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.