More Clinical Updates

Gonorrhea and syphilis are common sexually transmitted diseases (STDs) that share many characteristics.

Read more

Oral lichen planus (OLP) is as common as psoriasis and affects approximately 1-2% of the population. The disease develops in women more than twice as often as in men and most commonly occurs in the fifth to sixth decade of life, although the disease can sometimes affect children.

Read more

Recalcitrant cutaneous lupus erythematosus (CLE) causes patients considerable discomfort and often leads to disfigurement. Although the majority of CLE responds to the combination of sun protection, local glucocorticoids, and antimalarials, some cases require more aggressive therapy.

Read more

Solar ultraviolet (UV) radiation is the most important environmental factor involved in the pathogenesis of skin cancers.

Read more

Clinical Updates

Jianzhong Zhang

High Efficacy of ALA-PDT for Mucosal Condyloma Acuminata

Jianzhong Zhang

Tuesday, July 01, 2014

5-aminolevulinic acid-photodynamic 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.

 

ALA

Figure 1. Chemical structure of ALA

 

Heme

Figure 2. The pathway of heme biosynthesis

 

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

 

Urethral condyloma acuminata

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

 

Cervical condyloma acuminata

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 completely.

 

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' follow-up.

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. 

 

References

  1. Muñoz N, Bosch FX, Castellsagué X, et al. Against which human papillomavirus types shall we vaccinate and screen? The international perspective. Int J Cancer 2004;111:278-85.
  2. Cogliano V, Baan R, Straif K, et al. Carcinogenicity of human papillomaviruses. Lancet Oncol 2005;6:204.
  3. 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]
  4. 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.
  5. Wang HW, Zhang LL, Miao F, et al. Treatment of HPV infection-associated cervical condylomata acuminata with 5-aminolevulinic acid-mediated photodynamic therapy. Photochem Photobiol 2012;88:565-9.
  6. 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.
  7. 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.
  8. 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 2013;10:186-93.
  9. 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. Dermatology 2012;225:364-70.
  10. 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 Photomed 2013;29:149-59.

 

 

Back