Lichen sclerosus and Lichen planus and risk for malignancy Maija Jakobsson MD, Ph.D, Consultant Helsinki University Hospital Finland

Employer Helsinki University Hospital Conflict of interest Employer Helsinki University Hospital No conflict of interest regarding the contents of this presentation

Risk factors for vulvar cancer Case reports, LS/ LP Contents ISSDV terminology Risk factors for vulvar cancer Case reports, LS/ LP Differentiated VIN- dVIN Finnish register study Conclusion

Two pathways for vulvar cancer High risk HPV negative LS or LP dVIN SCC High risk HPV positive LSIL HSIL SCC 30%? 3- 9%

LSIL of the vulva HSIL of the vulva DVIN 1986 ISSVD 2003 WHO 2012 LAST ISSVD 2015 WHO 2014 Vulvar Intraepithelial Neoplasia (VIN) Intraepithelial Lesion Vulvar Squamous Intraepithelial Lesion (SIL) Squamous type (with or whitout HPV change) Flat condyloma or HPV effect Low grade SIL-LSIL (VIN 1) LSIL of the vulva (vulvar LSIL, flat condyloma, or HPV effect) - VIN 1 - VIN 2 - VIN 3 (Formely Squamous cell CIS, Bowen’s disease, Erytroplasia of Queyrat, CIS simplex) VIN usual type -VIN warty type -VIN basaloid type -VIN mixed type (warty / basaloid) High grade SIL- HSIL (VIN 2, VIN 3) HSIL of the vulva Differentiated VIN VIN, differentiated type DVIN Non-Squamous type Paget’s Disease Melanoma in situ Modified from Bornstein

What are the main risk factors for vulvar cancer ?

Risk factors for vulvar cancer 1.3 million women aged 49-65 898 vulvar cancers (ICD code C51) Cox regression models Risk factors: Prior CIN3 (RR 2.68, CI 1.71- 4.18) 2 % of all vulvar cancers Obesity (RR 1.71, CI 1.44-2.04) Menopause <50 yrs ( RR 1.52, CI 1.22-1.89) Coffey et al 2016

A clinical study of 23 cases of female anogenital carcinoma age 43-83 all had vulvar symtoms prior to diagnosis 1-30 years: 8 prior diagnosis of LS/ LP 12 clinical signs of LS 3 of LP 5 some canges both LS and LP 2 VIN3 1 no vulvar skin disease Derrik 2000

How big is the risk of cancer with LS? 253 women, 6 developed cancer (2.4%) (66 months) Cooper 2004 211 women with 3 (1.4%) SCC (1 yrs 8 months) Carli 1995 107 women, 7 had co-excisting SCC 1/ 92 (1.0 %) developed SCC in the follow-up Hart 1975 32 symtomatic LS women, 9 % developed VIN lesions, 21 % invasive SCC (mean 4 years) Carlson 1998

Lichen planus and vulvar cancer? Some case reports Ramos-e Siva 2000 38 patients with LP planus accociated vulvar cancer All were HPV-negative Regauer 2014

Cumulative incidence of SCC among LS patients Maaike 2016

LS OR DVIN? LS without progression (n=61) Revision of ‘Lichen Sclerosus (et atrophicus)’ and ‘vulvar dystrophy’ by two expert pathologists Data between 1988-2008 Minimum follow-up of 10 years LS without progression (n=61) in 58 cases (95%), diagnosis was unchanged LS with progression to SCC (n=60) in 25 cases (42%) were reclassified to dVIN time to progression for dVIN 28 months for LS 84 months (p=0.001) van de Nieuwenhof 2011

Does compliance of the treatment decrease the risk of SCC? Prospective, longitudinal cohort study in 507 women with biopsy confirmed LS Follow-up from 2008 to 2014 Age 55.4 (range 18-86) Duration of follow up 4.7 yrs (range 2.0-6.8) Induvidualised regiments for corticosteroids defined by degree of hyperkeratosis 150 patients (29.6%) did not carry out adviced treatment (= partially compliant) Lee. JAMA Dermatol.2015

Dergree of keratinisation

Outcome Compliant (n=357) Partially compliant (n=150) P value SCC or VIN SCC 7 (4.7%) 3 (2.0%) <0.001 Progression of adhesions or scaring 12 (3.4%) 60 (40.0%) Symptom resolution 333 (93.3%) 87 (58.0%) Improved in dyspareunia 194 (93.7%) 68 (65.4%) Adverse effects Corticosteroid dermatitis 8 (2.2%) 6(4.0%) 0.37 Atrophy 4 (1.1%) 0.43