2007 RRP Focus Session

1. 2007 RRP Focus Session International RRP ISA Center Presented by Michael D. Green, MSW, LICSW (2001-7) September 15, 2007 Washington D.C.

2. Who We Are • RRP ISA’s mission is to better the lives of RRP patients and families by providing Information, Support and Advocacy (ISA) to the RRP community, physicians and researchers. • We are a non-profit 501(c)(3) organization. We are considered a charitable foundation by the IRS.

3. Information, Support and Advocacy (ISA): What We Do • Maintain a very active website and message board; issues with website to be fixed shortly. • Provide patient counseling and case-management; • Organize RRP-related conferences, Funding research into the causes and treatment of RRP. • Maintain large online survey/database (135 questions, hundreds of respondents). • See brochure for more.

4. Policy Board Up to 9 individuals

5. Scientific Advisory Panel Bettie Steinberg, PhD Tom Broker, PhDKeerti Shah, PhD Richard Schlegel, MD, PhDRobert Horlick, PhD Farrel Buchinsky, MD Robert Bastian, MDBen Heath, PhD Vincent Bonagura, MD Lisa Orloff, MD

6. A Few of Our Research Efforts ThwartHAMLET     Erbitux & p53 DrugsCidofovir Pro-drugs (HDP)    AAV2Maura Gillison-HopkinsAerosol and Ventricle Issues*AmolimigeneTA-CIN TA-HPV (Xenova) Alum Outpatient Laser Surgery (5 options) Merck/ACIP Gardasil* Artemisinin*

7. More on Gardasil • VLP-based vaccine (used viral coat proteins only) • Confers near-total immunity against HPV 6, 11, 16 & 18 (Koutsky et al., [list publication, or “verbal communication”] • Merck used reproductive tract data as main data source to generalize regarding therapeutic efficacy elsewhere in the body.

8. Merck’s Research Conclusions • Since Gardasil had no treatment effect in the reproductive tract, it was inferred that it couldn’t be effectively used in treatment anywhere. • Since Gardasil was a VLP, it was unlikely to be useful in treatment (reasoning based on assumption that VLPs aren’t useful therapeutically).

9. Dr. Ian Frazer, et al • Dr. Ian Frazer, the immunologist widely credited with inventing Gardasil, has said that VLPs can be used therapeutically. • Dr. Frazer is currently using a VLP treatment RRP vaccine in Brisbane and China. • Similar to Gardasil but without the alum adjuvant. • More on VLPs today from Richard Schlegel, MD, PhD.

10. What Does the AIDS Data Tell Us? • AIDS patients get all kinds of opportunistic HPV-infections except HPV of the respiratory tract (RRP). • Most AIDS treatment centers have never even heard of RRP. • For AIDS patients, the incidence of RRP is the same as in normal patients. • Something seems to allow AIDS patients to clear HPV in the respiratory system but not elsewhere in the body.

11. Logical Conclusions • The respiratory system functions differently from the reproductive system, at least in AIDS patients. Local immunity seems to be enough for AIDS patients to clear HPV in the respiratory system. • The assumption that reproductive data maps to the respiratory system is highly questionable, given the AIDS data.

12. Another Look at Gardasil • Perhaps low cytotoxic potential (alum issue) but we can’t say it has none. • We really don’t know. High level staff at Merck have in fact already conceded this point. • At the levels to which Gardasil boosts immunity—hundreds of times over baseline—it may have an unknown effect on the local immune system in ways we don’t yet understand.

13. Can Gardasil help RRP patients?? • Interesting Case Study of ONE • Has used cidofovir, MMR, Accutane (isotretinoin), PDT, interferon, Acyclovir, I3C, DIM and many different alternative approaches. Never had a 3-4 month period time without some re-growth. • Since February 2006, voice has been strong except for the residual effect of ~60 surgeries. Since early 2006, there has been no regrowth.

14. What was done differently? Artemisinin • Abundant literature showing that artemisinin can act as a potent cytotoxic agent against HPV-infected cells. • Dr. Schlegel’s Georgetown research with dogs. • Began using artemisinin myself in February 2006.

15. Results of Using Artemisinin • No symptoms (no hoarseness) indicative of generalized necrosis. Likely it didn’t cause kill all the HPV-infected cells. • Minimal side-effects. • Repeated use of artemisinin every 4-6 weeks. Voice sounds fine, NO regrowth.

16. Gardasil • Not satisfied with only one moving variable, in July 2006, this subject also began taking Gardasil. • Believed what I was told, i.e., that it had no therapeutic effect. • After the second injection, voice was even stronger. People who knew me remarked on it. • Placebo? Who knows? Began questioning Merck’s data. • Could Gardasil have “turned on the lights” at the local immunologic level? Could artemisinin also be helping as a cytotoxic agent? Two different variables. Who knows?

17. Pilot Study and Next Steps • Physician inquiries have been made on this from as far way as South Korea and Canada. Pulmonary use??? • I believe that a pilot study on the Gardasil/artemisinin combination is urgently needed to find out whether it works. • Multi-institutional study? Pilot study? Georgetown University is interested. Others? RFP could be vetted through Lancet, Laryngoscope and other journals.

18. Cautions • People should NOT experiment with artemisinin-like drugs, like artemether, on their own. Neurotoxicities and hearing loss have been reported in literature with artemether at high doses. • Artemisinin, however, is one of the most widely used drugs in the world for malaria; it can be used quite safely with appropriate medical supervision.

19. More Cautions • IRB is absolutely required—there have been problems with some adjunctive treatments that irresponsibly reassure patients on safety but skirt need to develop IRB. • More on website and RRP Support Forum.

20. HPV Education Initiative • RRP ISA has also tried to spread the word for high profile public education on HPV. • In our opinion, this isn’t being done very well at the present. • No excuse, now that preventative vaccine are available.

21. The Cervical Cancer/Genital Wart Obsession • HPV 6, 11 and 16 (the latter only rarely) cause RRP. • One manufacturer, however, dismissed the import of RRP when it declined to include HPV 6 & 11 in its prophylactic vaccine, saying they related to genital warts. Is the name “Cervarix” not gender-biased? • Merck shows only two HPV-caused diseases (http://www.gardasil.com). It shows cervical cancer & genital warts. On http://www.hpv.com, also by Merck, RRP in fact shows, along with cancer of the female genitalia and cervix, but a whole host of non-gender based cancers do not appear.

22. HPV: Carcinogenesis and epidemiology • Excluding non-melanoma skin cancers, 6-10% of the estimated nine million cases of cancer worldwide per year may be attributable to HPV infection. • 20-24% of all cancers in women from Latin America, Southwest Asia, and Sub-Saharan Africa are attributable to HPV. • HPV role demonstrated in cancers of: cervix, anus, rectum, penis, oropharyngeal tract, larynx and aerodigestive tract, non-melanoma skin cancers. • *The current status of development of prophylactic vaccines against human papillomavirus infections. Technical meeting report, Geneva, 16-18 February, 1999.

23. Other Cancers & HPV • rectal cancer, >50% of all anogenital cancers; 40,000 cases/yr • penile cancer, 70%; 1,400/yr • oropharyngeal cancers, 20% • larynx and aerodigestive tract, 10% • esophageal cancer 2.5/100k in US, but >200/100k in some countries Submitted courtesy of Robert Horlick, PhD (Geneva data/PowerPoint)

24. Other HPV/Cancer Data • Johns Hopkins says 25% of head and neck cancers are caused by HPV. • Almost all of it in non-smokers/non-drinkers may be. • Recent data at several institutions worldwide shows up to 50% of breast cancers. See RRP Support Forum for citations.

25. What Can Be Done to Educate People? • We have presented on this issue repeatedly in our RRP Support Forum. We testified at the CDC/ACIP hearing on Merck’s behalf in Atlanta, and we have talked many times with high level Merck staff. It isn’t that the FDA forbids education but it is possible that the big pharma lawyers think that it does. • It is clearly not sufficient to rely on the pharmaceuticals. If they are not interested in mounting a vigorous educational campaign that includes RRP and other forms of cancer besides cervical, what can we do?

26. Think Outside the Box • “Outside the Box” was RRP ISA’s subtitle to the last RRP Focus Session it facilitated in Los Angeles, 2005. • Starting today, we are inviting cooperation with the RRPF, the RRP Taskforce, the Papillomavirus Society and a host of cancer coalitions. • It is time for a broad-based educational initiative. It is time to break through the media silence on HPV.

27. RRP Support Forum and Website • More information on HPV, education, RRP treatment approaches, etc. is on the website (www.rrpwebsite.org) and our RRP Support Forum (http://rrpisa.tribe.net/). • Handouts of forum materials are in back with brochure.