High Efficacy of ALA-PDT for Mucosal Condyloma Acuminata
Tuesday, July 01, 2014
therapy (ALA-PDT) is a treatment approach for proliferative and
neoplastic skin diseases. It includes topical application of ALA
and subsequent irradiation with visible light. ALA is an endogenous
chemical substance (Figure 1), which is involved in hemoglobin
biosynthesis (Figure 2). ALA is a precursor of heme and can be
converted to protoporphyrin IX (PpIX) in tissues, which is highly
photosensitive. When exogenous ALA is administered, the rapid
proliferative tissue or tumor tissues absorb ALA more rapidly and
produce excessive amounts of PpIX. Photoreaction will be induced
upon irradiation of laser or incoherent light, generating oxygen
and free radicals, which induce necrosis and apoptosis of the cells
enriched in PpIX.
Figure 1. Chemical structure
Figure 2. The pathway of heme
Condyloma acuminata is caused by human
papilloma virus (HPV) infection. Upon occurrence in the mucosa, it
is often difficult to treat. Long-lasting high-risk HPV infection
(e.g. HPV16 and HPV18) correlates with a high incidence of cervical
cancer in women1,2 and should be treated thoroughly.
Traditional treatments for condyloma acuminata include topical
drugs, CO2 laser treatment, cryotherapy and surgical
incision. It is difficult to treat latent HPV infection, which is
an important factor for recurrence. Studies in China have suggested
that topical ALA-PDT showed a high efficacy and low recurrence for
mucosal condyloma acuminatum. This therapy can be used as a
monotherapy or in combination with laser or cryotherapy.
ALA-PDT has been approved by the China
Food and Drug Administration for treatment of condyloma acuminata.
It is more effective for mucosal lesions. The treatment procedure
involves topical application of 20% ALA solution, or gel, to
lesions. This is repeated every 30 minutes for 3 hours. The lesions
are then irradiated for 20 minutes with red light (wave length: 630
nm to 635 nm) through a cylindrical fiber; the energy fluence is
usually 100 J/cm2. Repeated treatment is performed if
necessary and the treatment interval is 1 or 2 weeks. Tu et al.
(2007) reported that 99.43% of condyloma acuminata on the urethral
orifice were cleared by ALA-PDT - similar to the result of
CO2 laser treatment (100.00%).3 The
recurrence rate was 11% in ALA-PDT treatment group and 36% in
CO2 laser treatment group (p<0.0001). In another
study, 90% of distal urethra condyloma acuminatum lesions were
cleared by one treatment. 100% clearance was achieved after two
treatments (Figure 3). Recurrence was found in only 16% patients
during the 3 months of follow-up.4
Figure 3. Clinical pictures of
patient with distal urethral condyloma acuminata.
(a) Before ALA-PDT treatment, two warts 0.3 cm in diameter were
found in the urethral meatus. (b) After one ALA-PDT treatment, the
warts had regressed.
ALA-PDT has also been successfully
used in the treatment of cervical condyloma acuminata. Wang et al.
(2012) reported that 98% of lesions were cleared after four
treatments.5 The recurrence rate was only 4% during 24
months of follow-up. Chen et al. (2011) also reported a complete
response rate of 96% while the recurrence rate was only 4% during
12 months of follow-up (Figure 4).6
Figure 4. Clinical picture of
patients with cervicalcondyloma acuminata. (a)
Before treatment, a wart of 3.5 cm x 3.0 cm was found on the
cervix. Another small wart of 1.0 cm x 0.4 cm was seen on the right
vaginal wall. (b) HPV was found by immunohistochemical stain
(arrow). (c) After one ALA-PDT treatment, both warts had regressed.
(d) After two treatments, both lesions had disappeared
Another indication for ALA-PDT is
perianal and anorectal condyloma acuminata. In a study by Lu et al.
(2012), 40 patients with perianal condyloma acuminata were treated
with topical ALA-PDT combined with curettage. All lesions had
cleared after three treatments and the recurrence rate was 15%
during 3 months' follow-up.7 In another study, Xu et al.
(2013) evaluated the efficacy of ALA-PDT for male anorectal
condyloma acuminata.8 Forty-one HIV-positive patients
were enrolled and a complete clearance was achieved in 39 patients
after three treatments. The recurrence rate was 29% at 6 months'
Zhu et al. (2012) carried out a
meta-analysis, comparing the recurrence rate of ALA-PDT and
CO2 laser combination therapy versus CO2
laser treatment alone in the treatment of condyloma acuminata.
Twenty-two articles and 2048 patients were included. Of these, 991
patients received combination therapy and 1057 patients received
CO2 laser treatment alone. The results demonstrated that
the recurrence rate was 10.3% in the combination therapy group and
42.7% in the group receiving CO2 laser treatment alone
(p<0.0001).9 Ying et al. (2013) also carried out a
meta-analysis comparing the recurrence rate between ALA-PDT
treatment and other treatments.10 The results showed
that the recurrence rate is significantly lower in ALA-PDT-treated
patients than those treated with other treatments.
In summary, ALA-PDT has a high
efficacy and safety profile for mucosal condyloma acuminata. It can
treat not only the clinical lesions but also the latent infections.
Treatment with ALA-PDT also has a low recurrence rate. Because of
aforementioned advantages, ALA-PDT is widely used in the treatment
of urethral, cervical and anorectal condyloma acuminata.
- Muñoz N, Bosch FX, Castellsagué X, et al. Against which human
papillomavirus types shall we vaccinate and screen? The
international perspective. Int J Cancer
- Cogliano V, Baan R, Straif K, et al. Carcinogenicity of human
papillomaviruses. Lancet Oncol 2005;6:204.
- Tu P, Zheng HY, Gu H, et al. Topical 5-aminolevulinic acid
photodynamic therapy for the treatment of condyloma acuminatum: a
multicentre, randomized, CO2 laser-controlled trial.
Chin J Dermatol 2007;40:67-70.[Chinese]
- Sun Y, Ma YP, Wu Y, et al. Topical photodynamic therapy with
5-aminolaevulinic acid for condylomata acuminata on the distal
urethra. Clin Exp Dermatol 2012;37:302-3.
- Wang HW, Zhang LL, Miao F, et al. Treatment of HPV
infection-associated cervical condylomata acuminata with
5-aminolevulinic acid-mediated photodynamic therapy. Photochem
- Chen MK, Luo DQ, Zhou H, et al. 5-aminolevulinic acid-mediated
photodynamic therapy on cervical condylomata acuminata.
Photomed Laser Surg 2011;29:339-43.
- Lu YG, Yang YD, Wu JJ, et al. Treatment of perianal condyloma
acuminate with topical ALA-PDT combined with curettage: outcome and
safety. Photomed Laser Surg 2012;30:186-90.
- Xu J, Xiang L, Chen J, et al. The combination treatment using
CO2 laser and photodynamic therapy for HIV seropositive
men with intraanal warts. Photodiagnosis Photodyn Ther
- Zhu X, Chen H, Cai L, et al. Decrease recurrence rate of
condylomata acuminata by photodynamic therapy combined with
CO2 laser in mainland China: a meta-analysis.
- Ying Z, Li X, Dang H. 5-aminolevulinic acid-based photodynamic
therapy for the treatment of condylomata acuminata in Chinese
patients: a meta-analysis. Photodermatol Photoimmunol