosteroids - high-potency topical corticosteroids, such as clobetasol propionate, are the gold standard in LS management and effectively control the inflammation associated with LS and reduce the risk of developing VIN. (7) Read more about steroid therapy here.
Regular Medical Follow-ups—As mentioned previously, women with LS, especially those with VIN or a history of VIN, should undergo regular check-ups with their healthcare providers. These visits allow for early detection and management of any changes or abnormalities.
Diet and Lifestyle Modifications - while studies have looked at the links between diet and the development of gynecologic cancers (8), speaking from both personal and clinical experience, diet changes can effectively address underlying autoimmunity and inflammation, supporting overall health. (9)
Safe Sex Practices - practicing safe sex and using protection can reduce the risk of sexually transmitted infections (STIs), which may contribute to vulvar irritation and inflammation. STI preventative measures can also help prevent HPV infection, which is also directly associated with VIN.
Quit Smoking - smoking, a well-known carcinogenic, has been linked to an increased risk of VIN and vulvar cancer, so quitting can lower your risk. (10)
Understanding VIN and its association with Lichen Sclerosus is very important. While a relatively small percentage of LS cases may progress to VIN or vulvar cancer, early detection and prevention strategies are critical.
As a lichen sclerosus and vulvar cancer patient myself, I know just how scary and anxiety-producing these conditions can be. LS requires a lot of maintenance and monitoring of your skin for any unusual changes, and this level of upkeep and hypervigilance can seriously impact your mental health and well-being. (11)
If you are in a good, information-seeking place along your healing journey, and you have a support network that includes caring health practitioners, a community of other LS patients, family, and friends, this study published in 2022 contains a lot of graphic visuals **Trigger Warning** that can help you inform and educate yourself on the various dermatological conditions that can affect your vulva, including what various VIN lesions and vulvar cancers may present as or look like. (12, 13)
Please ensure you are in a positive mental space if you decide to view and educate yourself further. Otherwise, don't hesitate to have a doctor investigate if you are suspicious of any vulvar changes or anything you’re concerned about. Knowledge is power, your health and well-being matter, and you will always be your best health advocate!
Sources:
- Vulval intraepithelial neoplasia (VIN). Vulval cancer. Cancer Research UK. Available at: https://www.cancerresearchuk.org/about-cancer/vulval-cancer/vulval-intraepithelial-neoplasia
- Voss FO, Thuijs NB, Vermeulen RFM, Wilthagen EA, van Beurden M, Bleeker MCG. The Vulvar Cancer Risk in Differentiated Vulvar Intraepithelial Neoplasia: A Systematic Review. Cancers (Basel). 2021 Dec 7;13(24):6170. doi: 10.3390/cancers13246170.
- Ramírez M, Andía D, Bosch JM, Cararach M, Coronado P, de Sanjosé S, et al. AEPCC Guidelines. 2015; 1-39. ISBN 978-84-608-3825-8. Available at:
https://www.aepcc.org/wp-content/uploads/2019/02/AEPCC_guidelines-VIN_en_2102019.pdf - Kolarsick P, Kolarsick MA, Goodwin C. Anatomy and Physiology of the Skin. JDNA. 2011 Jul;3(4):203-213. Available at: https://www.ons.org/sites/default/files/publication_pdfs/SkinCancer.pdf
- De Luca DA, Papara C, Vorobyev A, Staiger H, Bieber K, Thaçi D, et al. Lichen sclerosus: The 2023 update. Front Med (Lausanne). 2023 Feb 16;10:1106318. doi: 10.3389/fmed.2023.1106318.
- Bleeker MC, Visser PJ, Overbeek LI, van Beurden M, Berkhof J. Lichen Sclerosus:
Incidence and Risk of Vulvar Squamous Cell Carcinoma. Cancer Epidemiol Biomarkers Prev. 2016 Aug;25(8):1224-30. doi: 10.1158/1055-9965.EPI-16-0019. - Singh N, Mishra N, Ghatage P. Treatment Options in Vulvar Lichen Sclerosus: A Scoping Review. Cureus. 2021 Feb 24;13(2):e13527. doi: 10.7759/cureus.13527.
- Koshiyama M. The Effects of the Dietary and Nutrient Intake on Gynecologic Cancers. Healthcare (Basel). 2019 Jul 7;7(3):88. doi: 10.3390/healthcare7030088.
- Cooan H. Lichen Sclerosus and Diet: Comprehensive Guide. Lichen Sclerosus Support Network. Accessed August 15, 2023. Available at:
https://lssupportnetwork.org/lichen-sclerosus-and-diet-comprehensive-guide/ - Bucchi L, Pizzato M, Rosso S, Ferretti S. New Insights into the Epidemiology of Vulvar Cancer: Systematic Literature Review for an Update of Incidence and Risk Factors. Cancers (Basel). 2022 Jan 13;14(2):389. doi: 10.3390/cancers14020389.
- A Look at Acceptance and Resilience. What Does It Mean? Lichen Sclerosus Support Network. Published August 22, 2023. Accessed September 5, 2023. Available at: https://lssupportnetwork.org/a-look-at-acceptance-and-resilience-what-does-it-mean/
- The Lost Labia Journey: Finding Community. Lichen Sclerosus Support Network. Published March 5, 2021. Accessed September 6, 2023. Available at: https://lssupportnetwork.org/the-lost-labia-journey-finding-community/
- Kesić V, Vieira-Baptista P, Stockdale CK. Early Diagnostics of Vulvar Intraepithelial Neoplasia. Cancers (Basel). 2022 Apr 4;14(7):1822. doi: 10.3390/cancers14071822.
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