Hi all --

It's been a while since I updated the HPV (human papilloma virus) vaccine trial Barry's in -- he had his last phoresis a week ago (that's where they harvest white bood cells for the post-inoculation immune response tests) -- a two-hour procedure that the Hopkins people try to make as pleasant as possible but it is hard to make pushing all your blood through a machine and then putting it back in really nice! The movies on a large-screen TV and the body-sized heating pad help.

Barry's now had three of four injections with the DNA vaccine, abslutely no reaction which appears to be typical, although we noticed he has a slight touch of acne on his forehead and back. We met with Dr. Gillison (the principal investigator) last Friday and she noted this, but not sure if it's due to some immune response or just coincidental.

There wll be one more injection of the vaccine and a collection of cells (not a phoresis, though) in about two months. Then the next cohort will start, with the next-highest dose of the vaccine. Dr Gillison said there are only two spots open in the trial now -- if anyone is interested, it's for patients who have had an HPV+ SCC of the oropharynx and who are at least 4 months post-treatment and considered cancer-free. Hopkins will test the tumor for HPV if it has not been done already. There is at least one other member of this forum in the trial.

The analysis of all the results will wait until the whole trial is completed. A similar trial (same vaccine) with cervical cancer patients is being analysed, preliminary results indicate that the vaccine does boost the immune response to the virus and thus could help "clear" the virus from a patient.

This is the crux of the issue: What IS known is that patients who develop HPV-induced cancers somehow have not "shed" the virus like the majority of us (80% of population is infected at some time in their lives but in only a few does the virus stick around and -- years later -- cause cancer). No one knows why this happens, the same individual may have a perfectly good immune response against influenza or other disease virus.

Barry asked Dr. Gillison this question and she said it was a good one, with no clear answer: If you have an HPV+ cancer (cervical, oral) and you are successfully treated, is the virus still present? There is some evidence from cervical cancer that the virus may become inactive (latent) and then, come back. Dr. G. described an ongoing study in which a pathologist is looking -- slice by tiny slice -- at cervical tissue from women who were successfully treated for cancer in the past, no recurrence, but who now (for another reason) are having a hysterectomy. The tissue will be tested to see if the HPV is still present in the cervix, although latent (inactive).

The goal of this DNA vaccine is to induce an immune response against the virus by boosting T-cell recognition -- the ultimate goal being to rid the patient of the virus and thus the chance of the cancer reappearing. In fact, in animal trials the vaccine alone was able to cause HPV tumors to recede.

Once the Phase I of the trial is over, if the vaccine does cause an immune boost, then the next step might be to test against patients with active HPV cancer (probably as an adjunct treatment).

Dr. Gillison confirmed her earlier statements about rate of recurrence of HPV+ cancers (no more than 15%) and that most recur in first two years (which is the norm for HNC). The recurrence is usually in the lymph nodes and whether there was a ND or not doesn't seem to change that much. Barry is 18 months out now so keeping his fingers crossed!

The results of this Phase I trial will start to be analyzed after the end of the fourth (highest dose) cohort so still some time off.

Gail

Gail,

What's involved time wise? Do you think I might be a candidate? I was never tested for HPV but I was a very casual cig smoker and had quit over 30 years before Dx and I was a casual drinker.

Hi David,

Jack is the other member of the forum involved in the clinical trial, thanks to Gail's information in her posts and emails. He is in the same dose cohort as Barry and has also had no reaction to the first 2 doses, with the 3rd one scheduled for next week. Since we are out of towners as you would be, Hopkins is working with us to minimize the number of times we need to go there in person.

The first step was to have the tumor slides sent to Hopkins for testing to see if they were positive for the HPV 16 virus. I followed the link for Hopkins clinical trials that Gail gave us and called the research nurse to find out how to do that. She emailed me the forms to take to our local hospital and they sent the slides to Hopkins following the protocol outlines. That process took about 2 months, but once the tumor came back positive things moved very quickly for us.

We arranged a consult with Dr. Gillison Oct 14th after obtaining and sending Jack's entire medical records from the surgeon, the RO, the MO, as well as his biopsy reports and PET/CT scan results. Dr. Gillison reviewed the records, examined Jack, discussed the clinical protocol and study particulars and based on all that accepted him as a patient. He had blood work and a chest X Ray at Hopkins during that visit and would have received the flu shot and tetanus if he hadn't already had them.

Once we signed the consent the research nurse set up the first phoresis that Gail is referring to - for Jack that was done on Nov 1st as well as minor skin testing. Jack had his first vaccine on Nov 29th and the second on Dec 14th. We are going back on Dec 27th for the 3rd. The next visit is his second phoresis scheduled for Jan 18th, followed by a check up on Jan 29th. There's a lot of flexibility on the check up date, we're just trying to accomodate our rescheduled anniversary trip. After that he doesn't have to go back until Mar 21st for the booster shot of the vaccine and then I think it's 3-6 months going back down there. The study is over a 2 year period.

Because we are out of towners, we were allowed to go to our local doctor-with the Hopkins study form - to be checked 48 hours after the skin testing and the first injection, as well as the "off" weeks in between injections to examine Jack for any allergic reactions. That has been a big help because he can run over to the local doctor for an in and out visit a lot more easily than going back to Hopkins. It's the only reason we're able to participate from a distance and handle 48 hour and weekly follow up.

So yes there's a fair amount of time involved in doing this but they will work with you. Blood work needs to be done at Hopkins and that is taken care of the morning of our visits. Since we usually come in the night before we take advantage of the Hopkins rates at nearby hotels, and they have a travel bureau that works with out of towners.

Hope this helps,
Regards JoAnne
PS...and the crab cakes are fabulous

Thank you for the update, Gail. I have been very interested in all your posts concerning this trial.
When Mike was first diagnosed in July, I brought up the subject of the HPV connection with each doctor. I'll never forget how they looked at me like I was from Mars. Then, each one gave some extremely lame response.
I didn't know if Mike had HPV, I thought they might want to test for it. I knew it did not change anything, he still had SCC BOT, his treatment would be the same.
I also knew from reading on the National Cancer Institute web site that increasing numbers of younger, non or light smokers and drinkers where getting Oropharynx cancer. And they were reacting significantly better to standard treatment protocol.
Your in depth reporting on the trial helps satisfy my curiosity on the HPV connection. Which Mike's doctors failed to acknowledge.
Thank you Barry and Gail for being participants in the study and for the well written reports. Keep us posted!
Ginny
(Mike's wife)

Thanks Joanne,

I'll wait for the info you spoke of from Gail. I'm willing to see if mine was caused by HPV and take it one step at a time.

Hi Gail,

I would like to thank you for taking the time to post your updates. I have been following Barry's trip through this study with great interest. It's amazing how many of my colleagues had no idea about the connection of HPV with oral cancer. Because of your postings, I am able to educate them.

And Joanne, I'm happy to see that Jack is part of the study, too and I commend all of the paticipants who will more than likely help to have a positive impact on so many people's lives.

I have been participating in an ongoing health study run by Harvard since I was a student in dental school in the late 60's. Until I got my cancer, my questionaires were pretty routine as I was a healthy guy till then.

Jerry

Actually, it is amazing how many doctors (even at Hopkins, the "hotbed," so to speak, of HPV-HNC research). Barry went to see a neurologist there to have his benign essential tremor checked out, as he had not seen a specialist about it for about 3 years. Had it worsened over time and if so, should he up his meds? When he told the doctor that he had been treated at Kimmel for throat cancer the first thing the doctor asked was, "oh, were you a smoker?" -- Needless to say, we both enlightened him !

The answer on the tremor was it had not progressed. He also asked what chemo drug Barry had. We told him that Barry's chemo drug (carboplatin) rarely caused peripheral neuropathy, nevertheless he also tested Barry for that -- compared feeling in his feet to elsewhere, etc.-- and found no problem.

Now, David -- JoAnne's answer pretty much sums up what you have to do. I would start by googling Dr. Gillison and getting her contact email, and start from there. There IS a lot of time involved, we are up and back every week or so but as JoAnne noted they will work with you and you local doctor to reduce the time demands if you live out of town. However there is no compensation involved so there is the issue of travel costs. Under certain very limited circumstances insurance may reimburse for trial participation but I would not rely on that happening.

Gail

Hi Gail, it is amazing at the lack of knowledge on this in the medical field but through people like yourself who are willing to share information things will change. You are really making a difference. I know the doctors at Princeton and Philly are following Jack's case with a lot more attention because of the viral connection, and our surgeon's office has already referred another patient to Hopkins.

I appreciate all your help in finding out about this trial and spreading the word on the HPV 16 virus. It gave us an answer to the "why" question and that alone provides peace of mind no matter what the future brings. Jack and I were happy to meet you and Barry at Hopkins and here's looking forward to a successful conclusion to Dr. Gillison's research for all of us.

One day we'll even be included in those great commercials on the HPV virus. Enjoy your trips.

Regards JoAnne

I talk with Maura Gillison all the time, send me an email and I will send you her contact information.

My husband is a patient of Dr Gillison's and will be starting in the next group of the HPV vaccine clinical trial in January. We will keep you all informed as we begin our next phase.

-------------------------------
Marty, caregiver - stageIV SCC/left tonsil/3lymph nodes/35XIMRT & 35/cisplatin/tarceva-08/06/neck dissection ll/06

Hi Marty --

Is your husband going to be in the second or in the third cohort?

So far so good, no side effects after the inoculation, time will tell if the vaccine does induce an immune response. If so this could posibly help our husbands shed this virus (Dr. Gillison says whether the virus is still present after successful treatment is the 100 dollar question.)

Gail

Hi Gail - He will be in the third. We meet with Dr. Gillison next week. Your updates have been great. We'll have to meet at Hopkins one day or come to Annapolis and have crabcakes!

Testing for HPV was one of the first things my team did when I was 1st diagnosed. Being a young active non-drinking, non-smoking healthy vegetarian, it was the most likely source. And as we expected I tested positive for 16. Thank you guys SOOOO MUCH for your time, efforts, and sacrifices to test this possible treatment. Words cannot even express my gratitude.....

davew

There were a couple of very interesting papers published in December 2006, relating to HPV and head/neck cancer -- both in Journal of Clinical Oncology. One is an editorial by Dr. Gillison and the other a study by Dr. Licitra and her colleagues -- both deal with the difference in behavior and prognosis for HPV+ as opposed to HPV- tumors -- Licitra essentially looked at the biological mechanism for this difference and speculates on how this affects disease progression and patient outcome and also, research (as HPV+ and HPV- cancers could well be expected to respond differently in clinical trials). Gillison expands on this latter point in her editorial. She also suggests that staging and therapeutic approach may need to be modified for the two biologically different diseases. And that HPV status should be taken into account when clinical trials are designed.

Both papers have a great deal of information on HPV +SCC, and a number of citations worth following up on for those so inclined.

Gillison's editoral can be read at:
http://www.jco.org/cgi/content/full/24/36/5623

Licitra's paper is her #2 citation, and can be selected to read.

Gail

Hi all --

Another update on the HPV vaccine trial -- Barry and I went up to Hopkins yesterday for his last injection (of four) -- he also met with the ENT for a check-up and also, they took a lot of what they call "study blood" for immune function analysis. This will all be analysed when all four cohorts (4 vaccine doses) have been completed so some months to come to find out results.

As usual, the injection caused no reactions nor any side-effects. So far so good on that.

The exam by the ENT showed everything still "all clear." It was a very interesting meeting, however - as it was the first time the surgeon has expressed an opinion that HPV positive head/neck cancer probably needs a different therapeutic approach than HPV negative cancer. What he said was, "there is probably no reason to call these patients back in for a neck dissection if they have successfully gone through chemoradiation, as these HPV+ cancers respond so well to that treatment and are unlikely to recur. However, I still want to do a ND on HPV- patients because of their risk of recurrence." Six months ago he would not have said that, in fact he was still a bit "miffed" that Barry had declined ND. Now he agrees it was the right decision.

I also spoke to our chemotherapy nurse -- she said that Hopkins is now testing very HNC patient for HPV and has been doing so for 2 years, She said they are finding the rate of HPV-positive oropharyngeal cancer to be about 70-80% (!!). They have been doing some comparative studies now that patient groups can be separated by HPV status, and these confirm what the ENT said re response to treatment and recurrence.

She also said the "multi-million-dollar" question is: if an HPV+ cancer is successfully treated, is the virus still there (perhaps in a latent state) and can there be -- long-term --problems from this? HPV oral cancers have not been studied long enough to know what happens 10-12 years out. One reason everyone hopes this vaccine works, as one goal is to rid the cancer patients of their viral burden. (And we note, the follow-up for the trial is for 15 years...)

Gail

Gail,

I can't wait to read your follow-up trial posts. Lets see, that will make me a young 74 yr old and I figure I will have appx 15910 posts. What Title will that give me?

Anyone
I was diagnosed with tonsil and neck cancer in in August 2006. I had surgery and follow-on chemo (Cisplatin and Erbitux) and Radiation treatment for six weeks. The Pathologist at Barnes/Washington University said my tumor was HPV 16 positive.

I would like to contract Dr Gillison and determine if I am elible for this study. Currently, Barnes Hospital/Washington University are not part of the clinical trials.

Can anyone provide contact information for Dr Gillison??

Thanks in advance for your assistance

Jos Sabin

This is Off Topic to the HPV, but I just re-read Gail's remark:

"he had his last phoresis a week ago (that's where they harvest white bood cells for the post-inoculation immune response tests) -- a two-hour procedure that the Hopkins people try to make as pleasant as possible but it is hard to make pushing all your blood through a machine and then putting it back in really nice! The movies on a large-screen TV and the body-sized heating pad help."

If you know anyone who is in the habit of donating blood, phoresis is another way to do it, plus you can donate every two weeks if you wish (the cells don't store as well as whole blood, but the body recovers from the process much faster).

It's a way to catch up on videos for 'free' and do some good in the process <grinz> I used to be a regular phoresis donor until they decided to exclude donors who had lived in Europe/UK (Mad Cow concerns).

Sabja,
Here's a link to the Dr's contact page at Hopkins. There is also a link on the page for clinical trials at Hopkins:

http://www.hopkinskimmelcancercenter.org/experts/doctor.cfm?doctorid=276

Good Health,

Chuck

Gail, thank you for the 2-13 update, please keep them coming.
Sharing your story of Barry's recent ENT visit and his change of thinking within 6 months indicates the beginnings of acceptance. The HPV connection is gaining validity. Awareness is growing.
Our story is similar. My suggestion of HPV was dismissed by Mike's team early on. They knew nothing of the connection. No testing was done. Neck dissection was recommend by the ENT after complete response to chemoradiation. We informed him of the studies, publications and current reconsiderations in protocol. We agreed to a time out to think about it and meet later. Our next meeting, the ENT informed us he attended a seminar over the weekend. He now concluded it was appropriate to moniter on a monthly basis due to Mike's complete response and not fitting the tobacco/alcohol/age risk profile.

I thank you and Barry again for your contributions to this important study.
Ginny

Hi all --

Barry ges up today for his *last* visit in this phase of the trial. They will take blood and look at his injection site, so essentially a non-event. We have noticed an increase in forehead/back acne in the week after each injection -- not obvious except to us -- which might mean an immune response or perhaps a reaction to some "carrier" component of the vaccine.

We see Dr. Gillison in June, by then most of the cohorts (dose levels, there is no placebo arm) will be done but not sure when results will be available.

Dr. G. seems pretty confident that we should do well -- the follow-up for this trial is 12 years!

Re recognition of HPV, I have seen far more mention of this on web sites to do with oral cancer than in the year after Barry was diagnosed. However, many doctors are still unaware -- any oropharyngeal cancer, esp tonsillar, should be tested. Dr. Gillison feels tonsillar cancer is probably a "surrogate" for HPV+ cancer, at least in non-smokers.

Hopkins can do the testing if your hospital can't, and they can use the original pathology slides (which are usually kept for 5-10 years) if no tumor sample is available.

Gail

Hi Gail - Rick is just beginning the HPV vaccine with Dr. Gillison so I will keep the info flowing for everyone. We just had all of the premlinary bloodwork, etc. done. Glad to hear it all has gone well. One of these days, we need to meet!

Hi all --

It's been a while since I gave an update (how about one from some of the other Forum folks who are enrolled?)...that's because it's been a while since anything happened.

We met last Friday with Dr. Gillison for a checkup and blood sampling -- she pronounced Barry "healthy as a horse" or words to that effect so that is good news.

Re the trial, all cohorts have been enrolled and they are starting on the last phase -- each dose level (of 4) has to complete their inoculations and Drs have to be sure there are no side effects before going to the next dose, so this takes a while. A bit longer than expected, but it is still going well -- no side effects of any note.

After all the cohorts have had their inoculations, then the hard work of the blood/serum analysis begins and then, analysis of the data. Hopefully this will show that the vaccine does boost immune response to the virus and that the subjects' blood shows reduced levels of HPV markers after vaccination.

This is because the worry is not so much a recurrence of the original cancer, which is relatively low for HPV cancers (at least in the first 5 years), but that the virus could go dormant like HIV or chicken pox and pop up years later to cause more problems. There have been a few patients, for example, who had cervical cancer years ago and now present with oral cancer due to HPV.

Thus the potential for a therapeutic vaccine which will help HPV-infected cancer patients shed the virus.

Gail

Wow I just read this whole thread, thats very exciting news indeed. Glad to hear everything is going so well.

Has there been any research done as to the average timespan between possible HPV infection and when the oral malignancies occur as a result?

There is no answer to your question, and no logical means to obtain one at this time.

Not to disagree, but Dr. Gillison has told us that they suspect the lag time between initial HPV infection and appearance of cancer can range from 5-20 years, she told my husband he probably had the infection 10-15 years before his tonsil cancer developed. Now -- I do not know on what this is based, assume work with cervical cancer as the HPV-oral cancer link is relatively new.

As to how long it might be (if the HPV goes "latent") and then reappears, as Brian says, no one knows and it certainly has not been studied long enough to answer this.

Having said that, I spoke last week to a woman who had cervical cancer (treated successfully) 20 years ago and now presents with a tonsillar cancer which is probably HPV+ (being tested at Hopkins).

Gail

You are not disagreeing with me, but restating essentially what I said based on my routine conversations with Dr. Gillison and others in the HPV research community. Everything is a best guess at this time, and none of those guesses are based in any clinical evidence. I would hardly consider the range of 5-20 years meaningful at all, and her statement reflects what she clearly has stated, they (all the current researches in this realm, not just her team) just have no real knowledge of what the situation really is. We do not even know if it actually goes latent, or if it is that people are constantly reinfected after their immune system clears the virus. For that matter if it does exist in some latent or dormant form, we have no means to detect it with certainty while it is so. We have no clue as to why it seems to persist in some and not in others. Like I said, nobody actually knows very much and there is no data to answer that question from. In your example of the 20 years past cervical cancer patient, there is no means today to know if during that period of time the virus was dormant in her, or if she did not have it at all during that time and was reinfected more recently to her oral cancer diagnosis, or what. Noone can tell you the pathway that a form of the virus might take from cervical to oral, or oral to anal, or anything.... The answer is no one knows enough to do more than speculate on possibilities at this time. I think that Gillison's answer to you of that many years in the possible span described, is her way of saying that she can't really answer your question.

The data is not drawn from the cervical world, as I have been told there is no data published which defines the actual identification of HPV exposure moment (no one until recently has been looking at this because the GYN world has not routinely been testing patients for HPV or collecting data), subsequent incubation time, or the time necessary for all the possible genetic cellular alterations necessary to occur, (and avoid immune system response), to finally become a full blown cervical malignancy. What is not known far exceeds what is known, and the answers are not immediately at hand. The question cannot be answered in any meaningful and useful manner.

Hopefully, the ongoing trials will provide some more concrete information about the progress and management of what seems to be developing as a distinct subset of OC. If the ultimate goal is a cure or vaccine for the causal factor itself... i.e. HPV, and the interim goal is dramatically increased awareness about that factor; then I can guarantee you that throngs of people are going to start asking these and many other questions as it relates to their perceived risk AS that awareness level rises.

For years the mainstay of concern when it comes to STD education has been HIV, which has had the lion's share of attention, and rightfully so. Now the public is being made aware of a new and serious threat, and learning that their risk of developing it is on an order of magnitude substantially higher than they ever could have perceived with any other major STD. We are going to begin seeing an entirely new demographic of concerned individuals that fall outside of the "norm" for what is considered the typical age AND risk factor for this group. And these are people that will want answers to their questions.

I believe that though it should be handled with caution, and despite the fact that is definitely in a preliminary stage, its still pertinent information... I also think Dr. Gillison et al should be commended for their dedicated and expedient response to this crisis. Hopefully the information provided earlier in this thread will prove fruitful and this can be treated from a more chronic standpoint. As a side effect, I believe awareness about the disease as a whole will also increase dramatically, and that is a major step regardless of what factors cause the disease to begin with.

Just my opinion of course.

Hi all --

Just another quick update on the HPV vaccine trial at Johns Hopkins. We met with Dr. Gillison again for the routine 3-month check-up (everything good) and she told us that the final cohort would be through their vaccinations in a month or so. At that time they will start doing the analyses of the blood samples, which will show whether the vaccine results in an immune "boost" against HPV and if this boost is dose-dependent. Barry got the second dose level of 4, there was no placebo arm. No one has had any side-effects.

If the results are positive, the Phase II trial will be designed. Not sure what this will look like, that is, whether it will include patients with active HPV+ cancer.

Well, we are off again on another trip -- this time to Uganda for birdwatching and also, Gorilla trekking. Leaving Friday, back in a month. Just remember, there is life after this disease! Barry and I wish everyone well and "see" you in September - which will be exactly two years after the end of Barry's treatment so a big milestone!

Best,
Gail and Barry

Thanks for the update and have a great trip.

Take some pictures for me.

I'm thrilled that you guys are enjoying "life".

Jerry

Boy, Gail, do I envy you. Gorillas are one of my favorite animals. Have a blast!! Amy in the Ozarks

My husband has just completed the HPV vaccine trial at Johns Hopkins. He has not had any side effects. He was part of the last cohort. Gail we found out about this study by your post here, and I want to thank you for your dedication. We presented testing for HPV to the oncologist and he was happy to have the test done for this. I encourage any new members to become active in your treatment and treatment options, many physicians will listen to your input, some will not but it is worth giving it a shot.

Hi all --

I certainly hope that the vaccine will prove to work -- there have been some articles this summer on the potential of vaccine-mediated treatment for virally-induced cancers and all state that this may be the treatment of the future. Certainly the cell-culture study by Rampias which found that, once the HP viral genes were deactivated, the cancerous cells died quickly, is promising. We know this is undoubtedly years away. Still, as Haddad wrote after the 2007 ASCO meetings (in his summary of HPV and head/neck cancer presentations):

"Research in this area is still preliminary, and previous experience has proven this field to be quite challenging. Nevertheless, newer technologies might make this possible, and the approach described by Rampias and colleagues[12] is promising. If targeting [of viral genes]proves feasible, these findings will have represented a major breakthrough. The ability to treat these cancers without chemotherapy and radiation, but instead with gene therapy and antiviral therapy, is certainly appealing, but we expect that it will be a long time before we see this work come to fruition. In the meantime, our focus should be on fuller utilization of the HPV vaccine and public education measures.

Conclusion
HPV-related head and neck cancer represents a new entity that is now well defined. The practicing oncologist needs to be aware of these new findings, and HPV testing, with PCR or FISH, should now be performed routinely. For now, results will have significant prognostic though not therapeutic implications. Still, changes come rapidly in this field, and we expect that different treatments will be available to these patients in the near future."

Gail