Clearance, persistence and recurrence of HPV infection

for you ladies who have had LEEP or cone for treatment of CIN2-3, this abstract may be of interest. (bearing in mind that medical studies sometimes contradict their findings, I have found that most studies argue that HPV negative status 6 months after the conization has 100% of negative predictive value of recurrence, while I found one article that said that some HPV negative women still had recurrence). Anyway, this abstract lists the factors related to presistence of HPV, but more importantly, it says "that "recurrent" HPV infections offer no evidence that the recurrent episode is correlated with reemergence of the same strain or another strain of the same genotype (wild or variant), but the sequential detection of other HPV type is common. The studies offer no evidence of competition between HPV types but frequently show an increased risk of acquisition of new HPV types in patients already infected compared with those who are HPV-negative."
Seems that this study gives some support to the vaccination after LEEP, b/c it found no evidence of recurrence with the same strain of virus (no evidence of dormant virus "waking up"), but they think recurrence is caused by new infection of different strain, while women who have had precistent HPV in tha past, are more in higher risk to get a new infection. I think this confirms that if vaccination protects from other strains than the one you had, it makes sense as it would protect your from getting new infection in the future. What are your thoughts?

Denis F, Hanz S, Alain S.
Service de bactériologie-virologie-hygiène, CHU Dupuytren, 2, avenue Martin-Luther-King, 87042 Limoges cedex, France. francois.denis@unilim.fr

Cervical HPV infection is a common sexually transmitted infection. Most women are infected shortly after beginning their first relationship, with the highest prevalence seen in women under 25 years of age. Thereafter, prevalence decreases rapidly. HPV infections are usually transient; but several factors increasing persistence were identified as host factors (genetic or acquired as age, immunodepression, oral contraception, smoking) and viral factors (genotype, variants, viral load, integration...). Although it is now widely admitted that a persistent infection with a high-risk HPV type is necessary for the development of high-grade cervical intraepithelial neoplasia and invasive disease, whether persistent HPV infections are characterized by the continuing detection of HPV, or by a state of viral latency during which the virus remains undetectable only to reappear later remains unknown. The distinction between a persistent and transient infection is arbitrary depending from both the time of sampling in relation to the natural history of the infection and the interval between samples. The longitudinal studies show that "recurrent" HPV infections offer no evidence that the recurrent episode is correlated with reemergence of the same strain or another strain of the same genotype (wild or variant), but the sequential detection of other HPV type is common. The studies offer no evidence of competition between HPV types but frequently show an increased risk of acquisition of new HPV types in patients already infected compared with those who are HPV-negative.

http://www.ncbi.nlm.nih.gov/pubmed/18417407?ordinalpos=34&itool=EntrezSyste m2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDo cSum

By corellin
Posted May 10, 2009 at 11:47 am
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Hi Pirkar -- Thanks for sharing. Yes, in my view, that's a good argument for vaccination, since you're unlikely to have been exposed to all types. Also, both Gardasil and Cervarix "cross react" with some of the other types, so they do provide some protection from the "non-vaccine" types. Both the vaccines show good antibody response for women aged 26 - 45 and good protection for viruses they don't already have. It doesn't seem like too many researchers are overly-enthusiastic about the benefits of those vaccines for older women, but, hey, they haven't personally experienced a bad outcome! I still haven't gotten the vaccine myself, and, mainly, it's because I'm wondering how it will affect immunity for the virus I already have. According to the research, though, it makes absolutely no difference one way or the other for a current infection.

By Sophie-1977
Posted May 10, 2009 at 10:29 pm
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Hi Corellin,

I've also had hesitations about getting vaccinated, not just because stories of even a couple of bad reactions are scary. I've never had a problem with vaccines but I hear that Gardasil causes a few more problems than some others. Here's a link on a slightly higher than usual association between Gardasil and Guillain-Barre syndrome, although Merck isn't calling it an association. See what you think, because Web MD uses a title that sounds alarming:
http://www.webmd.com/cancer/cervical-cancer/news/20090430/gardasil-linked-t o-nerve-disorder

But my real question about Gardasil or Cervarix, if it's approved here, would be its effect on existing HPV infection. For myself, I'd like to make sure I get confirmation of negative HPV status right before getting this vaccine -- the hour before, if possible! -- because the Gardasil trial did show something odd in 1 of the cohorts that went in testing positive for HPV 16 or 18. If you look at the vaccine research paperwork ("VRBPAC Background Document") you see on pp. 13-16 a discussion of the possibility that Gardasil would somehow "enhance disease" among people already affected with the types the vaccine covers. This seems completely counterintuitive -- why would a vaccine that stimulates antibodies against these viruses make the viruses worse? However, one small HPV positive subgroup in the trials really did appear to get worse instead of better after receiving the vaccine, and the researchers tried to figure out why -- was it because more of them were smokers? etc. They didn't have any conclusive answers.

I'm going to look for a link to this vaccine trial document now and will post it.

Sophie

By Sophie-1977
Posted May 10, 2009 at 10:37 pm
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Hi everyone,

Here's the link to the Gardasil vaccine paperwork filed with the FDA:

www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4222B3.pdf

The cohort in question was "study 013" mentioned on pp. 13-16 and again in summary on p. 25. In this small group, the HPV positive recipients of the vaccine were more likely to develop CIN 2 or 3 lesions than the HPV positive subjects who received a placebo shot.

Does anyone think that the age cut off for the FDA approval of Gardasil is due not just to the vaccine's preventive purpose, but also to the possibility they haven't quite figured out whether the vaccine could enhance disease in people who already have one or more of strains covered by Gardasil? It's puzzling to me.

Sophie

By Daphne75
Posted May 11, 2009 at 10:47 pm
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Hey Sophie,

I've wondered too if the reason Gardasil's approval for women over age 26 keeps getting denied is because it does in fact increase the chances for infection to get worse. I had the vaccination three years ago and was just diagnosed this year with AIS. I was 30 at the time of the vaccination and had never had an abnormal pap before. I've never heard of this happening to anyone else, so maybe I'm just an isolated case.

By jamiegirl
Posted May 11, 2009 at 11:09 pm
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I think that part of the problem is that the thinking is that many women, by the time they are 26, will probably have already contracted one of the four strains of the infection which the vaccine covers, so it wouldn't help. Maybe once the new HPV 16/18 test gets used more commercially now that it is approved, it will pave the way for the approval for Gardisil in women over the age of 26 so they will know who has what strain and who the vaccine would benefit. Maybe I'm just being naive????

By Sophie-1977
Posted May 12, 2009 at 12:05 am
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Jamiegirl,

I agree with your assessment about the exposure of most women to HPV before they're 26, and I share your hope that more targeted HPV tests can clarify a lot of things. I remember being stunned 2 years ago when I looked at my test results and saw that I'd tested positive "for 1 or more of the following," which was followed by a long list of numbers. What on earth?? I couldn't believe that there was no test that would specifically identify HPV type(s).

Perhaps the availability of such a test will prompt the FDA to approve the vaccine for older women. This could be true whether the FDA is worried simply about which women would benefit, or whether there's some real lack of understanding over the vaccine's effects on someone who's positive for one of the strains it covers.

I still wish I knew a few HPV experts who could give me their opinions on what happened in that mysterious subgroup 13 who got worse after getting Gardasil.

Sophie

By tam1
Posted May 12, 2009 at 8:15 am
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This is what I think of subgroup 13 in the study. Nothing in this world that we do is without risk. Getting in your car and driving carries some sort of risk. I do think the results from this group warrants futher study. Also the FDA has determined a womans benefit from the vaccine outweighs the risk. There are going to be women who get this vaccine who are positive for one or more strains that it protects because there is no type specific testing (well i guess now there is new test for this recently). This reminds me of the theory that childhood vaccinations can bring out autism in some children who are predisposed to it. But at the same time measels, mumps, etc is a big threat without the vaccinations.

By Pirkar
Posted May 12, 2009 at 8:34 am
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Hi, thanks Sophie for sharing the study. Tam, there is a type specific HPV DNA test although it is not approved in the States, but in several European countries it is.
Corellin, would you know any studies that indicate that vaccine would be safe for currently HPV-negative women who have had active virus in the past (and who have been able to supress it by their immune system, either prior or after conization)?
Sophie, there may be a HPV test available that measures current active infection, but don't you think that vaccine may be dangerous also for women who currently test negative (because their immune system has supressed virus, and viral load is too low that it would cause dysplasia and be visible in the test), but have had active infection in the past? So women, who have had HPV 16 or 18, and who developed CIN 2 or 3, but whose immune system supressed the virus (either by itself or by the help of conization that removed the dysplasia and active virus with it), may develop again dysplasia since their recurrent virus wakes up? I do not think this is logical, although it may be possible. It is not logical because:
1. vaccine cannot infect you with new virus, it only causes more effective antibody development (in the blood I guess?),
2. some studies in my understanding have indicated that if one gets new infection (which you cannot get from vaccination), while you have dormant HPV (meaning, you have been infected in the past but currently do not show infection as measured by HPV DNA test), you are in higher risk of developing new infection.
So theoretically I do not see possibility that vaccination could infect you again if you currently test negative. But according to this logic, your infection could not possibly worsen even if you test positive, because vaccination does not infect you. Or perhaps, the present or dormant virus "thinks" that vaccine is actually a new virus and thus, reactivates? This does not seems very likley though. Thanks a lot for this link and your ideas, at the moment I tend to believe that vaccination cannot worsen your dormant or active infection - or it it can, what would be the mechanism?

By jamiegirl
Posted May 12, 2009 at 11:02 am
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Pirkar - I had posted this in some of the discussions on anal hpv here- don't know if you read them. I had an anal pap and hpv test recently by a doctor in NYC who deals with hpv and hiv all the time, as his clientele is mostly the MSM crowd. He told me that if my body clears the infection, I should absolutely get the HPV vaccine to prevent future infections, even of the same type that I have. He said there are studies that have shown this to be effective, and that there will probably be approval soon for the vaccine to be available to those over 26. He also said that as soon as it is approved for boys, I should get my son vaccinated. I was thinking about it this morning, and one of the reasons it is probably not available yet for men may be that there is no way to test if they have hpv, unless of course it is in their anus. Obviously, if they are positive for it on their penis but couldn't be tested for it, the vaccine would not help them. I do think boys should be vaccinated before they start sexual activity. My 11 year old son was talking to a 16 year old boy and asked him if he ever had sex. The 16 year old told him that he's had sex with 4 different girls. If that kid doesn't get vaccinated soon, he's a breeding ground for girls who haven't been vaccinated. Hopefully he's still clean....

By sia
Posted August 19, 2009 at 2:58 pm
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hi i red that it's not a good idea to get the vaccine while your virus is active cause vaccines in general suppress the immune system if you manage to clear up the virus i find it a good idea to do it cause the highest risk you'll have is the vaccine being less effective than being taken proactively

By marsha123
Posted August 19, 2009 at 3:16 pm
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There was some misleading information on my local TV station yesterday about the "dangers" of the Gardisil vaccination, incuding an interview with an ob/gyn who said he wouldn't give the vaccination to his 11 yr. old daughter. (He probably intends for her to stay a virgin till she's married too, huh?) Did anyone else see this segment? Part of the opponents' argument is fueled by assusations that Gardisil has caused several deaths, which proponents of the vaccine say occured in young women who clearly had other serious medical conditions. Again, all of this is obfuscating and trivializing the seriousness of this condition which ALL OF US KNOW is anything but trivial. M

By sia
Posted August 19, 2009 at 3:48 pm
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By dazednconfused
Posted August 20, 2009 at 12:09 am
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Marsha - I just read about that news segment online. I also found it frustrating. While looking it up, there was another Gardasil-related story from the same day (yesterday) stating that the risks of the vaccine were few and generally minor.

By dazednconfused
Posted August 20, 2009 at 12:12 am
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And Pirkar, this is a timely post for me, because, although I am officially WAY too old, I was planning on asking my doctor about the vaccine if my post cone checks were negative (even though there is no sex on the horizon, probably for the rest of my life...). Actually, the first step is to find a Dr. who will do HPV tests rather than just paps, but I had been wondering the same thing about Gardasil for adults.

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