Role of bevacizumab in juvenile onset recurrent respiratory papillomatosis

Juvenile-onset recurrent respiratory papillomatosis is a childhood disease notorious for its propensity for recurrence. The children are put through the trauma of repeated surgical procedures affecting the physical and emotional quality of life. Many adjuvant therapies are tried to prevent recurrence of the disease after surgical treatment. Bevacizumab is a monoclonal antibody against vascular endothelial growth factor, which has been recently added to the armamentarium of adjuvant therapy. The present study tries to review the various studies in English literature evaluating the role of bevacizumab in Juvenile-onset recurrent respiratory papillomatosis. Correspondence to: Dr. Abdul Wadood Mohammed, Department of ENT, College of Medicine, King Faisal University, Al Ahsa, Kingdom of Saudi Arabia, E-mail: wadood_abd@yahoo.co.in , Wadood83@gmail.com


Introduction
Juvenile-onset recurrent respiratory papillomatosis (JORRP) is a chronic infection of viral etiology affecting the upper aerodigestive tract characterized by proliferative lesions over the mucosa. It is due to human papilloma infections acquired from the birth canal of the mother. Even though it has more predilections for the larynx, it can present at any site in the respiratory tract [1,2]. The disease is usually benign, but often has a high chance of recurrence, which is usually attributed to incomplete surgical removal of the causative virus. Malignant transformation has been reported to occur in long-standing cases [3].
To prevent recurrence adjuvant therapy is advised after definitive surgical treatment. Many agents are suggested for as adjuvant therapy including cidofovir, SGN-00101, interferon, indole-3-carbinole, cis-retinoic acid, mumps vaccine, HspE7, photodynamic therapy etc. There has been evidence that vascular endothelial growth factor receptor plays an important role in the development of recurrent respiratory papillomatosis. Bevacizumab is a recombinant monoclonal immunoglobulin antibody, which inhibits the biologic activity of human vascular endothelial growth factor there by preventing receptor activation. The present study tries to review the English literature regarding the role of bevacizumab in JORRP.

Methodology
A comprehensive literature review was done in PubMed using the medical terms juvenile onset recurrent respiratory papillomatosis AND Bevacizumab. That article which was general discussion, non-English language and off-topic were removed. The articles, which dealt with the same topic in the references of these articles, were included in the study (Figure 1).

Results
The initial search in PubMed using medical terms juvenile onset recurrent respiratory papillomatosis and Bevacizumab revealed 10 articles. After initial scrutiny, 4 articles were included in the study after excluding one german article, 3 off topic articles, and 2 general discussions. One article of the similar topic was included in the study for the references. In the end, there were 5 articles for study (Table 1).

Discussion
Juvenile-onset recurrent respiratory papillomatosis is benign, but troublesome disease due to its propensity for recurrence and need for multiple surgical procedures. To reduce recurrences the patient is started on adjuvant therapy. Many agents have been tried for adjuvant therapy. Bevacizumab is a monoclonal antibody against vascular endothelial growth factor (VEGF). Studies have shown strong expression of VEGF-A mRNA was noted in the squamous epithelium of papillomas and VEGFR-1 and VEGFR-2 were noted in the endothelial cells of the underlying vessels [4].
In a Prospective observational study by Mohr et al. [5], immediate and sustained response was seen after systemically administering bevacizumab was observed in five patients with progressive JORRP who underwent multiple local procedures. Another significant observation was that 4 out of 5 patients did not require any further surgical intervention. One patient underwent laryngectomy due to malignant transformation. They recorded the response of the lesion to treatment during the administration of the drug and those patients who showed relapse on discontinuation of the drug showed a response on retreatment. Sidell et al. [6] demonstrated a median 58% improvement in 5 patients who underwent sub epithelial injections of bevacizumab along with KTP LASER ablation. Another study by Zeitel et al. [7] combining sub lesional bevacizumab with KTP laser found that there was a significant response to the disease. Out of 20 patients who received 4 injections, 3 had no discernible disease, 16 patients had a partial response and 1 patient had increased disease. 7 of the patients did not require any further laser coagulation. In a prospective case series by Roger et al.

Conclusion
The review concludes that there is ample evidence to suggest that bevacizumab is a good agent for adjuvant therapy of JORRP. It is either effective when used systemically or intralesionally alone or along with microdebrider or KTP Laser. However, the adequate duration of treatment has to be evaluated as the disease relapsed when the drug was stopped in some studies. More studies are needed comparing the efficacy of different agents used in adjuvant therapy.  Copyright: ©2016 Mohammed AW. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.