Hi,

Do HPV research DNA tests (HC2, PCR, etc) have the potential of detecting "dormant" HPV? In this case, my definition of dormant assumes non transmissible. I'm asking because I used to have HR- HPV that cleared and have noticed NIH redetection/reactivation articles out there, specifically for older women.  Is it possible that these HC2 and/or DNA PCR detection are picking up on DNA that is inactive? Again, I'm specifically asking about DNA tests (ignoring RNA PCRs for now). I'm just hoping this is a possibility in an effort to make myself feel better. Perhaps not all of these (if not most) redetections are not actually non transmissible dna material

I'm not a pro and this isn't my area so wanted to ask you all. Thank you.

In other words,
is it possible that when studies note "hpv detection" in older women that perhaps some of this is due to latent/dormant HPV that does not necessarily mean transmissible. Would the cutoff value for these tests make it to where this is not the case and all positives would imply active infection?

I'm asking this question in cases of normal cytology hpv positive in research studies of older women

Welcome to the Forum, thanks for your question(s).  I'll try to help.  Your question is a tough one as it deals with a topic of ongoing research.  The short answer is that following clearance of HPV DNA tests from a person who had infection previously detected, as is typically the case, the risk for subsequent forward transmission if very low.  Typically when commercially available DNA detection tests show that HPV has cleared, careful study over time, sometimes using ultrasensitive tests for HPV DNA show periodic, intermittent "shedding" of viral DNA. The significance of this low-level, intermittent shedding is the topic of ongoing research.   Most experts counsel women that clearing of detectable HPV means that those persons are unlikely to transmit their infections to others and they are at very low risk for progression to pre-malignant cytological changes.  This I suppose there is some slight risk for transmission to sexual partners and little or no risk for progression to cancer, particularly if the person continues to get periodic sexual health check ups including HPV testing. and I would not worry about transmission to new, uninfected partners. 

I should add that I note that in your first question you mention hybrid capture tests.  these tests are clearly less sensitive for detecting evidence of current or past infection when compared to other amplified DNA or RNA detection tests. 

The best prevention of transmission to uninfected partners remains vaccination.

I hope this information is helpful.  EWH

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Thank you for the response. I'm familiar with HPV "shedding".  I have a bit of a background in virology, and I personally think it's odd for HPV to "shed" decades after clearance. I can see this being a potential for the first 3-5 years or so after clearance, possibly even within 10 years post clearance, but not longer.  After all, this virus is very different from HSV where the shedding is conceivable and makes sense given the mechanics of that virus.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2698799/

The data on capital HPV shedding overtime are still emerging. On the other hand, we absolutely know that for other chronic viral infections such as herpes, shedding can occur decades after the initial infection although the frequency of that process the clients overtime.  Studies of HPV are ongoing.---

I appreciate your answers. Seems like what I'm asking is unknown. I do feel, however, that if it was indeed a high possibility, then the data would be there simply because if something (post clearance transmission) occurs in large noticeable numbers, we would be prompted to investigate. Regardless, I will take your advice for now, hoping new research doesn't hit us like a brick later down the line.

You ask why I was so focused on the HC assay? Because that is what my linked article used to detect hpv in older women. Thus, it seems that, based on your answers, these does indeed represent viral replication - noted.

Here is the original article I linked to you :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2698799/  uses HC2 and Digene Microplate Luminometer 2000 (DML 2000^™) to detect HPV

It might be interesting to contrast the above article  to this one
"The persistence of virus in these samples cannot be attributed to a latent infection as usually defined⁶. Implicit in the definition of viral latency is the capacity to synthesise new viral progeny. HPV genome integration marks the end of the virus life cycle and the loss of this capacity, consistent with the absence of HPV16 E4 expression, a viral biomarker of productive infection, in these samples... we believe we have provided the first robust estimate of the prevalence of silent HPV16 DNA in morphologically normal cervices of older women...Our findings help illuminate a number of previously puzzling aspects of the exposure-disease relationship in older women^24,25,26. The observation that HPV positive older women are less likely to have a contemporaneous abnormal smear than HPV positive younger women could reflect the emergence in later life of integrated but transcriptionally silent high-risk HPV types."
This article uses Luminex PCR

Again, this is a lot. I will more than happily purchase a second question for this. I think it would be good to quickly glance at both documents. Given my brief stint with virology as well as personal experience with HPV, this is interesting for me and I need help interpreting the above.

Thank you again.

I have reviewed the second article you provided a link to but am unable to successfully open the link to the first reference you provided.  The second article uses research techniques which are not commerically available to explore the issue of HPV latency but acknowledges that interpretation of the results are challenging and that HPV nucleic acids found in cervial tissue in their study may or may not be replicable.  All nucleic acid detection tests detct only a small fragment of the targeted DNA (or RNA) and thus may detect replicable (viable) organisms of non-viable nucleic acid fragments.  When nucleic acid fragments are present the body typically processes and elimantes them over time.  Thus for virus that has cleared, the closer to the time of clearance (or treatment in other cases), the more likely it is that the nucleic acids represent non-viable, residual nucleic acid fragments that have not yet been eliminated.  It would seem that the more distant in time that nucleic acid fragments are detected, irrespective of which detection test is used, the more likely it is that the presence represents replicable virus.  As I said in my original response however, "The significance of this low-level, intermittent shedding is the topic of ongoing research.   Most experts counsel women that clearing of detectable HPV means that those persons are unlikely to transmit their infections to others and they are at very low risk for progression to pre-malignant cytological changes."  This remains the case.

In the interval since m ylast reply I have also discussed your questions with other experts.  They agree that your questions touch on a subject on ongoing research, and debate.  I am not a HPV molecular biologist and your questions go in that direction.  My sense is that while you raise academically interesting and as yet unressolved questions, the answers you seek are beyond the mission of this Forum which is to provide clinical information to our clients as well as questions beyond my level of expertise.  I have little more to offer to you. 

As you know, we provide up to three responses to each client.  This is my 3rd response.  Thus this thread will be closed shortly without further replies.  I will add in closing that I worry that, as at least implied above, you are overly concerned over the possiblity of recurrence of your previously cleared HPV infection.  I suspect that if this the case, these concerns are misdirected and a distraction and would urge you to instead follow guidelines for regular follow-up, a practice which would serve you well and is ov proven benefit to women with past HPV infections.  Take care.  EWH

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Understood. Thank you. I may purchase a second question for a quick clarification on that last point. I am good for now. Thanks!