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ELSEVIER

Epidermodysplasia
Verruciformis.
Immunological
and
Nonimmunological
Surveillance
Mechanisms: Role in
Tumor Progression
SLAWOMIR
MAJEWSKI,
STEFANIA
JABLONSKA,
GERARD ORTH, VMD

MD
MD

pidermodysplasia verruciformis (EV) is a rare genodermatosis that is found to be associated in


about half of the patients with cutaneous cancers.i Great interest in this rare disease, first described
by Lewandowsky and Lutz in 1922,2was aroused after
its association with human papillomavirus (HPV) was
discovered. 3,4 Thus, EV is essentially a genetically determined, life-long HPV infection of the skin however,
HPVs specific for EV (EV I-IPVs) are harmless for the
general population, and therefore this infection can not
be transmitted to the normal individual.
The persistence of EV I-IPV infection is due to the
inability of the patients immune system to reject the
cutaneous lesions, which is due to some still unknown
immunogenetic defect. Since cancers develop in the cutaneous lesions associated with EV HPVs, this genetic
disorder represents the first model of human viral cutaneous oncogenesis.5
EV HPVs were first characterized in 1978;3and today
over 20 cloned EV HPVs are known, and several further
are being characterized. An important finding was detection of EV HPVs or EV-related HPVs in cutaneous
cancers of immunosuppressed population that provided evidence for the role of defective immune surveillance in the development of EV lesions and in the
progression of EV HPV-associated cancers.6-9

Epidemiology
Epidermodysplasia verruciformis is distributed worldwide; it has been found on different continents and in
various races.l-12 In all of the patients, the inducing EV
HPVs were similar. The benign lesions are associated
with diverse EV HPVs; while malignant tumors are preFvom the Departmenf
of Dermatology, Warsaw
Klinika Dermatologiczna,
Warsaw, Poland.
Address corresporzdence
to Dr. Slawomir Majewski,
logiczna, Ul. Kozykowa
82A, 02-008 Warsaw, Poland.

0 1997 by Elseuier Science Inc.


655 Aoemce of the Americas, New York,

School of Medicine,
Klinika

Dermafo-

dominantly associated with HPV types 5 and 8, much


less frequently with HPV types 14, 17, 20, and 47, although HPV type 47 was reported to have a higher
oncogenic potential than the other three.i
EV HPVs do not infect immunocompetent persons;
however, EV HPVs were reported in the immunosuppressed population within the lesions having clinical
and histological features of EV.13-i6 Similarly EV lesions
were described in patients infected with human immunodeficiency virus (HIV).i7,i8 In immunosuppressed
patients, with the preserved host-cell restriction of the
EV HPV genome, infection with EV HPVs has no typical morphology and is rather transitory. In these individuals EV HPVs may be also codetected in plane warts
induced by HPV types 3, 10, and 28 that have all the
characteristics of warts in the general population.9,20
EV HPV infection may be facilitated by HPV type 3 or
related HPV types that provide trans viral proteins El
and E2, enabling persistence of episomal viral DNA.21
Thus, immunosuppressed population may be regarded
as a reservoir of overt or latent EV HPVs, including
potentially oncogenic types; therefore this population
presents a high risk of cancer development.
Because heavy immunosuppression is associated
with all types of HPVs, among others EV HPVs, it is
conceivable that EV HPVs are widely distributed and
are present in latent form in the general population,
producing EV lesions only by activation in consequence
of breakdown of immunity, mainly in allograft recipients. The risk of developing cancers depends on the
duration of immunosuppression, the immunosuppressive regimen, and the age of the patients. An overall
50-fold excess risk for developing squamous cell carcinoma (SCC) and 5-fold excess risk for developing basal
cell carcinoma (BCC) was found by a mean interval of
3.5 years from organ transplantation to skin cancers.22
Others reported the cumulative risk for cancer after 3
years of graft life as 18%.23 At 9 years posttransplant,
warts were found in 89% of patients and SCC in 40%.24
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