RRP ISA Survey Results

    (Important Disclaimer)


    2004 (New York City)

    RRP Focus Session

    The International RRP ISA Center and RRPF co-sponsored a RRP Focus Session on September 18, 2004 in conjunction with the American Academy of Otolaryngology meeting in New York City. Generous support for this meeting was provided by Medtronic Corporation and Stressgen Biotechnologies .

    By RRP ISA's count, there were approximately 80 attendees, including about 60 RRP patients/family members and about 20 RRP doctors/ researchers.

    Bill Stern and Michael Green provided some introductory remarks and discussed some organizational objectives.  They were followed by presentations from Thomas Mingot, Dr. Bettie Steinberg , Dr. Mark Shikowitz , Dr. Graciela Andrei, Dr. Nigel Pashley, Dr. Alan Shaw, Dr. Robert Bastian and Dr. Tom Broker.  Due to the severe impact of Hurricane Ivan in the Birmingham, Alabama area, Dr. Brian Wiatrak was unable to attend, but did email his presentation, which Dr. Broker was able to cover in part during his talk. After the presentations there was time for some interesting follow-up discussion.

    Readers are encouraged to go directly to the following PowerPoint presentations that were made available for distribution. Where these PowerPoint presentations were unavailable, we used the RRPF website summary which, in the interests of avoiding duplicated effort, we were given permission to copy.

    Click on the hyperlink to go to the PowerPoint presentation:

    (1) RRP Priorities, Statistics and Perspectives
    Bill Stern , RRP Foundation

    (2) International RRP ISA Center
    Michael Green, International RRP ISA Center

    (3) Comments from Stressgen Biotechnologies Thomas Mingot

    Stressgen provided an update on their immunotherapeutic treatment for RRP, HspE7.  It is currently under consideration by the FDA for a Phase III clinical trial involving ~150 RRP patients.  It is hoped that the FDA approval will come before the end of the year.

    (4) Immune Responses in RRP
    Bettie Steinberg , PhD
    Long Island Jewish Med. Ctr.  Dept. of Otolaryngology

    (5) Recurrent Respiratory Papillomatosis (RRP): Celebrex and COX-2 Inhibition
    Mark Shikowitz , MD
    Long Island Jewish Dept. of Otolaryngology

    (6) Cidofovir Mechanisms in Suppressing Papilloma - Graciela Andrei, PhD, Rega Institute for Medical Research , Belgium

    Anti-viral activity spectrum of cidofovir Papovaviridae

    Murine polyomavirus
    Human polyomavirus
    Rabbit papillomavirus
    Human papillomavirus es (several types)

    Some examples of treating laryngeal papillomas with cidofovir

    1) Cidofovir was administered by local injection (directly into the tumor) at 1.25 mg/kg at weekly intervals. Complete regression of the tumor was achieved after 7 injections
    2) Cidofovir (2.5 mg/ml) was injected directly into the tumor. Complete regression of the tumor was achieved after 15 injections over 9 months.
    3) Cidofovir (2.5 mg/ml) was injected into the tumor. Complete regression of the tumor was achieved after 15 injections every 2 to 3 weeks.

    Mechanisms of anti-viral activity associated with cidofovir

    Anti-proliferative effect on papillomavirus cells
    The mechanism of cell death following cidofovir treatment appeared to be apoptosis, which was associated with accumulation of cells in the S-phase, increase in p53 and p21 levels and downregulation of the viral oncoproteins E6 and E7.

    Further studies are ongoing to determine the selective mechanism of action of Cidofovir and other potential antiviral agents, such as PMEG, against HPV.

    (7) Mumps and MMR Vaccine for RRP - the Saga Continues  
    Nigel Pashley, MD, Children's Ear Head & Neck, Denver

    Dr. Pashley said he first started using mumps in 1980, presented data at ASPO (American Society of  Pediatric Otolaryngology) in May 2001.  By January 2002  no mumps vaccine was available, so he started using MMR in  January 2002. (Mumps is now available again.)

    Dr. Pashley states, that to his knowledge, using a vaccine to actually treat a different disease has not been investigated before his study. If this treatment approach were to be proven effective, he believes that there may be other virally associated diseases which could be treated in this manner.

    Mumps/MMR protocol

    Excise papilloma with CO2 laser, 2-5 Watts
    Inject MMR/Mumps vaccine into base of where papilloma were excised
    ~ 1/2 ampule given as sub-cutaneous immunization

    Table of results treating RRP patients with MMR:
    Patient sample size = 34
    24 adults (3F/ 21M),  10 children (3F/ 7 M)
    Follow up = 6mo- 2yr 6 mo.

    severity score
    MMR (amount)
      before after
    21/24 = 87.5%
    Adults 19-28 1-6
    Child 18-24 2-6
    8/10   = 80%

    (Where remission is defined as two typical surgical intervals in which the RRP patient is found to be disease free.)

    Remission group includes 6 mumps alone failures who became MMR successes and includes 8 for whom a single MMR treatment resulted in remission.

    Mumps alone gave a 75% remission with about the same follow up, based on treating 46 RRP patients.

    (Complete results from using mumps alone is reported in Archives of Otolaryngology July 2002 pp 783-786 vol 128 and is  available on line at www.archoto.com ).

    Dr. Pashley notes that it is important to remember that this is an ongoing series and that this is the remission rate at the time of the survey,  It may improve with longer treatment and follow up.  Also there are no non-responders, i.e. everyone gets some beneficial lengthening in their intervals and less recurrence (Dr. Pashley believes that these patients then go into remission after the study period)

    (RRP ISA editorial note: The data reported by Dr. Pashley appears to be at significant variance with the data reported by patients in our online survey and also in the RRPF survey. Also, see Bettie Steinberg's article on safety issues relating to MMR and other treatments. Also see remarks on Dr. Pashley's approach in Treatment Strategies>MMR and in the 2007 RRP Focus Session Report.)

    (8) Merck's HPV Vaccine Research
    Alan Shaw, PhD, Merck Research Labs

    (9) Two Methods of Cidofovir Injection in the Office Procedure Room
    Robert Bastian, MD, Bastian Voice Institute, Downers Grove , IL

    (10) HPV-6 and HPV-11 in RRP: Correlation of disease severity with HPV-11; Plans for future Workshops and public education
    Thomas Broker, PhD, Univ. of Alabama in Birmingham , Biochemistry and Molecular Genetics

    (11) Quality of Life Issues Effecting Pediatric RRP Patients
    Brian Wiatrak, MD, FACS, FAAP, Chief, Pediatric Otolaryngology The Children's Hosptial of Alabama

    (Note: This talk was not presented because the impact of hurricane Ivan prevented Dr. Wiatrak from leaving Birmingham in time for our meeting.  The summary of the presentation is based exclusively on a PowerPoint presentation that Dr. Wiatrak email us.)

    The main focus of this study is to define what quality of life (QOL) is, determine whether it is effected in our RRP patients and how much.

    Definitions of QOL

    Health - the condition of being sound in body, mind or spirit; freedom from disease or pain.

    • The degree to which a person enjoys the important possibilities of his or her life.
    • Factors - health, function, future potential, socioeconomic status

    Can it be measured?   YES

    Use of PedsQL to Assess Health-Related Quality of Life in Children with RRP

    • Wiatrak, Lindmann et al   (Funded by RRP foundation)
    • QOL instrument designed for people with chronic illness
    • 23 questions
    • 4 subscales (physical, emotional, social, school functioning)
    • Parent proxy reporting for children 4yo and under
    • Parent AND child reporting for older pts.
    • Results compared to validated ?normal? healthy children AND compared to
      children with other chronic illnesses i.e. cancer, renal, CF etc..

    Results  (27 patients ages 2-18)

    RRP has a significant effect on QOL
    Compared to healthy children:

    • Self reporting (age 5-18)
      • Significant (P=<.05) worse QOL for total score, psychosocial aspects, social functioning, school fx)
    • Parent reporting
      • Very significant (P=<0.0001) in ALL scales

    Parents seem to perceive things worse than their self reporting children


    • Compared to Children with OTHER illnesses
      • Self reporting (age 5-18)
        • Trend towards significance in all scales
        • Significance (P=<0.05) in school functioning
      • Parental reporting
        • Trend toward significance in all scales
        • Significance in psychosocial (P=<.05) and school functioning (P=<0.0001)

    Significance of study

    Demonstrates in a ?more? objective way the effects of RRP on a patient's quality of life

    Objective data may be used to justify more extensive RRP research which is still considered an orphan disease.

    National based study needed utilizing field tested and validated RRP QOL instrument.