RRP Foundation director Bill Stern opened the seminar with a brief list of Foundation objectives — among them, maintaining the support and information network of the website, email listserve, and family directory; collaboration with the wider scientific community, including participation in meetings and task forces; and enhancing existing databases of RRP information. The RRPF would also further develop its website and fund more research for relevant projects. Stern noted the potential difficulty of some of these tasks, due partially to the variability in presentation of RRP (i.e., spontaneous remissions and particularly aggressive cases would be hard to track for analytical purposes). He also stressed some of the challenging RRP research problems, indicating that there may be benefits to studying possible genetic factors influencing the ~ 0.005% appearance rate amongst the ~ 5% of the US population that is estimated to have HPV positive respiratory tracts.

Michael Green of the International RRP ISA Center based in Seattle, WA, also lamented the status of RRP as an orphan "backwater" disease, lacking the publicity needed for more extensive research. Citing the charitable nonprofit organization’s aims of maintaining an informative Website, empowering patients and families, improving RRP treatment and educating the general public about RRP, he declared, "[RRP] is a disease that shouldn’t be backwater because fifty million people plus in this country are infected by HPV, which is the virus that causes it." Subsequently, he offered an outline of the predictable course of an RRP patient’s diagnosis and treatment pattern — which, over the span of an adult onset patient’s life, could run up bills of up to $650,000. Green also suggested that injury of the vocal cords can often be traced to overaggressive laser therapy by doctors unaware of the dangerous potential consequences of repeated laser use, and sympathized with patients persistent in their search for experienced surgeons.

"People often value good doctors," he explained. "Who is good? Who is bad? … It’s not unusual for [patients] to travel hundreds of miles [in search of a good doctor.]"

East Virginia Medical School’s Craig Derkay, MD, University of Alabama (Birmingham)’s Brian J. Wiatrek, MD, and San Diego Children’s Hospital & Health Center’s Seth M. Pransky, MD, each offered responses to Green’s discussion of overaggressive laser therapy, presenting results of recent studies focusing on the effects of microdebrider and CO₂ laser treatment as well as the effectiveness of cidofovir. Pransky introduced the general treatment protocol practiced at San Diego Children’s, which mainly involves conservative interval debulking of papillomas to maintain an uncompromised airway and acceptable voice quality. Ultimately, the goal is to avoid a tracheostomy that could lead to changes in the cells lining the tracheal mucosa, thereby encouraging seeding of the papillomavirus.

While chemical treatment options range from interferon to DIM to ribavirin, acyclovir and HSP-E7, the predicted success of any of these measures on a patient is, at best, a "crapshoot", according to Pransky. Surgical options include removal by laser, microdebrider or steel forceps, with the majority of physicans preferring the laser and microdebrider. In operating suites, the CO₂ laser treatment is still the most widely accepted standard of papilloma management. Its popularity is drawn not only from its familiarity within the ENT community, but also from its precision (rendering it well-suited for small lesion removal), binocular visualization capabilities, and absence of incision-related bleeding during and following the procedure. Its disadvantages, however, can be significant — scarring from thermal injury or overaggressive use, airway fires, ineffectiveness on bulkier lesion masses and the risk of laser plume effects on both anesthetized patient and medical personnel are all legitimate concerns related to CO₂ laser treatment.

These factors may also be influential in the growing popularity of the microdebrider as a papilloma management strategy — an option which, according to Dr. Wiatrek, is also significantly less expensive than the laser to operate. Dr. Wiatrek emphasized the satisfaction of blinded parents of 19 patients with active RRP who collectively underwent a total of 32 procedures (18 by microdebrider, 14 with laser). Microdebrider patients reported improved voice quality, although post-operative pain levels remained the same with both devices.

While surgeons must be thoroughly familiar with the device’s applications and the appropriate choice of blade type and speed for excision procedures, the micodebrider’s effects on laryngeal tissue can be far less traumatic and better suited for peduncular papilloma regions than its laser counterpart. Some of the drawbacks associated with microdebrider treatment include sessile lesions, decreased visualization, bleeding from the blade’s incisions and the learning curve of personnel training to use the equipment.

Injections of cidofovir or Foscan-photodynamic therapy (PDT) could also run in tandem with surgical treatment. Dr. Derkay’s report of an NIH-funded PDT study at Long Island Jewish Medical Center showed that, in 18 patients, intravenously-administered Foscan followed six days later by PDT led to lessened photosensitivity and a consistent delayed response. Patients showed a trend of worsened condition in the first six months following PDT -- though in laryngeal cases, 6/10 patients were reported to be disease-free at a one-year follow-up examination, and 2/3 of tracheal papilloma cases were deemed to be markedly better.

Of fourteen adults treated with intralesional cidofovir injections in a similar study reported by Dr. Derkay, an average of six monthly injections per patient was required to achieve remission, and a favorable response was observed in all fourteen adults tracked in the study with a reasonably short follow-up period. In a separate presentation, Dr. Pransky offered further benefits of cidofovir treatment given cidofovir’s inhibition of HPV DNA polymerase and its long intracellular half-life. He cited the reduced fear of distal spread of papillomas, improved voice quality and emotional well-being, and lessened physician-induced damage. Consequently, there is discussion of a prospective multi-center pediatric RRP study, depending on the logistics of funding and cooperation by Gilead and FDA approval.

Other discussions at the seminar focused on two other perspectives of papilloma management — prevention based on genetic links, and the treatment of already-damaged vocal fold tissue. Ferrel Buchinsky, MD, of Pittsburgh’s Allegheny General Hospital emphasized that RRP is not a classic genetic disease — that is, there are few, if any, multiple occurrences in a single family according to traditional pedigree. He introduced stances on a genetic understanding of RRP, confirming that HPV6 and HPV11 are, indeed, causes of RRP — and suggesting that, perhaps, there may be other conditions that weigh heavily in the appearance or absence of the virus in individuals exposed to the virus in the vaginal delivery canal. A promising lead may be the disproportionate frequency of certain forms of HLA proteins in the RRP sample population — notable because, while everyone has these self-recognition mechanism proteins, the rabbit equivalent of human HLA proteins has been observed to be more likely to clear the infection of rabbit papilloma. For the time being, Dr. Buchinsky suggested the exploration of TDT as a method of identifying areas of genes or chromosomes linked to RRP based on gametogenesis patterns. However, for studies to be launched and continued, samples of blood and papilloma from afflicted patients and both parents (if possible) are needed, pending the approval of funding from the NIH.

On the complementary end of the treatment spectrum, Clark Rosen, MD, of the University of Pittsburgh Voice Center actively endorsed methods of post-surgical improvement of voice quality. Outlining the tracheal airflow and pressure-related physiological components of voice projection, he compared the injury to the normally elastic lamina propria and post-surgical swelling and reduced flexibility of vocal cords to " a big piece of gum on a guitar string." Dr. Rosen’s recommendation for vocal cord care centered mainly on singing therapy, treating co-morbid conditions affecting the larynx, and avoiding laser treatment in favor of precise phonomicrosurgery and measures of vocal hygiene, as well as processes of vocal fold medialization to bring damaged cords closer together via lipoinjection or thyroplasty. The collagen injections discussed by Dr. Rosen work directly on the shrunken lamina propria, while fat graft vocal fold reconstruction involves elevation of the vocal cords to incise and release scar tissue, which is replaced by the patient’s own fat as a barrier against regrowth of scar tissue and as a medium with strong vibratory properties.

"We’re not making [patients into] singers," Dr. Rosen reminded the audience, touching on the common aim of all divergent recommendations and opinions presented at the three-hour seminar. "We’re giving them a better quality of life."