Recurrent Respiratory Papillomatosis: Much Has Been Done, but a Long Road Lies Ahead

Recurrent respiratory papillomatosis (RRP) remains a devastating disease for pediatric patients. Each time we diagnose a new case of RRP we are reminded of our limitations in battling a disease that has no known cure, that has an unpredictable course, and that carries a risk of morbidity. Answering probing questions from family members about disease transmission requires sensitivity, as the knowledge that it is a vertically transmitted disease often evokes much guilt in parents.

The lack of a cure for this disease cannot be attributed to lack of research efforts. An infectious etiology for RRP was first proven in 1923 when Ullman injected homogenized papillomata from a child’s larynx into his own forearm and developed papillomatous lesions at the site three months later. Clearly, Dr. Ullman was operating prior to the creation of Institutional Review Boards! Numerous investigators have since sought to find a cure for this virally transmitted disease. Countless treatment modalities have been proposed based on promising preliminary results, only to find that the purported benefit was more likely a reflection of disease variability than efficacy of the drug. I recall the wisdom of Professor Bruce Benjamin, who told me during my fellowship that cures for RRP come and go like passing trends. His wisdom has prevailed.

Vaccines: A Great Leap Forward

The FDA approval of Gardasil in June of this year is the most exciting news for otolaryngologists who treat patients with RRP. This quadrivalent vaccine combines empty virus-like particles with the L1 major capsid protein of HPV-6, -11, -16, and 18 to induce a robust host-antibody response. The Phase II and Phase III trials have demonstrated remarkable safety and efficacy in preventing HPV-related cervical dysplasia and carcinoima in situ from the viral subtypes of interest. While the impetus for creating the vaccine has been to prevent anogenital HPV-related disease, the potential for preventing RRP, which is often considered an orphan disease, is clearly our windfall.

The cost of $360 for the three vaccines that are administered over a six-month period is trivial compared with the anticipated reduction in health care costs allocated to manage HPV-related disease. More than $100 million is spent annually to treat patients with RRP in the United States. This amount is small in comparison to the $1 billion allocated to treat HPV cervical dysplasia, cervical carcinoma, and anogenital warts. Americans unable to afford vaccine therapy can receive it through the Vaccines for Children Program, sponsored by the Centers for Disease Control and Prevention (CDC), or through an adult patient assistance program offered by Merck. The Bill and Melinda Gates Foundation announced in June its plan to give $27.7 million to fund research on how best to introduce the new vaccine to third world countries where HPV causes 25% of all cancers in women.

Use of the vaccine will not obviate the need for PAP smears, as other HPV viral subtypes not covered by the vaccine can still cause premalignant and malignant changes in the cervix.