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TWiV 135 Letters

Michael writes:

I had previously wondered why the technology discussed on episode “Barking Up the Right Tre” (in which an engineered recombinase has been shown to remove HIV from the genome) couldn’t be similarly used in HPV. I know that a Cre has been used to integrate HPV into cells. However, when I asked Prof. Silverstein about this technology, he indicated that HPV doesn’t integrate predictably and that there is limited clonal expansion. Can you please explain how this virus infects cells so reliably in the transition zone between the endocervix and ectocervix and yet a recombinase cannot be targeted to these (assuming you could get the Cre into the cell, which I realize is maybe the hardest part for both Tre and Cre)???

Additionally, is it fair to think that HPV in cervical cancer is analogous to APC in colon cancer, in that they both set off the steps necessary for tumor growth? Is there any commonality with the other steps (myc? B-raf? K-ras) seen in cervical cancer and/or any order in these changes? Obviously it’s a tough question – how would one even go about trying to understand the order of events if he wanted to know?

Finally, are there any interventions to block E6 and E7 after infection and before tumorigenesis?

Thomas writes:


I am a pediatrician in Stoughton, WI and love your show and share your passion for educating "the masses" in whatever corner of the world you are in. Thanks for what you do. I am also passionate about immunizations and would like to clarify some of the points in your recent podcast on HPV (which I thoroughly enjoyed).

1. Pap smears are not routinely recommended at initiation of sexual activity primarily because most adolescent HPV is cleared spontaneously (though we don't know why). Due to this fact, it has recently been stated by several medical governing bodies that Pap smears do not need to start until females are 21 yrs old.

2. HPV typing is not recommended routinely along with Pap smears for most practices. It is quite a bit more costly than a Pap smear, so what some practices do is if the Pap smear is abnormal, they reflex that specimen to HPV typing. Even HPV typing is not specific because it is a panel of HPV types that includes (I think 13 of ) the most common cancer causing types of HPV (it does include 16 and 18). So, if the reflex HPV testing is positive, that person may get more frequent follow up, if reflex HPV testing is negative they may space out the repeat Pap smear testing.

Hope this helps.

Keep up the good work and the bad jokes.

Thomas Murwin, MD, FAAP

Pediatrics and Adolescent Medicine

Dean Clinic Stoughton

Stoughton, WI

Mark writes:

Hello Vincent and other hosts,

Recurring themes on TWiV are public suspicion against vaccination, decline of infant vaccination, and broader societal effects. I recently heard TWiV #132 wherein you (i.e. third person, plural) speculated that lack of direct or familial awareness of common, preventable diseases is a factor leading to decline in vaccination.

As a listener pick of the week, I nominate the site shotbyshot.org -- it has video case studies from people talking about how lack of vaccination hurt family members, friends, or patients who contracted preventable diseases. Take a look. The videos are well done. Be forewarned, many of them are heart breaking.

How did I discover this site? I recently received my decennial booster shot for tetatnus. The administering nurse said that California has an epidemic of pertussis, aka whooping cough. I was given Tdap, a cocktail against tetatus, diptheria, and pertussis. Question about terminology: is it correct to call a vaccination like this, or MMR, trivalent? Or does the term trivalent instead refer to a medicine with three different vaccines in it against a single disease?

I had long thought whooping cough is one of those diseases that scared your parents, and which you never encounter because everyone got vaccinated for it in childhood. I was surprised that it was epidemic here in California -- reported cases have increased 100x in the past few years. This is not a California-only issue, there are epidemics in Michigian, Ohio, Florida among other states. Interested listeners can check the CDC's MMWR report. Here is a link to the PDF for the period ending 5/1/11: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6017md.htm?s_cid=mm6017md_w -- open it and search for pertussis in Table II. You will find regional and state level reporting.

Via Google I found that California's State Legislature added "personal belief" as a reason for exemption from mandatory vaccination. Opinion and myth trump science. The only comment I will make on California's elected officials and their policy is that they mandate a higher level of care my cocker spaniels, via mandatory vaccinations against rabies and other disease, than is required for school age children. Maybe this is why some call California the "epicenter of the anti-vaccine movement."

Keep up the good work with all three of your podcasts. Please, before launching another podcast, invent the 25 hour day to help listeners find time for all your great content.



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