What is the risk of cancer associated with lichen sclerosis?

Cancer Risk Associated with Lichen Sclerosus

Lichen sclerosus carries a significant risk of developing squamous cell carcinoma (SCC), with approximately 4-5% of patients with genital lichen sclerosus developing malignancy during their lifetime. 1

Cancer Risk by Gender and Location

Female Patients

• Risk level: 4-5% lifetime risk of vulvar SCC 1
• Evidence in tissue samples: Approximately 60% of vulvar SCCs occur on a background of lichen sclerosus 1
• Risk factors that increase malignancy potential:
  • Advanced age
  • Presence of vulvar intraepithelial neoplasia (VIN)
  • Long history of lichen sclerosus
  • Delayed diagnosis
  • Poor compliance with topical corticosteroid treatment 2

Male Patients

• Risk level: 2-8% lifetime risk of penile SCC, with most studies suggesting around 4-5% 1
• Evidence in tissue samples: Histological evidence of lichen sclerosus can be found in 23-40% of penile carcinomas 1
• Specific findings: In a 10-year multicenter cohort of 130 male patients with genital lichen sclerosus, histological changes of SCC were found in 8 patients, verrucous carcinoma in 2, and penile intraepithelial neoplasia in 1 1

Extragenital Lichen Sclerosus

• Cancer risk: No increased risk of malignancy has been documented in extragenital lichen sclerosus 1

Pathogenesis of Malignant Transformation

Two distinct pathogenetic mechanisms for genital SCC have been identified:

1. HPV-associated pathway: Occurs in younger patients, associated with oncogenic types of human papillomavirus (HPV16 and HPV18)
2. Chronic inflammation pathway: Occurs in older patients with chronic scarring dermatoses like lichen sclerosus, with limited evidence of HPV involvement 1

Additional factors contributing to malignant transformation:

• Oxidative stress: Causes DNA damage and lipid peroxidation, contributing directly to malignant transformation 3
• Chronic inflammation: Long-standing inflammation leads to tissue damage that may promote carcinogenesis 1
• Disease reactivation: Occurrence of a prominent lichenoid infiltrate on long-standing chronic lichen sclerosus suggests disease reactivation that has been linked with penile SCC 1

Monitoring and Prevention

Biopsy Recommendations

• Initial diagnosis: Biopsy is recommended in all patients suspected of having lichen sclerosus to rule out SCC 1
• Follow-up biopsies: Essential in all cases that fail to respond to adequate treatment 1
• Warning signs requiring biopsy:
  • Persistent areas of hyperkeratosis
  • Erosion
  • Erythema
  • New warty or papular lesions 4

Surveillance Protocol

• Follow-up frequency: Regular long-term follow-up is essential for all patients with genital lichen sclerosus 1, 2
• Treatment compliance: Compliant treatment with topical corticosteroids may reduce cancer risk, especially in women 2

Clinical Implications

The significant association between lichen sclerosus and SCC underscores the importance of:

1. Early diagnosis and treatment of lichen sclerosus
2. Regular monitoring for malignant transformation
3. Patient education about warning signs
4. Prompt biopsy of suspicious lesions

The standardized incidence rate of vulval SCC in one lichen sclerosus cohort was 317 (95% CI 35.7-1146.2), with a cumulative risk of 14.8% compared to 0.06% in the general female population, representing a relative risk of 246.6 5. This highlights the critical importance of vigilant monitoring in these patients.