Meet the Herpes Family, Warts and All
Herpes is a family of many different viruses, literally dozens of them, but only 9 of them are of importance in humans. Perhaps the most widely known members are Herpes Simplex types 1 and 2; Epstein-Barr virus (EBV), which can cause infectious mononucleosis (“glandular fever”); Cytomegalovirus (CMV) which infects between 50% and 85% of adults in the United States by 40 years of age, and Varicella Zoster virus (VZV) which causes chicken pox — as well as shingles. Human Papillomavirus (HPV) causes warts (including genital warts) and some varieties of HPV cause cervical cancer in women.
I have written before about EBV and CMV. This article will focus on HPV – and its potential connection to secondary cancers in CLL patients.
Human Papillomavirus (HPV)
There are many varieties of HPVs. As a group, they can infect the skin and mucous membranes, causing different varieties of warts. Infection is often through direct contact but it is also possible to get infected by touching a surface that is contaminated with the virus. It is also thought to be possible for a person to infect themselves, spread the virus from one location to another by touching.
Genital infection (leading to genital warts) is caused most often through sexual contact. In the last few years there has been breath-taking progress in our understanding and preventing majority of cervical cancers in women. Turns out some varieties of HPV are responsible for a large percentage of cervical cancers, and we now have a vaccine that can prevent infection. How cool is that! I do not know about you, but if I had a young daughter about to explore her sexuality, I would make sure she is protected from potentially deadly cervical cancer down the road due to HPV infection.
As with all members of the herpes family, once an individual is infected, traces of HPV stay in the person’s body for the rest of his / her life. In healthy individuals the virus is kept under check by an active immune system. We know by now that CLL patients are very likely to be immune compromised, especially if they are late stage CLL patients or they have been through immune suppressing chemotherapy. T-cells are frontline troops for keeping pesky viruses under control. Drugs such as Campath and fludarabine cause massive reduction in T-cells counts and their efficacy, allowing viruses to use the window of opportunity and grow unchecked.
On a personal note, my husband PC had beautiful hands – well shaped with long, artistic fingers. Several years after his CLL diagnosis, I noticed he had these flesh colored bumps on the back of his knuckles. I had no idea what they were. Our dermatologist later told us they were common warts, caused by HPV. The picture alongside is what it looked like, more or less. If you don’t mind getting scared or grossed out, just type the word “warts” into Google and look for images.
Among the drugs used to treat genital warts are anti-viral drugs such as famcyclovir (“Famvir”) and imiquimod (“Aldara”). You should be familiar with both of these drugs by now. Famcyclovir (and its kissing cousins valacyclovir and acyclovir) are highly recommended as prophylactic medications to prevent a bad case of shingles (caused by Varicella Zoster virus) in at-risk CLL patients undergoing immune suppressive therapy. In addition to treating aktinic keratosis (pre-skin cancer), Aldara is also FDA approved for treating warts, the genital variety. PC was already taking daily Famvir. I bugged the doctor until we got a prescription for imiquimod (not a cheap drug by any stretch of the imagination!) and made sure PC put a tiny dab of the ointment on his knuckles. Over time, I was relieved to see the warts faded away.
HPV and Secondary Cancers
Below is the abstract of a very recent article from Ohio State University that makes a connection between HPV infection and secondary cancers (especially skin cancers) in CLL patients. Send me a personal email if you need help locating the full text of this article.
Br J Haematol. 2010 Mar 8.
Second malignancies in B-cell chronic lymphocytic leukaemia: possible association with human papilloma virus.
Flynn JM, Andritsos L, Lucas D, Byrd JC.
Division of Haematology and Oncology, The Ohio State University Medical Center, Columbus, OH, USA.
Second primary malignancies have long been associated with chronic lymphocytic leukaemia (CLL). We assessed secondary tumour samples from CLL and control patients for the presence of human papilloma virus (HPV). 132 CLL patients with 44 second malignancies were compared to a matched randomly-identified control population of 264 non-CLL patients with 54 solid malignancies. Polymerase chain reaction was performed with the highly conserved MY09/MY11 HPV primer. None of control samples were HPV-positive, while 53% of samples from the CLL group were positive. This report describes preliminary evidence for the presence of HPV in secondary malignancies, in patients with CLL.
PMID: 20230400
In this study a total of 132 patients with CLL were examined, compared to an age, gender and ethnicity matched population of randomly chosen control population. 44 out of the 132 CLL patients (33%) developed secondary cancers. This is consistent with many other studies done in more recent times. But I have to admit, the 33% number caught me by surprise as well.
The authors point out that CLL patients have poor immune function, similar to patients who have been through organ transplant and treated with immunosuppressive drugs to prevent graft rejection. Organ transplant patients are also more prone to development of secondary cancers while they are on immune suppression drugs. This is particularly true for squamous cell carcinoma of the skin, which occurs much more frequently in CLL patients as well as solid organ transplant patients.
Now for the interesting part: human papilloma virus (HPV) has been associated with skin cancers in solid organ transplants than in otherwise healthy patients diagnosed with squamous cell carcinoma of the skin. Can the same thing be happening in CLL patients as well? Are our guys more likely to get skin cancer because their immune compromised state allows HPV to flourish unchecked? This is an important question because if we know the root cause of the increased incidence of secondary cancers, we can hope to do something about it.
There were 9 cases (7%) of localized skin cancer in the CLL patient group. A similar percentage of skin cancer patients were identified in the control group as well. Five of the skin biopsies of CLL patients with skin cancer were also positive for local HPV infection, while none of the control group had skin cancer that was HPV positive. The difference between CLL and normal control patients for HPV association with squamous cell carcinoma of the skin was highly statistically significant.
By the way, there were also two prostate cancers and one colon cancer as secondary cancers in the CLL patient group that also tested positive for HPV. So, it seems the risk of HPV driven secondary cancers in CLL patients is not restricted to just the skin. Remember, HPV is capable of attacking all mucous membranes, not just skin. There are well over 120 different types of HPV capable of infecting people and their ability to cause ano-genital cancer, laryngeal papillomas, head and neck cancers, carcinoma of the uterine cervix etc has been well documented.
Studies looking at kidney transplant patients have shown that up to 79% of viral warts, 42% of premalignant keratoses, and 43% of invasive squamous cell carcinoma contain tell-tale signs of HPV infection. Many of our guys are in the same boat as these kidney transplant patients, with similar or even worse levels of immune suppression.
For now, here are some thoughts buzzing around my head after reading this article, ideas I would like to bring to your attention:
- Many thousands of patients with genital lesions and even “cold sores” have been on daily Valtrex, Famvir etc for many years now, to control of these viraly driven lesions. These drugs have a long track record of safety and efficacy.
- Should “at-risk” CLL patients be on these medications as well, to prevent shingles and herpes simplex inspired sores on lips and genetalia? Perhaps protect against HPV driven secondary cancers? There is no evidence that Valtrex and its kindred are active against HPV. I am just asking…
- It is interesting that imiquimod (Aldara) is FDA approved for actinic keratosis (pre-skin cancer) as well as HPV driven genital warts. Hmmm. A drug that is good for HPV driven warts as well as skin cancer. Makes you think. Like, you know, the same thing that is causing the warts is also likely to cause skin cancer – and what is sauce for the goose is sauce for the gander as well?
- As the authors of this study point out, immune modulating drugs (drugs that modify how the immune system works, not just deaden it as do many conventional chemotherapy drugs) may become more important in preventing deep immune suppression and therefore increased risk of secondary cancers. I was not an early fan of Revlimid – but I am really beginning to change my mind about this immune modulating drug. I especially like it that T-cell and NK cell function is thought to be improved due to Revlimid therapy.
- As most of you are aware, there is already a vaccine that protects young women against majority of cervical cancers driven by HPV. Hopefully researchers will continue to develop vaccines against other forms of HPV that trigger secondary cancers in immune compromised folks like CLL patients.
- Here is a quote from a recent article in Scientific American:
“Researchers have for the first time shown that as many as 1.3 million cases of cancer a year may one day be successfully treated or even prevented by targeting and destroying the viruses that cause them” - In the mean time, do sit up and notice if you develop warts on your hands, soles of your feet etc. Make sure your dermatologist gets told about it. Look up “warts” on Google images so you know what they look like, more or less.
How much of an impact do second cancers have on overall survival? How many patients die from the second cancer triggered by CLL, even if they get a ‘pass’ from the CLL itself? That, my friends, is the subject of my next article. Writing this article has been a nice diversion from the chore of packing. I am surrounded by dozens of half-filled packing boxes and mounds of paper that needs to get shredded. Out of chaos comes order, I tell myself., and it is time I got back to restoring order in my chaotic home and life.
20 comments on "Do Viruses Cause Secondary Cancers in CLL Patients?"
It’s funny but I was just about to go and see my GP as I am getting lots of warts on my hands and was convinced it was from my CLL challenges.
I have been in remission for about 34 months after FCR and these little nasties have been spreading more aggressivley over the past 6 months.
I have felt so good that it took a while for the so called penny to drop.
Very timely article
Thanks Chaya
Derek
Just a quick question. In the 6th grade I had a huge papiloma on the knuckle of my big toe. It was miserable to wear shoes. Had to cut a hole in them. It was eventually, over a long period of time, burned off…equally miserable. Later in life about 30-ish I went barefoot in our 1850s house basement and got gobs of warts all over the bottom of my feet.
Question: Does this virus completely leave the body, or can it survive, dormant like the miserable chicken pox.
Which reminds me that after a months vacation returning Jan. 5 I noted that my WBC had gone from 7 to 17, more than doubling since Nov. Then I got shingles. I have never had any treatment except for IVIgs. (Lucky I caught it the first day) The PHN was most annoying.
Good article and one that I will pass on to friends with other issues that this might address.
Thanks. Fran
Just finished 28 fractions of rad for excised SCC exhibiting perineural invasion that emerged during FCR therapy. Also just had 3 AK’s frozen and I’ve had HPP.
Add me to the list.
Thanks Chaya – Hyper vigilance will keep me alive thanks to your research.
Franc:
HPV is a gift that keeps on giving. Once infected, traces of the vaccine remain dormant in your body for the rest of your life. As long as your immune system is able to take care of it, no problem. But it may show its ugly face and grow out of control during periods of immune function vulnerability.
This is pretty much the standard operating procedure for all herpes viruses. Nasty stuff.
I am a 15 years cll patient untreated. I feel pretty good most of the time. I noticed that when I am under stress, I develop cold sores on my lips.
I am also prone to skin cancers. Your article helps me to understand what I am going through.
Thanks Chaya for your great articles.
Monique
Are verrucas on the bottom of feet warts? From just one I now have about 20. My podiatrist has said to leave them alone but they can be painful to walk on. I have been taking Aciclovir for CLL since 2002.
It is also interesting that before my diagnosis of CLL I had a cone biopsy for pre-cancerous cells of the cervix. 2 years later, after being diagnosed with CLL, I had a return of the pre-cancerous cells. Since this 2nd operation I have been OK. Ladies, please get yourselves checked out.
Thanks Chaya for your wonderful articles. I really appreciate the time you take to decode something so that I can understand it. Bless you.
Sylvie
can my wife get planters warts on the bottom of her foot from me ?. I have CLL. I do not have warts(anywhere) and have NEVER had them. I am in stage 0. I am 52 and I am in the wait and watch level of CLL. I also have Hep C. Did the treatment 7 years ago and it went away for 6 months after 10 months of combinataion therapy. But it came back. I am in the lets just watch it stage of Hep C also. Levels are pretty low.. any suggestions or comments are welcome. Thank you
Chaya,
Thanks for this article. There is a lot to ponder here. I had stage 1 endometrial (uterine) cancer shortly before my dx. of CLL. It was caught very early and I was lucky. When the CA. was found, my docs were suspicious of CLL and within the yr, I was diagnosed. My heme/onc. beleives my uterine cancer could have been a 2ndary CA. to my CLL although my grandmother died of uterine CA but CLL could have influenced its emergence. We have to be so vigilent re. 2ndary cancers and skin cancer.
I think your next article will be very important and could be another eye opener to us all, how many CLL patients die of 2ndary cancers.
My sympathies with your packing chores, it ties in with many memories but I know you will do well on the east coast. Not enough ways to say thank you.
Chris R
Adks NY
After I was Dxed for about 4 yrs my WBC increased from normal to the low to mid 20Ks. Durng that time I started to develop warts on my hands. At about the 4 yr mark I got a case of shingles. My GP treated the shingles with Acylovir 800mg 5x a day. I’m not sure what effect it had on the shingles, but the warts disappeared in days and (knock on wood) my WBC has been pretty much stable since. I’m now at 8yrs since DX.
John
Interesting article, as always. For the past few years (now I think of it, almost coincident with my CLL diagnosis) I have had a single wart on one of my knuckles. I treat it with various over-the-counter treatments but it soon returns. I am also very prone to skin cancers – there seems to be a fresh one to remove every year when I go for my skin check. Reminds me too that it’s time for another pap smear! It seems that even if the CLL is not causing too many problems in its early stages we are sentenced to constant vigilance and visits to various doctors! For those who are interested, it is the work of Dr Ian Frazer at the University of Queensland here in Brisbane that developed the cervical cancer vaccine. He continues to work on HPV-related cancer.
http://www.di.uq.edu.au/profile-frazer
Julia, Brisbane, Australia.
Chaya,
When you say these drugs have a ‘long’ track record, I wonder how long is long? Are we talking twenty years or less? I thought these drugs were relatively new on the block, am I wrong?
I’m sure house clearance is good for the soul – good luck with it.
Molly
Molly:
I guess “long” is a relative term.
Most of the new drugs in use for treating CLL are so darned new, some of them less than a year old (if the clock is started from the date of FDA approval) that anything more than 10 years (give or take a little) in the marketplace has a “long” track record – to my way of thinking.
Terry had painful warts around the same time of his CLL diagnosis.
I have Herpes Simplex-I in one eyelid. After a flareup in 2004 it spread into my eye, next to my cornea. Since then I’ve been on Valtrex for control and stay on it for both control and to protect Terry.
I’ve had only a dozen flares in 45 yrs, since knowing Terry. It is great to not fear allergy season and flareups that Terry could get. We use separate towels and washcloths and I use care to avoid any spread of tears or eye secretions. Further suggestions would be appreciated.
I am concerned enough from your article to ask Terry’s oncologists to further examine the cause of his chronic cough. He just began the second antibiotic for bronchitis, but he coughs any time he eats, drinks and other times. He’s a non-smoker. Hmmm.
Thanks Chaya, for the information. We look forward to your next article.
If you need any moving advice I moved 53 times before marrying young to a Navy man. I am an expert.
Linda
Oh yes, I do know about the forever-lingering herpes virus. But what about the papilloma virus? Is it still lingering somewhere? Can it flare up without a new exposure?
On another note, I notice that a lot of people take Valtrex, or one of its siblings, all year long. Is there no problem with that? As mild as my case was (only 3 blisters opened), I was miserable and can’t imagine having it again. But this is not on topic…I realize, sorry.
Again, thanks. Fran
I developed extensive warts on my hands and arms after a course of Campath which left my T cells depleted for over a year. Aldara had little effect probably because it requires an intact immune system to work. The dermatologist is currently trying vitamin A and urea.
Chaya, please comment that warts and shingles are caused by different viruses and acyclovir will not help HPV (warts). I’m curious that my warts are progressing despite recovery of T cells – wondering if the immunity of the “new” T cells does not recognize the warts. Anyone wanting an eye-opener should search “tree man” on You Tube!
franc:
HPV (papilloma virus) is also a member of the herpes family, as mentioned in the article above.
bmalkiel:
And I also reported in the article that HPV causes warts while shingles is caused by another herpes virus, the Varicella Zoster virus (VZV). Devil is in the details, people.
Unlike broad spectrum antibacterial drugs, we do not have broad spectrum antiviral drugs. But sometimes the edges seem to blur a little. Valtrex (and its kissing cousins such as famvir etc) works against VZV (shingles protection) and it is also approved for oral and genital herpes (usually caused by herpes simplex virus). I doubt it is effective against HPV.
The above article mentions imiquimod “Aldara” for the treatment of warts. I would like to add that it can be used also to treat basal cells carcinoma. I repeat treatment of basal cells carcinoma.
Soon after a FCR treatment I had such a carcinoma on the tip of my nose. In order to avoid a surgery that would have left an uggly scar, the dermatologist proposed a 6 weeks treatment by Aldara (normal treatment length). He explained that this medication works by stimulating the efficacy of the T-cells.
Of course as a CLL patient it did not work as fast, but it worked. After 13 weeks the tumor had desappeared.
Chaya, thank you for the help to all of us, you are a wonderful lady.
Background: 43 yrs old, 4 years since dx and I had one round of Rituxan-only treatment a year ago. That knocked my WBC back from 350k to low-teens. I am now ready to do another round of (as yet)undetermined treatment as my WBC is climbing again. I have had recurring problems with common and plantar warts for years. My dermatologist is about ready to throw in the towel! This post was of particular interest to me as this particular “nuisance” is one of many that we have to deal with in our CLL journey. Infections, viruses, secondary cancers… fun all the time. I will use this to talk to my dermatologist and my Onc about possible treatments to try to get rid of these gross things. Thank you!
Hi,
Have had CLL for 4 years. No real problems. However I had a wart that was burned off 2 years ago and refuses to go away with the treatment recommended by dermatologists. (Uptons Paste). Should I be worried. Should I look at Aldara?
Abu Rizwan
Recap: I’m an 86 year old CLL survivor without teatment for 21 years. Most of this time I’ve required treatment of actinic keratoses of my face and scalp—zapping with liquid nitrogen. Currently my dermatologist is recomending Levulan therapy and I have preapproval for insurance coverage, but it’s still costly for my budget. Do you or others online have knowledge or experience with this procedure and outcome?
Thanks much, Chaya, for sharing your expertise.
DEL
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