Therapeutic options and malignancy risk
Embracing the theory of immunosuppression as a player in the carcinogenesis of vulvar LP, the therapeutic choices for this disease can and should be questioned. Some second line drugs such as calcineurin inhibitors (i.e. tacrolimus and pimecrolimus), which are topical alternatives to corticosteroids in the treatment of vulvar LP, have directly been associated with reactivation of HPV in response to local immunosuppression.18 Its use has also been associated to VSCC, with 2 cases described in vulvar LS and one in penile LS where a correlation between application site and malignancy occurrence was assumed.19,20
Aside from these concerns, it is acknowledged that corticosteroids have an anti-inflammatory effect that reduces local disease activity and the transformation risk associated, via an HPV-independent pathway.5 Also, their use has recently been identified as an important resource to reduce the recurrence rate of VSCC and dVIN in patients with LS.21 For this reason, the hypothesis that relates immunosuppression induced by corticosteroids with the risk of HPV related premalignant and malignant lesions, should not sustain an undertreatment policy for vulvar LP, but other drugs like calcineurin inhibitors should only be used as second line therapy and for short periods.19 Another important point in favor of its use is that the risk of HPV-dependent lesions in the territory of vulvar LP seems low.
We believe that use of topical and systemic corticosteroids and other immune modulators should still be the gold standard for these patients. The long-term benefits, both in terms of symptoms control and in reducing the risk of HPV-negative malignancies should support therapeutic decisions. However, the treatment of vulvar LP after a diagnosis of HSIL is challenging and one should consider reducing the dose and frequency of topical corticosteroid used for disease control and choose second line treatments other than calcineurin inhibitors (i.e. retinoids) when necessary.