Are the HPV strains Gardasil protects against antagonistic to other high risk HPV strains?

[mhatrw]

Gardasil confers protection against low risk HPV strains 6 & 11 (associated with genital warts) and high risk HPV strains 16 & 18 (associated with cervical cancer). But if any of these four strains of HPV are antagonistic to any of the other thirteen high risk strains of HPV other than 16 & 18 (all thirteen of which are also associated with cervical cancer), then Gardasil could actually end up increasing the overall prevalence of cervical cancer when the results of Gardasil's promised but currently completely unproven "efficacy" against cervical cancer finally become clear some 30+ years from now.

Some recent medical studies appeabr to indicate that this may in fact be the case:

http://vir.sgmjournals.org/cgi/content/full/80/11/2931

It is not well-established whether the different HPV types interfere with infection or pathogenesis by each other. Possible interactions in cervical carcinogenesis between infection with the most common HPV types (6, 11, 16, 18 and 33) were studied in a seroepidemiological case- control study of 218 women with primary untreated cervical cancer and 219 healthy age-matched control women. As previously shown, HPV-16 seropositivity was associated with cervical cancer risk , but HPV-16 was not associated with cervical cancer risk among HPV-6 seropositive women (OR, 1·0). The relative excess risk due to interaction between HPV-6 and -16 was -2·35 (95% confidence interval, -0·04 to -4·65), indicating significant antagonism. The results suggest that infection with HPV-6 may interfere with HPV-16-associated cervical carcinogenesis.

http://content.nejm.org/cgi/content/full/356/19/1991

In contrast to a plateau in the incidence of disease related to HPV types 16 and 18 among vaccinated women, the overall disease incidence regardless of HPV type continued to increase, raising the possibility that other oncogenic HPV types eventually filled the biologic niche left behind after the elimination of HPV types 16 and 18.

[varkam]

1. Note that in your second link, that difference is described as non-significant...

shortly after where you stopped quoting.

[Hannah Bell]

5. ...

"An interim analysis of vaccine trial data submitted to the FDA11 showed a disproportionate, but not statistically significant, number of cases of grade 2 or 3 cervical intraepithelial neoplasia related to nonvaccine HPV types among vaccinated women. Updated analyses of data from these ongoing trials will be important to determine the effect of vaccination on rates of preinvasive lesions caused by nonvaccine HPV types."


actual significance would be time-dependent; the final incidence of non-16/18 lesions & cancers would take many years to emerge.

the interim results simply raise the question: are "suggestive".

[varkam]

60. It merely raises a possibility, nothing more.

It is insufficient to be able to claim anything, one way or the other, for the time being.

[mhatrw]

74. That's the whole point.

Thus the same can be said for Gardasil's efficacy against cervical cancer.

[varkam]

117. Not exactly. eom

[WillYourVoteBCounted]

100. Unscientific and offensive to Merck!

Stop being such a prude!

[varkam]

118. I don't even know what you're trying to say. eom

[trotsky]

2. "recent medical studies"

1999 is recent? :shrug:

[Hannah Bell]

6. ...

"HPV-16 was not associated with cervical cancer risk among HPV-6 seropositive women (OR, 1·0). The relative excess risk due to interaction between HPV-6 and -16 was -2·35 (95% confidence interval, -0·04 to -4·65), indicating significant antagonism. The results suggest that infection with HPV-6 may interfere with HPV-16-associated cervical carcinogenesis."

significant antagonism

[trotsky]

9. 1999 is recent?

Talk about antagonism.

[mhatrw]

11. This is all you have?

That's pretty pathetic.

[trotsky]

12. I'm just asking.

What's your cutoff for something being considered "recent"?

[mhatrw]

14. Do you really have to pick a nit with a single adjective I used?

What's you cutoff for something considered "recent"? Mine is in the last 10 years.

The fact that one of the studies showing antagonism was done in 1999 only makes the questions more pressing. Why didn't the FDA require Merck to demonstrate that there is no significant antagonism between the HPV strains Gardasil protects against and other high risk HPV strains before approving Gardasil?

Note that in Gardasil's clinical trials Merck has collected a lot of data that could be used help evaluate the relative antagonism levels of different HPV strains to one another. Yet Merck has chosen not to release that data. Why not?

[trotsky]

15. Well, it's more than just an adjective.

Although it's important in this discussion, since in 1999 I don't know how many HPV researchers were aware of vaccination work.

But see post #13.

[mhatrw]

17. How about answering the questions? n/t

[trotsky]

22. Just did. Have fun. n/t

[mhatrw]

24. The study showed that getting HPV 6 confers protection against

cervical cancer associated with a high risk HPV strain (16). Gardasil confers protection against HPV 6. How is this a good thing for Gardasil?

[trotsky]

28. See post #26

and pick a subthread you want to continue this on.

[mhatrw]

56. I'd like to continue this discussion to the ends of the earth.

You, on the other hand, want to stay so ignorant about microbial antagonism that you can declare your failure of comprehension to be a glorious victory for the forces of Merck.

[trotsky]

58. See post #57.

I can keep this up as long as you want. OK, well until I feel like having a beer and going to bed.

[WillYourVoteBCounted]

98. Plse don't criticize Merck products, they need the money to pay off the Vioxx Victims

where else can they get a few billion $

And any how, after they pay off the Vioxx victims, they can rush some other
miracle drug onto the market to pay the Gardasil victims.

[Hannah Bell]

18. 1999 is less than 10 years ago, recent enough in terms of research adequacy.

http://vir.sgmjournals.org/cgi/content/full/80/11/2931

The study is from the Journal of Virology. It's case-controlled (comparison group),
~440 subjects.

"The relative excess risk due to interaction between HPV-6 and -16 was -2·35 (95% confidence interval, -0·04 to -4·65), indicating significant antagonism. The results suggest that infection with HPV-6 may interfere with HPV-16-associated cervical carcinogenesis."

It's not clear why you focus on the loose use of the word "recent" in the OP & ignore the research.

[trotsky]

31. I hereby rescind my comment about it not being recent enough.

I like this study! :)

The results suggest that infection with HPV-6 may interfere with HPV-16-associated cervical carcinogenesis.

Yup, infection with HPV-6 helps PREVENT the cancer normally caused by HPV-16.

Garadasil protects against 6 *and* 16, as well as 11 and 18. The results of this study indicate that Gardasil may just help reduce cancer caused by the strains it doesn't immunize against.

So thanks for popping this thread back up and making me read it more closely! :hi:

[cosmik debris]

32. That's what happens when one is blinded by obsession

It's sorta funny really.

[trotsky]

33. When it happens again and and again and again...

that someone posts studies or articles or interviews that actually contradict the point they're trying to make...

well, you just gotta wonder.

[Hannah Bell]

113. no, the point is that there's interaction: & more than 40-70 types of hpv.

[Hannah Bell]

114. you've not recognized the point i wish to make because you're focused on a simpler one:

v6 has been determined to interact with 16, gardasil knocks out both, no problem.


My interest is in the finding of interaction itself, which opens many cans of worms, e.g.:


"In contrast to a plateau in the incidence of disease related to HPV types 16 and 18 among vaccinated women, the overall disease incidence regardless of HPV type continued to increase, raising the possibility that other oncogenic HPV types eventually filled the biologic niche left behind after the elimination of HPV types 16 and 18.

An interim analysis of vaccine trial data submitted to the FDA11 showed a disproportionate, but not statistically significant, number of cases of grade 2 or 3 cervical intraepithelial neoplasia related to nonvaccine HPV types among vaccinated women."


Or:

1: Am J Surg Pathol. 2008 Jul;32(7):1044-50.Links
Basaloid squamous cell carcinoma of the head and neck is a mixed variant that can be further resolved by HPV status.

Basaloid squamous cell carcinoma (BSCC) of the head and neck is set apart as a distinct subtype of squamous cell carcinoma.

The absence of HPV16 was significantly associated with decreased overall survival even though patients with HPV16-positive carcinomas were more likely to present with lymph nodes metastases.

HPV16-positivity in squamous cell carcinomas of the head and neck is now recognized as a powerful indicator of improved patient survival.



There are more than 40-70 hpv, more than 15 identified as oncogenes, & not only for cervical cancer. Presence of virus is not identical to presence of antibodies.

The significance of the paper was it demonstrated interaction between hpv variants affecting cancer incidence in humans, something that was only hypothetical not too many years before.

One instance which implies others.

[trotsky]

128. But this instance actually shows a BENEFICIAL effect.

Previous infection by HPV-6 lessened the chance of cancer. That's a good thing, right?

[Hannah Bell]

133. sure, if you don't mind penis warts. but with hpv 33, the interaction

is opposite, according to the paper.

there are theoretically infinite interactions, synergistic & antagonistic, not only with cc, but with other cancers.

[trotsky]

135. I'm going to take a wild guess here and suppose that not many women get penis warts.

I'm no expert, but hey.

[Hannah Bell]

140. i'm going to take a wild guess & suppose that the antagonism

between 6 & 16 operates in men as well & that hpv 16 is associated with penile cancers.

how 'bout that, i'm right!

http://www.ncbi.nlm.nih.gov/pubmed/17764110

[trotsky]

142. So have there been any studies showing that like in women,

HPV-6 infection reduces the risk of cancer caused by HPV-16?

Oh and please try to use the terminology correctly. HPV-6 is not antagonistic toward HPV-16, it's antagonistic toward carcinogenesis caused by HPV-16. There's a difference.

[Hannah Bell]

144. no, you're the one using the terms wrong. it's viral antagonism, virus to virus

interaction, not virus to cancer interaction, so far as is known. which is very little.

the viruses are antagonistic (or synergistic, or other things) to each other, e.g. by shutting off expression of virus protein products.

the reduced (or enhanced) carcinogenesis is a by-product of that.

you're just making stuff up, & it's pretty obvious.

[Hannah Bell]

145. Here's a v-to-v example:

http://www.pubmedcentral.nih.gov/articlerender.fcgi?art...

"Mutual functional antagonism of the simian virus 40 T antigen and the hepatitis B virus trans activator."


"It has been shown previously that the simian virus 40 early-region gene products (large-T and small-t antigens) prevent trans activation by pX (Hep B virus protein).

Furthermore, pX in turn interferes with two of the known functions of T antigen, transcriptional trans activation and simian virus 40 DNA replication.

We propose that pX and T antigen inactivate each other by forming a nonfunctional complex in vivo."


So: SIV-40 virus & HepB virus are mutually antagonistic. They each prevent expression of proteins made by the other, which blocks replication a/or transcription.

Thus, likelihood of no cancer, despite exposure to the virus & production of antibodies.



It's not a response of the body to viruses, or of viruses to cancer. It's a response of viruses to each other, & the types & variations are theoretically infinite.

Which is why some posters' simple "ha, ha, gardasil takes care of 6 AND 16!!!" comments are so funny.

[trotsky]

147. From the OP:

The results suggest that infection with HPV-6 may interfere with HPV-16-associated cervical carcinogenesis.

Not "HPV-6 may interfere with HPV-16" but "*infection* with HPV-6 may interfere with HPV-16-associated CARCINOGENESIS"

I'm not the one making stuff up here. Sorry.

[Hannah Bell]

148. from your original claim:

"Oh and please try to use the terminology correctly. HPV-6 is not antagonistic toward HPV-16, it's antagonistic toward carcinogenesis caused by HPV-16. There's a difference"


yes, there's also a difference between "antagonize" & "interfere."

you're just making stuff up as you go, like i said.

[trotsky]

152. So you admit you were stating it incorrectly?

Or are you more intent on just focusing on me?

[mhatrw]

155. How else could HPV strain antagonism possibly be measured other than

by the effect of the seropositivity of one strain on the visible clinical manifestations of another strain?

[Hannah Bell]

159. so you admit you just make it up as you go?

it's becoming pretty obvious.

[trotsky]

160. Sorry, but you haven't answered the questions.

You just keep throwing accusations at me. Consistent pattern. Please let me know when you want to participate in a civil discussion.

[Fire_Medic_Dave]

168. So how is that measured?

How would you measure the antagonism of HPV-6 and HPV-16?

David

[Name removed]

115. Deleted message

Message removed by moderator. Click here to review the message board rules.

[trotsky]

129. Not arguing that, since that's your strawman.

When you know how to use a term, let me know.

[mhatrw]

39. By what mechanism are you proposing that getting infected

with HPV-6 is reducing HPV-16's ability to cause cancer? Do you even understand the issue or are just joining in the tag team out of habit?

[trotsky]

44. That's not my job.

The study you posted showed that it happens. Thanks for the help!

[mhatrw]

49. Yes, the study shows that HPV-6 interferes with HPV-16's ability

to form cancerous dysplasias. Now explain why this good for Gardasil.

[trotsky]

53. I'll do it one more time.

Your argument was that Gardasil could make infections by other HPV strains worse. But you misinterpreted the study you posted, thinking "antagonize" meant that it made the other infection worse. But it didn't - it instead did the opposite, and made it more difficult for the other strain to cause cancer. So you yourself posted evidence that instead says immunity to one strain of HPV helps lessen the damaging effects of another strain.

So it's quite reasonable to believe that immunity from the 4 strains in Gardasil might just as well lessen the damaging effects from other strains! After all, it's been shown before! Thanks to YOU! :hi:

[mhatrw]

55. WTF are you talking about? The most common way that a microbe

antagonizes another microbe is simple ecological interference. Have you ever taken a single course in microbiology?

Google "microbial antagonism" and choke on your extreme ignorance.

[trotsky]

57. I do not think that term means what you think it means.

http://www.online-medical-dictionary.org/Microbial+Antagonism.asp?q=Microbial+Antagonism
Microbial Antagonism
A property of microorganisms which enables one microorganism to kill, injure, or inhibit the growth of a different microorganism.

HPV-6 doesn't kill, injure, or inhibit the growth of HPV-16.

A woman's IMMUNE SYSTEM, after fighting off HPV-6, is evidently able to fight HPV-16 more easily and effectively. Similar to how an infection with mild cowpox provided immunity to the deadly smallpox. Cowpox didn't kill the smallpox virus, it trained the immune system to recognize it more readily and mount a defense before it gained a more significant foothold.

But if name-calling is all you have...

[beam me up scottie]

59. !

[mhatrw]

62. Exactly. Contradicting the Medical Dictionary is an amazing volley!

Dyslexia is a terrible thing.

[mhatrw]

61. So the Medical Dictionary is wrong and you are right! LOL!

I do not think that term means what you think it means.

Correction. You do not think the term means what the Medical Dictionary says it means. You are overruling the Medical Dictionary based on your own misunderstanding of what you thought microbial antagonism was. Microbial antagonism has nothing to do with one's immune system. It has to do with microbes antagonizing each other.

[beam me up scottie]

64. Sad.

tsk.

[mhatrw]

66. Your understanding of the issues here and the insight you offer are

stunning. Thanks you for contributing so substantively to so many discussions on this forum.

[beam me up scottie]

67. Get back to me when you can prove your claims.

I've bookmarked them, btw, so expect me to ask for proof every time you post your assumptions. :hi:

[mhatrw]

68. Is that a threat? n/t

[beam me up scottie]

69. Nope, you're not that special. I expect everyone to be able to prove their absurd claims.

Get back to me with that evidence when you find some, 'kay?

[mhatrw]

70. What evidence for what?

[beam me up scottie]

71. This absurd claim in particular:

Gardasil's advocates are practicing faith-based medicine. They have faith that Gardasil is extremely safe, and they have faith that the protection Gardasil confers against HPV 16 & 18 will translate into significant protection against cervical cancer some 30+ years down the line. On the other hand, they have no faith that there will be advances in HPV testing or cervical cancer treatments over the next 30 years that will render Gardasil's at best partial protection against an ever reducing threat obsolete.

But I can cite any of the others you've been posting too.

[mhatrw]

72. Please desist stalking me.

Do not "stalk" another member from one discussion thread to another. Do not follow someone into another thread to try to continue a disagreement you had elsewhere. DU's Rules

[beam me up scottie]

76. You've been double posting in two threads, your claims are fair game.

Of course, once you prove them I'll go away.

[mhatrw]

77. As I said, I cannot prove that Gardasil advocates are not evil people.

That is an assumption I am making.

[Name removed]

79. Deleted message

Message removed by moderator. Click here to review the message board rules.

[varkam]

120. Jesus H. Tapdancing Christ.

:rofl:

[WillYourVoteBCounted]

99. Lets here this cheer again, haven't heard it for awhile - Oh VAERS! Oh Prude! Oh Poor Merck!

[trotsky]

124. Oh dear.

I really wanted to let you save face and bow out gracefully, but this post is just too much.

YOU used the term microbial antagonism, but the situation you are describing is NOT that.

I'm not saying the dictionary is wrong, I'm saying YOU are wrong because you are using the term incorrectly.

[mhatrw]

125. Please explain the most common mechanism of viral to viral antagonism to us.

This should be good.

I've told you over and over that the most common mechanism of antagonism among BOTH microbes and viruses is simple interference.

Let's see what the authors of the paper in question have to say:

"The cervical cancer risk for one HPV type when all other viruses are negative was considerably higher for HPV-16, but lower for HPV-33."

"...the fact that the antagonism with HPV-16 was only seen with HPV-6 suggests a substantial type-specific component of the HPV-6 antibody response."

"It is conceivable that antagonism between seropositivity to two papillomaviruses in cervical cancer might be at the level of the antibody response rather than on the infection itself, i.e. that among women with cancer (but not among controls), the presence of antibodies against HPV-6 would antagonize the ability to mount an immune response to HPV-16."

"However, there was no evidence of such impairment of antibody responsiveness. As can be seen in Table 4(a), among cases and among controls an identical proportion (43%) of HPV-6- positive subjects were also HPV-16-seropositive."

"A tendency to antagonistic interactions was also observed in another virus combination: HPV-16 and -18. The possibility that some of the risk associated with HPV-16 or -18 is attributable to confounding by co-variation with the other type is not likely, since the cancer risks observed when positives for the other type were excluded were similar or greater than the crude risks, suggesting that the antagonism does reflect a biological interference."

"The present study has investigated only five common types of HPV. Taking into account the large number of HPV types, it is likely that more comprehensive studies of more HPV types may reveal various additional interferences between them. Considering the fact that virus interferences may be of relevance for understanding of HPV-induced carcinogenesis and for design and evaluation of vaccines, such studies seem warranted."

Isn't it time for you to simply admit you were wrong?

[trotsky]

127. "Isn't it time for you to simply admit you were wrong?"

Not when you're the one who was, silly!

[mhatrw]

132. Please explain the most common mechanism of viral to viral antagonism to us, then.

If it is not simple interference, then what is it?

[trotsky]

137. Why? It has no relevance on what I've said.

But I will note that you have corrected your use of terminology, so I'll take that as your long-overdue admission of error. Well done!

[mhatrw]

139. OK, so once you lose an argument "It has no relevance."

Gotcha!

[trotsky]

141. If this is what you need to finally be at peace and stop insulting me,

so be it. At least you're using the correct terminology now.

[Hannah Bell]

150. that person will never admit he's wrong. he's not interested in the question.

he's interested in giving you a hard time.

he just makes stuff up.

in fact, there are several folks like that here.

[Fire_Medic_Dave]

170. You said microbial antagonism.

Revealing that you didn't know that a virus wasn't a microorganism until I pointed it out to you yesterday.

David

[Hannah Bell]

116. Assumption of generalized "training" is contradicted by the fact

that there wasn't any such general effect with other variants studied, e.g.:

"The cervical cancer risk for one HPV type when all other viruses are negative was considerably higher for HPV-16, but lower for HPV-33."


The authors say:

"The serum antibody response to HPV capsids is established to BE HPV-type-specific, except for HPV-6 and -11 capsids that contain both type- specific epitopes and epitopes shared between HPV-6 and -11 (Christensen et al., 1996)."

"Cross-reactivity between HPV-6 and -11 may be the reason why very few subjects were HPV-11-positive in the absence of seropositivity to other HPV types."

"On the other hand, the fact that the antagonism with HPV-16 was only seen with HPV-6 suggests a substantial type-specific component of the HPV-6 antibody response."

"It is conceivable that antagonism between seropositivity to two papillomaviruses in cervical cancer might be at the level of the antibody response rather than on the infection itself, i.e. that among women with cancer (but not among controls), the presence of antibodies against HPV-6 would antagonize the ability to mount an immune response to HPV-16."

"However, there was no evidence of such impairment of antibody responsiveness. As can be seen in Table 4(a), among cases and among controls an identical proportion (43%) of HPV-6- positive subjects were also HPV-16-seropositive."

"A tendency to antagonistic interactions was also observed in another virus combination: HPV-16 and -18. The possibility that some of the risk associated with HPV-16 or -18 is attributable to confounding by co-variation with the other type is not likely, since the cancer risks observed when positives for the other type were excluded were similar or greater than the crude risks, suggesting that the antagonism does reflect a biological interference."

"This is in contrast to the results obtained regarding HPV-33."

"This virus is categorized as a moderately carcinogenic virus, since it is rather uncommonly found in invasive cancer tissue. Although HPV-33 seropositivity is strongly related to cervical cancer risk, HPV-33 positivity had no association with cervical cancer when subjects seropositive to other HPV types were excluded from analysis."

"This suggests that the risk associated with HPV-33 seropositivity is attributable to confounding by other HPV types."

"The observed tendency for a synergistic interaction between HPV-33 and HPV-16 was not statistically significant."

"The present study has investigated only five common types of HPV. Taking into account the large number of HPV types, it is likely that more comprehensive studies of more HPV types may reveal various additional interferences between them. Considering the fact that virus interferences may be of relevance for understanding of HPV-induced carcinogenesis and for design and evaluation of vaccines, such studies seem warranted."

[mhatrw]

122. But who cares what the authors say or what the medical dictionary says.

Gardasillies have an incontrovertible faith that HPV antagonism must be good news for Gardasil!

[Name removed]

37. Deleted message

Message removed by moderator. Click here to review the message board rules.

[trotsky]

43. I am perfectly willing to admit when I was wrong.

Are you??? :rofl:

[mhatrw]

48. But you aren't willing to answer simple questions.

What kind of antagonism did you think I was talking about other than interference? Explain yourself.

[trotsky]

51. LOL

Keep kicking. There are no questions I need to answer. You've answered them all for me. :)

[Name removed]

54. Deleted message

Message removed by moderator. Click here to review the message board rules.

[mhatrw]

65. LOL!

The fact that you know think your own "understanding" of microbial antagonism supersedes the Medical Dictionary tells us all we need to know about your level of expertise concerning this issue.

[Hannah Bell]

104. The significant point is the demonstration of interaction. There are more than 40 HPV.

This study was one of the first to show interaction between types in humans.

But you said the work was too old, so I guess it's irrelevant.

[Hannah Bell]

106. Ecologically, we'd expect the least deadly viri to colonize most niches.

The more deadly/quicker killers to be least prevalent, because they kill their hosts quicker.

So v6 antagonizes/mitigates v16.

And if v16 mitigates something worse?

This study confirms interaction, which opens up another can of worms.

Most cervical cancers are highly treatable, comparatively non-aggressive.

Most cervical cancers are associated with 16.

18 is thought to cause more aggressive cancers.

there are 40 more.

[mhatrw]

107. Here's the thing. Merck has the beginnings of the answer to these questions.

All of the Gardasil/control subjects have been given regular HPV tests all along the way, so Merck currently has the largest repository of HPV interaction data ever gathered on file -- and they have been withholding this information from the greater scientific community. Kinda makes you wonder what Merck's initial results are showing, doesn't it?

[Hannah Bell]

111. Further interesting points:

HPV is associated with other cancers.

1: Am J Surg Pathol. 2008 Jul;32(7):1044-50.

Basaloid squamous cell carcinoma of the head and neck is a mixed variant that can be further resolved by HPV status.

Basaloid squamous cell carcinoma (BSCC) of the head and neck is set apart as a distinct subtype of squamous cell carcinoma on the basis of its basaloid appearance and aggressive behavior. The purpose of this study was to determine whether BSCC could be further subdivided on the basis of human papillomavirus 16 (HPV16) status.

HPV16 was detected in 16 of 21 (76%) BSCCs of the oropharynx, but in only 2 of 32 (6%) BSCCs from nonoropharyngeal sites (P<0.0001, Fisher exact).

The absence of HPV16 was significantly associated with decreased overall survival (Hazard ratio=17.1; 95% confidence interval=7.2-40.3, log-rank P=0.0001), even though patients with HPV16-positive carcinomas were more likely to present with lymph nodes metastases (P=0.01, Fisher exact).

HPV16-positivity in squamous cell carcinomas of the head and neck is now recognized as a powerful indicator of improved patient survival. HPV16 detection thus permits resolution of a less aggressive component within a high-grade subtype of head and neck carcinoma.



So what will the effect of HPV vaccination be for other cancers....who knows?

We don't even understand the interactions.

[cosmik debris]

3. From your own link:

...the vaccine has high efficacy against certain HPV types that cause life-threatening disease, and it appears to be safe; delaying vaccination may mean that many women will miss an opportunity for long-lasting protection.

Within both trials, subgroups of subjects with no evidence of previous exposure to relevant vaccine HPV types were evaluated separately for vaccine efficacy. In these subgroups, efficacy of nearly 100% against all grades of cervical intraepithelial neoplasia and adenocarcinoma in situ related to vaccine HPV types was reported in both trials.

Gardasil is safe and effective according to your own sources.

But your superstitious fear and hatred have blinded you to even YOUR OWN references.

[mhatrw]

8. Gardasil "appears" to be safe and it was to be effective against HPV 6, 11, 16 & 18.

among the subgroup of women who had never been previously exposed to these HPV strains. But that doesn't mean that it is effective against cervical cancer. That's what my entire OP is about. Do you have the ability to understand the difference between being effective in offering protection against 4 HPV strains and being effective against cervical cancer?

[Celebration]

4. new NEJM editorial gives voice to these very concerns

http://www.democraticunderground.com/discuss/duboard.php?az=show_mesg&forum=222&topic_id=41870&mesg_id=41893

[WillYourVoteBCounted]

7. Maybe. Could be like killing one bacteria makes another stronger

anything is possible but we won't know until lots of studies are done.

But hey, there's an emergency, we have a massive outbreak.

[mhatrw]

10. What is particularly disturbing about this is that Merck has a lot of data that

could shed light on the level of antagonism of different HPV strains to one another and for some reason they have chosen not to release this data.

[trotsky]

13. Hmm, since Gardasil is effective against 6, 11, 16, AND 18...

Your first article, 9 years old, doesn't really apply, does it?

[mhatrw]

16. It shows that a very common HPV strain associated with genital warts

is antagonistic to a less common strain associated with cervical cancer. What makes you think that a larger and more comprehensive study would not demonstrate HPV 6's antagonism to other high risk HPV strains? Surely you understand why this might be case. Surely you understand why it would take a larger study (the studies Merck conducted to get Gardasil approved would be a good start except for the fact that Merck is withholding this data) to confirm the relative antagonism levels of HPV 6, 11, 16 and 18 to other high risk HPV strains.

[trotsky]

20. OK, you're wrong on two counts.

And granted, I could be completely wrong, BUT...

#1, Gardasil protects against strains 6 AND 16. So any worries about one causing problems with the other wouldn't really apply here, would they?

#2, I would really invite you to re-read the TITLE of the first study.

Serological evidence for protection by human papillomavirus (HPV) type 6 infection against HPV type 16 cervical carcinogenesis

In other words, infection first by HPV-6 results in a *decrease* in carcinogenesis if later infected by HPV-16.

This is confirmed in the Results section:

An increased HPV-16-associated risk was mainly seen when HPV-6-positive subjects were excluded...

Again, cancer risk from infection by HPV-16 DECREASED when HPV-6 was a previous infection. All this talk about antagonism is referring to HPV-6 being antagonistic toward CARCINOGENESIS. I.e., it prevents cancer.

So in your continuing zeal to take down Gardasil, you just provided more evidence that it's a GOOD THING.

Nice job! :thumbsup:

[mhatrw]

23. The study showed that the sub-group that tested positive

for HPV 6 (a low risk strain Gardasil protests against) as well as HPV 16 (a cancer risk strain Gardasil protects against) showed a far lower incidence of cancer associated with HPV 16 than the group that tested positive for HPV 16 but not HPV 6. Read the methods and results.

If getting HPV 6 reduces your chances to get cancer, how does that make Gardasil's protection against HPV 6 a good thing?

[trotsky]

26. Because it protects against 6 *and* 16.

The article which you so delightedly posted, thinking it supports the case against Gardasil, actually supports it by showing that immunity against one strain lessens the chance of a carcinogenic strain from causing cancer.

In other words, the same mechanism by which 6 guards against 16, the 4 strains that Gardasil prevents may lessen the chance of getting cancer from any of the others that cause it!

So again, thanks for the link!

[mhatrw]

29. Not if the mechanism is simple interference.

Think.

[trotsky]

30. Interference with the OTHER strain's ability to cause cancer!

YOU need to think!

The very study that YOU posted further strengthens the case FOR Gardasil. I am truly glad you're on that side of the argument, you're helping the case for Gardasil far more than you're hurting it.

[mhatrw]

34. Yes. Interference with the strength of HPV 16.

What is your problem?

[trotsky]

35. Not my problem. Yours.

For posting a study that ruins your own argument.

You thought it said HPV-6 antagonizes HPV-16, but it actually antagonizes HPV-16's ability to cause cancer.

Game, set, and match.

[mhatrw]

36. Yes, because HPV-6 interferes with HPV-16's ability to cause a dysplasia.

What about this is confusing to you?

[trotsky]

38. Nothing at all!

Please keep kicking this thread, it will be good for others to see how wrong you were.

[mhatrw]

40. By what mechanism other than interference are you proposing that

getting infected with HPV-6 reduces your chances to get cervical cancer associated with HPV-16? How can this possibly be a boon for Gardasil? Please explain.

What kind of antagonism did you think I was talking about other than simple interference? Please explain. Have you ever taken a single course in microbiology?

[trotsky]

42. Keep kicking!

More exposure!

[mhatrw]

45. Keep avoiding the questions, thus confirming your ignorance. n/t

[trotsky]

47. Keep kicking!

Thanks!

[mhatrw]

50. OK! n/t

[Fire_Medic_Dave]

73. Are you saying that HPV-6 itself is weakening the HPV-16?

[mhatrw]

78. That is what antagonism is. n/t

[Fire_Medic_Dave]

81. Is it attacking or is it crowding it out?

[mhatrw]

83. Either or both. n/t

[Fire_Medic_Dave]

82. What type of antagonism is this?

[mhatrw]

84. I don't know. But simple ecological interference is the simplest explanation.

[Fire_Medic_Dave]

85. You've been going on and on about microbial antagonism.

Now you don't know. You have been going off on varkam asking if he has ever taken a microbiology class in every response. So if you have had a microbiology class then you would know that most scientist don't consider viruses to be microorganisms. Viruses are often classified as non living. So I think your microbial antagonist explanation, is based on living organisms competing for survival. Viral antagonism is a much different beast, google viral antagonism and come back and tell me if you think it's still that simple.

David

[mhatrw]

87. You misunderstood what I meant.

So you think that the definition of antagonism suddenly changes when we go from microbes to viruses? Really?

What I was saying was that antagonism generally means crowding out, but that certain organisms have other methods of antagonizing their competitors such as biochemical inhibitors. The experiment in question offered no evidence to determine if the antagonism demonstrated was strictly due to interference or not, so I can't say for sure that HPV-6 does not have some other defense against HPV-16 besides crowding it out. Antagonism between two competing self-replicating entities is a well-defined and understood concept throughout biology. The same conceptual definition is even used in pharmacology to refer to chemicals that crowd out other chemicals. The definition doesn't suddenly change on the viral level.

[Fire_Medic_Dave]

89. I don't think so.

A virus isn't a microbe. Bacterial infections and viral infections are 2 completely different things and attack the body in completely different ways. The body reacts differently to viruses than it does to bacteria. That's why we treat viral and bacterial infections differently. To say that the bodies response to viruses and bacteria is the same is simply wrong.

David

[mhatrw]

92. You are just making things up to suit yourself.

A virus isn't a microbe. Bacterial infections and viral infections are 2 completely different things and attack the body in completely different ways. The body reacts differently to viruses than it does to bacteria. That's why we treat viral and bacterial infections differently. To say that the bodies response to viruses and bacteria is the same is simply wrong.

Agreed on all points. But none of this has anything to do with the correct definition of virus to virus antagonism.

Read this: http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.mi.05.100151.001455

Again, just because viruses are not microbes doesn't mean that concept of viral antagonism is completely different from the concept of microbial antagonism. That wouldn't make much sense, would it? Wouldn't scientists just use a different phrase, you know, like "generates antibodies" or "confers resistance" or "provides immunity" rather than "antagonism"?

[Fire_Medic_Dave]

93. I'm saying that given the bodies response to viruses antagonism is to simple an explanation.

There is far too much going on with the adaptive immune system to say that simple virus to virus antagonism is the only thing having an affect.

David

[mhatrw]

97. It's possible. But isn't it more likely that HPV-6 just kicks out HPV-16?

Like it or not, that is the classic case of viral antagonism.

[Fire_Medic_Dave]

101. I would guess it's some combination of immune response and viral antagonism.

The body seems to attack pathogens of any kind in multiple ways. Regardless gardasil protects against both. So it's kind of a mute point as far as HPV-6 and HPV-16 are concerned.

David

[mhatrw]

105. Yes, but you have to understand that other 13 (and counting) high risk HPV strains

could have been ecologically antagonized by any of the four HPV strains Gardasil protects against. This antagonism could have largely accounted for the relative infrequency of these strains being associated with cervical cancer. With four of the most common HPV strains out of the picture, other HPV strains could become more virulent as well as more prevalent. Only Merck has a clue as to the answer to this question and to this point they have withheld the relevant data. Why?

[Fire_Medic_Dave]

162. That's a possibility.

As we have seen with the rise of MRSA. I don't know if Merck has these answers or not, if they do, not releasing the data will put them on the same legal ground they were on with Vioxx.

David

[Hannah Bell]

112. viral evolution

http://en.wikipedia.org/wiki/Viral_evolution

[Fire_Medic_Dave]

167. What about it?

[Hannah Bell]

173. you said:

most scientists "don't consider viruses to be microorganisms. Viruses are often classified as non living."

it's true - but they do things that are analogous (i hope you won't take issue with the word, it's the best i can come up with being exhausted) to living organisms.

viral evolution is an example of something that sort of parallels living processes.

[Fire_Medic_Dave]

175. I never said different.

Some of the characteristics required to be considered a living organism aren't met by some bacteria either but they are still considered living.

[Hannah Bell]

19. It does. It shows statistically significant interaction between 2 types

of hpv. The presumption would thus be that there are further interactions to be discovered.

[trotsky]

21. Yes, that infection by HPV-6 appears to lessen the chance of cancer

commonly caused by HPV-16.

See post #20.

[mhatrw]

25. How is the fact that being infected with HPV 6 helps confer

resistance to cervical cancer a good thing for Gardasil?

[trotsky]

27. Because it protects against 6 *and* 16.

See post #26.

[mhatrw]

41. Are you just here to confuse the issue? If HPV-6 interferes with HPV-16,

what makes you think that it doesn't interfere with other high risk HPV strains?

[trotsky]

46. What makes you think that it will?

After all, this study that you posted showed that infection by one strain lessened the chance of getting cancer from another. What makes you think it will be different for other strains? Please propose a mechanism by which this would happen.

[Name removed]

52. Deleted message

Message removed by moderator. Click here to review the message board rules.

[mhatrw]

63. HPV-6 inhibits HPV-16's ability to cause dysplasias by simple interference.

Google "microbial antagonism."

[Fire_Medic_Dave]

75. Or does HPV-6 exposure strengthen the immune system against HPV-16?

That is more likely what is taking place.

David

[mhatrw]

80. Really? Then why did the researchers describe the relationship as antagonistic?

You do realize that the simplest explanation, by far, is that HPV-6 infections simply crowd out most HPV-16 infections, right? Remember, there was no way to tell who was infected with which strain first in this experiment.

[Fire_Medic_Dave]

86. Viral antagonism is closely related to the immune system, unlike microbial antagonism.

[mhatrw]

88. No, it isn't.

You are misunderstanding whatever led to you believe that. I'm assuming that you read something about the immune system being antagonized by a virus. That is biochemical antagonism, which is a different animal (although the concept of crowding out is similar). The primary mechanism of viral to viral antagonism is simple interference, although there are other ways certain viruses can antagonize another viruses.

Read this:

http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.mi.05.100151.001455

[Fire_Medic_Dave]

90. So the immune system responds to exposure to viruses and bacteria in the exact same way?

[mhatrw]

91. That's not what I said.

Please read the cite I supplied in my last post. It explains what viral antagonism is.

[Fire_Medic_Dave]

94. You posted an article about viruses in plants.

Plants only have an innate immune system, humans have both an innate and an adaptive immune system.

David

[mhatrw]

96. You are really reaching, Viral to viral antagonism typically has nothing

to do with anybody's immune system. If you want to insist otherwise, please find some evidence for your insistence. I would be happy to learn something new.

[Fire_Medic_Dave]

102. I'm reaching, you posted a link about plant viruses.

Here is a link that might help. http://www.jstor.org/pss/50825

David

[mhatrw]

108. That has nothing to do with viral on viral antagonism.

That's about viruses antagonizing T-cells. I figured that you were reading something like this. Find something about viruses antagonizing other viruses.

[Hannah Bell]

130. this is the same paper. it's not about competition between different viruses. its about single

viruses shifting their expression of proteins so t-cells don't respond as effectively to destroy them. the antagonism is t-cell to virus, not virus to virus.


Here's a v-to-v example:

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=240586


"Mutual functional antagonism of the simian virus 40 T antigen and the hepatitis B virus trans activator."

It has been shown previously that the simian virus 40 early-region gene products (large-T and small-t antigens) prevent trans activation by pX (Hep B virus protein).

Furthermore, pX in turn interferes with two of the known functions of T antigen, transcriptional trans activation and simian virus 40 DNA replication.

We propose that pX and T antigen inactivate each other by forming a nonfunctional complex in vivo."


So: (protein products of) SIV-40 virus & HepB virus are mutually antagonistic.

In this case the interference has nothing specific to do with immune response. It's more blocking normal functioning of the viruses. If expression of proteins a/o replication are blocked, the normal sequelae the virus causes (e.g. cancer) don't occur, or occur less.

It's not a response of the body to viruses. It's a response of viruses to each other, & the types & variations are theoretically infinite.

Which is why some of the posters' simple "ha, ha, gardasil takes care of 6 AND 16!!!" comments are so obliviously funny.

[Fire_Medic_Dave]

163. So the immune response doesn't happen until the viruses decide who going to be in charge.

When a virus enters the body an immune response takes place, you can't discount that response completely and say that viral antagonism is the only thing that's happening. That is the point I have been trying to make the whole time, not very effectively apparently.

David

[Fire_Medic_Dave]

103. Here's another.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1688914

[mhatrw]

109. It's the same article and it's the same problem. It is not about viral on viral antagonism. n/t

[Hannah Bell]

126. that article doesn't have anything to do with 1 virus affecting expression of another.

it's bout single viruses evding immune detection.

[Hannah Bell]

121. From the paper:

"The cervical cancer risk for one HPV type when all other viruses are negative was considerably higher for HPV-16, but lower for HPV-33."

"...the fact that the antagonism with HPV-16 was only seen with HPV-6 suggests a substantial type-specific component of the HPV-6 antibody response."

"It is conceivable that antagonism between seropositivity to two papillomaviruses in cervical cancer might be at the level of the antibody response rather than on the infection itself, i.e. that among women with cancer (but not among controls), the presence of antibodies against HPV-6 would antagonize the ability to mount an immune response to HPV-16."

"However, there was no evidence of such impairment of antibody responsiveness. As can be seen in Table 4(a), among cases and among controls an identical proportion (43%) of HPV-6- positive subjects were also HPV-16-seropositive."

"A tendency to antagonistic interactions was also observed in another virus combination: HPV-16 and -18. The possibility that some of the risk associated with HPV-16 or -18 is attributable to confounding by co-variation with the other type is not likely, since the cancer risks observed when positives for the other type were excluded were similar or greater than the crude risks, suggesting that the antagonism does reflect a biological interference."

"This is in contrast to the results obtained regarding HPV-33."

"This virus is categorized as a moderately carcinogenic virus, since it is rather uncommonly found in invasive cancer tissue. Although HPV-33 seropositivity is strongly related to cervical cancer risk, HPV-33 positivity had no association with cervical cancer when subjects seropositive to other HPV types were excluded from analysis."

"This suggests that the risk associated with HPV-33 seropositivity is attributable to confounding by other HPV types."

"The observed tendency for a synergistic interaction between HPV-33 and HPV-16 was not statistically significant."

"The present study has investigated only five common types of HPV. Taking into account the large number of HPV types, it is likely that more comprehensive studies of more HPV types may reveal various additional interferences between them. Considering the fact that virus interferences may be of relevance for understanding of HPV-induced carcinogenesis and for design and evaluation of vaccines, such studies seem warranted."

[mhatrw]

123. Thanks a lot.

Not that I expect what the authors of the paper wrote to have any effect on the blind faith of the Gardasillies...

[Fire_Medic_Dave]

164. Finally we agree.

More studies do seem warranted.

David

[Hannah Bell]

119. The study also found this:

"The cervical cancer risk for one HPV type when all other viruses are negative was considerably higher for HPV-16, but lower for HPV-33."

suggesting other viri act antagonistically on 16, but synergistically on 33.

With 15 known oncogenic hpv, & >40-70 potential ones.

[beam me up scottie]

95. Does it matter that he's citing an article titled 'Interference Phenomena Between Plant Viruses'?

Feed me Seymour, feed me!

[mhatrw]

110. Why not present some evidence of ANY virus on virus antagonism

that has anything to due with the antibodies of any immune system? The classic case of viral antagonism is simple interference.

[Fire_Medic_Dave]

166. Can you show me an example of a virus being introduced to the body without an immune response?

[Hannah Bell]

151. nope, it doesn't. but it does show you don't understand the basics of the topic.

[beam me up scottie]

153. Ah, I forgot what an expert you are. How long have you been working with viruses?

And how many articles regarding this topic have you published?

[Hannah Bell]

156. i;ve worked in a research hospital, & i have a basic knowledge,

such that i can interpret a paper & get what it's saying.

furthermore, i'm WILLING to take the trouble in a discussion to read the papers.

Plant & animal viruses have differences, but the phenomenon of viral interference/antagonism/synergy is broad-brush similar. She posted the paper as an example of that - a general example of the phenomenon.

[beam me up scottie]

158. So you've done research on viruses?

Do tell.

[Fire_Medic_Dave]

165. In what capacity did you work in a research hospital?

Plant and animal viruses have differences and so do plants and animals. Plants do not have an adaptive immune system, humans do.

David

[Fire_Medic_Dave]

177. Why am I not surprised you didn't answer this question?

[mhatrw]

157. How many have you ever read?

Still waiting on the CDC to summarize them for you?

[Fire_Medic_Dave]

169. You have interchangeably used microbial and viral antagonism.

You have clearly not understood the differences in plant and animal immune responses. I think I'd be careful accusing people of not having a basic understanding of the topic.

David

[Hannah Bell]

172. nope, i never mentioned microbial anything, or discussed any

"immune response" in plants v. animals. the first was another poster. the second - i don't think anyone did that. another poster posted a paper on plant viruses, but it w asn't about immune response.

[Fire_Medic_Dave]

174. My fault sorry wrong poster.

[cosmik debris]

131. This crusade has progressed from argument to diatribe to parody.

Persistence is no longer an admirable quality if all you are presenting is parody.

Whether right or wrong, a person does not help their case by going to extremes.

And you passed the extreme point a long time ago.

[mhatrw]

134. Why is it that personal attacks are the favored form of "reasoned debate" on this forum?

Don't you have anything substantive to say? If not, why not just resist the urge to post?

[cosmik debris]

146. I could ask you the same thing.

Why do you keep making personal attacks on the people with whom you disagree?

Why do you persist in posting, reposting, and cross posting the same old stuff?

Once is never enough for the obsessive compulsive.

If you want to "swift boat" Merck, that's OK with me, but you are trying to monopolize this forum for you own personal crusade. And that's just mean to those of us who have heard your parody several times.

Have you considered how closely your behavior mirrors the behavior of a spoiled child?

Is that the image you wish to display?

[mhatrw]

149. I will gladly accept your surrender, but the terms must be unconditional. n/t

[cosmik debris]

154. .

[mhatrw]

161. Indeed it is. n/t

[beam me up scottie]

136. Insert assorted stats from multiple sources and personal paranoid conspiracy theory here.

You work for the Medical Mafia, don't you?

[Hannah Bell]

138. she/he could't have gone to "extremes" if s/he hadn't met an

extreme response, including name-calling such as yours.

two to tango, buddy.

[cosmik debris]

143. Blaming others for your own faults is alway the last resort of a loser. n/t

[WillYourVoteBCounted]

171. I bet TX Gov Rick Perry says his legislators are "poor losers"

for not wanting his "mandate".

[Fire_Medic_Dave]

176. Nah he probably just thinks they are idiots.