What to advise MSers about the HPV vaccine?
You may be aware that for almost a decade young girls living in the UK have been offered the HPV vaccine at ~12-14 years of age. The HPV vaccine is to prevent infection with the sexually transmitted human papillomavirus (HPV) that is known to cause cervical cancer and several other cancers. The current issue is that innovation never stands still, technology moves on and society changes its behaviour. All of these are coming together to create a perfect storm that has major implications for MSers.
The innovation: The current NHS funded vaccine (Gardasil) covers only 4 strains of HPV and reduces the risk of cervical cancer by ~67%. The newer more advanced HPV vaccine covers 9 HPV strains and reduces the risk of cervical cancer by over 90%. The problem is the Department of Health are not yet prepared to pay for the more expensive vaccine that covers 9 strains. It is important to realise that the newer vaccine also covers more strains of HPV that cause warts, in particular, genital warts. Is this important? Yes, it is. If you decide to go onto an immunosuppressive therapy, in particular, an immune reconstitution therapy or IRT, then suppression of your immune system allows the virus to escape and to start replicating. I am aware of two cases at other centres who have had alemtuzumab only to see their genital warts become a major problem. I am also aware of a patient who developed a problem when her common old garden variety of cutaneous warts spread post-alemtuzumab. These anecdotal cases are very important and I now view warts, be they genital or cutaneous, as a relative contraindication to IRTs, particularly the non-selective IRTs such as alemtuzumab and HSCT.
Social changes: There are public health issues that are as relevant to MSers as the general population. HPV is not only a problem for women. HPV is a well-established cause of penile and anal cancer and causes a small proportion of throat and oesophageal cancers. Therefore it makes sense for males to be vaccinated against HPV as well. In the UK boys who have sex with boys and are prepared to admit it can have the HPV vaccine. But what about men? The rationale for targeting the general population is to reduce the pool of susceptible people and thereby reduce the spread of the virus. Epidemiologists call the latter herd immunity. For herd immunity to be effective you typically need over 90% of the population to vaccinated.
The epidemiology of HPV infection is also changing. People are becoming infected later in life and are spreading the virus. Social media and dating apps have revolutionised the dating world and many older people are becoming promiscuous in older age and are having unsafe sex. As a result of this, there has been a large increase in the incidence of sexually transmitted diseases in older people, including HPV infections. This has prompted some commentators to suggest that public health officials extend the HPV vaccine to all women and possibly all men. Why wouldn’t you want to reduce your risk of getting cervical cancer? Isn’t prevention better than having to treat HPV infection and its downstream effects, i.e. premalignant cervical lesions or cervical cancer?
As a result of these trends, an increasing number of MSers are asking about the HPV vaccine. Similarly, when I go to meetings neurologists are asking me for advice or what to do about vaccines, in particular, the HPV vaccine There are several questions that HPV vaccination raises that are directly relevant to MSers.
Question 1: If I have been vaccinated with the older quadrivalent vaccine could I receive the new vaccine to cover the other strains of the virus?
Yes, there is data that shows that the previous vaccination against HPV doesn’t stop your immune system from responding to the components cover the new strains.
Question 2: As I am on a DMT can I have the HPV vaccine?
This all depends on the DMT you are on. For the non-immunosuppressive immunomodulators such as interferon-beta and glatiramer acetate vaccination is not a problem. These agents do not blunt immune responses to vaccines. For the other DMTs to story is not that clear. Fingolimod and ocrelizumab are known to blunt vaccine responses. Vaccine responses to component vaccines on dimethyl fumarate have been studied and were normal. However, I am not aware of any specific studies looking at the HPV vaccine. I would, however, think it would be fine to receive the HPV vaccine if you are on DMF. Teriflunomide is similarly unlikely to blunt the immune response to HPV, but we don’t have specific data on the HPV vaccine and teriflunomide Natalizumab mode of action is unique and is unlikely to affect peripheral immune responses. For the IRTs (alemtuzumab, cladribine, mitoxantrone and HSCT) vaccination should be delayed until after immune system reconstitution.
Question 3: I need to start a DMT, but I want to have the HPV vaccine or extend my cover with the new polyvalent vaccine, how long will I need to wait before I can start treatment?
The polyvalent vaccine at the moment requires 2 or 3 doses with the last dose given at 5 or 6 months. Ideally, to give your immune system a chance to respond to the vaccine you will need to wait until 4 weeks after the final booster, i.e. 6 or 7 months.
Question 4: Should I delay starting DMTs to have the vaccine?
There is no simple answer to this question. You have to balance the risks and benefits of having the vaccine against the risks of untreated MS. In relation to the IRTs, I would suggest going ahead and starting the IRT and delaying the vaccine until you have reconstituted your immune system. Delaying starting an IRT to have the vaccine does not make immunological sense in that the memory responses you have just made to the vaccine could potentially get depleted and depending on the intensity of the immunodepletion may not recover. For maintenance DMTs, in particular, fingolimod, dimethyl fumarate and ocrelizumab, you should probably delay starting treatment to have the vaccine.
Question 5: If I want the new polyvalent vaccine will the NHS cover it?
At present, the answer is no. Public Health England cover the quadrivalent vaccine under the national vaccine programme. If you want to be vaccinated against HPV you will have to cover the costs of the vaccine yourself. This is not too dissimilar to what happens with travel vaccines.
You may be aware that for almost a decade young girls living in the UK have been offered the HPV vaccine at ~12-14 years of age. The HPV vaccine is to prevent infection with the sexually transmitted human papillomavirus (HPV) that is known to cause cervical cancer and several other cancers. The current issue is that innovation never stands still, technology moves on and society changes its behaviour. All of these are coming together to create a perfect storm that has major implications for MSers.
The innovation: The current NHS funded vaccine (Gardasil) covers only 4 strains of HPV and reduces the risk of cervical cancer by ~67%. The newer more advanced HPV vaccine covers 9 HPV strains and reduces the risk of cervical cancer by over 90%. The problem is the Department of Health are not yet prepared to pay for the more expensive vaccine that covers 9 strains. It is important to realise that the newer vaccine also covers more strains of HPV that cause warts, in particular, genital warts. Is this important? Yes, it is. If you decide to go onto an immunosuppressive therapy, in particular, an immune reconstitution therapy or IRT, then suppression of your immune system allows the virus to escape and to start replicating. I am aware of two cases at other centres who have had alemtuzumab only to see their genital warts become a major problem. I am also aware of a patient who developed a problem when her common old garden variety of cutaneous warts spread post-alemtuzumab. These anecdotal cases are very important and I now view warts, be they genital or cutaneous, as a relative contraindication to IRTs, particularly the non-selective IRTs such as alemtuzumab and HSCT.
Social changes: There are public health issues that are as relevant to MSers as the general population. HPV is not only a problem for women. HPV is a well-established cause of penile and anal cancer and causes a small proportion of throat and oesophageal cancers. Therefore it makes sense for males to be vaccinated against HPV as well. In the UK boys who have sex with boys and are prepared to admit it can have the HPV vaccine. But what about men? The rationale for targeting the general population is to reduce the pool of susceptible people and thereby reduce the spread of the virus. Epidemiologists call the latter herd immunity. For herd immunity to be effective you typically need over 90% of the population to vaccinated.
The epidemiology of HPV infection is also changing. People are becoming infected later in life and are spreading the virus. Social media and dating apps have revolutionised the dating world and many older people are becoming promiscuous in older age and are having unsafe sex. As a result of this, there has been a large increase in the incidence of sexually transmitted diseases in older people, including HPV infections. This has prompted some commentators to suggest that public health officials extend the HPV vaccine to all women and possibly all men. Why wouldn’t you want to reduce your risk of getting cervical cancer? Isn’t prevention better than having to treat HPV infection and its downstream effects, i.e. premalignant cervical lesions or cervical cancer?
As a result of these trends, an increasing number of MSers are asking about the HPV vaccine. Similarly, when I go to meetings neurologists are asking me for advice or what to do about vaccines, in particular, the HPV vaccine There are several questions that HPV vaccination raises that are directly relevant to MSers.
Question 1: If I have been vaccinated with the older quadrivalent vaccine could I receive the new vaccine to cover the other strains of the virus?
Yes, there is data that shows that the previous vaccination against HPV doesn’t stop your immune system from responding to the components cover the new strains.
Question 2: As I am on a DMT can I have the HPV vaccine?
This all depends on the DMT you are on. For the non-immunosuppressive immunomodulators such as interferon-beta and glatiramer acetate vaccination is not a problem. These agents do not blunt immune responses to vaccines. For the other DMTs to story is not that clear. Fingolimod and ocrelizumab are known to blunt vaccine responses. Vaccine responses to component vaccines on dimethyl fumarate have been studied and were normal. However, I am not aware of any specific studies looking at the HPV vaccine. I would, however, think it would be fine to receive the HPV vaccine if you are on DMF. Teriflunomide is similarly unlikely to blunt the immune response to HPV, but we don’t have specific data on the HPV vaccine and teriflunomide Natalizumab mode of action is unique and is unlikely to affect peripheral immune responses. For the IRTs (alemtuzumab, cladribine, mitoxantrone and HSCT) vaccination should be delayed until after immune system reconstitution.
Question 3: I need to start a DMT, but I want to have the HPV vaccine or extend my cover with the new polyvalent vaccine, how long will I need to wait before I can start treatment?
The polyvalent vaccine at the moment requires 2 or 3 doses with the last dose given at 5 or 6 months. Ideally, to give your immune system a chance to respond to the vaccine you will need to wait until 4 weeks after the final booster, i.e. 6 or 7 months.
Question 4: Should I delay starting DMTs to have the vaccine?
There is no simple answer to this question. You have to balance the risks and benefits of having the vaccine against the risks of untreated MS. In relation to the IRTs, I would suggest going ahead and starting the IRT and delaying the vaccine until you have reconstituted your immune system. Delaying starting an IRT to have the vaccine does not make immunological sense in that the memory responses you have just made to the vaccine could potentially get depleted and depending on the intensity of the immunodepletion may not recover. For maintenance DMTs, in particular, fingolimod, dimethyl fumarate and ocrelizumab, you should probably delay starting treatment to have the vaccine.
Question 5: If I want the new polyvalent vaccine will the NHS cover it?
At present, the answer is no. Public Health England cover the quadrivalent vaccine under the national vaccine programme. If you want to be vaccinated against HPV you will have to cover the costs of the vaccine yourself. This is not too dissimilar to what happens with travel vaccines.
As you can see HPV vaccination is one of those factors that have to be put in the mix when deciding which is the correct DMT for you. It is not a major factor but is an important factor nevertheless. At the moment I don’t routinely advise my patients on this topic, but it is something that has future health implications, be they sexual, so maybe we need to do this routinely. What is your view on this? Do you think healthcare professionals should be obliged to discuss issue around vaccination before the start of a DMT?
CoI: multiple
Excellent! Never discussed with my neurologist either. At 54 im out of the recommended age group.
It's been my understanding that these vaccines have to be administered PRIOR to exposure to the virus. This is why it's given to youngsters. Am I right? So, I'm 50+ I have MS,I've very likely long ago aquired the whole array of HPVs EBV etc.I'm not sure what's to discuss with my neurologist. Forgive me if it was made clear above? I have this damned degenerative disease that's diminished my discernment.. ��
Mark you are correct; you may be outside the target group of the HPV vaccine. Please see comments below.
Prof G's Twitter feed really complements the blog. Thanks for sharing
Thank you. Twitter may be superficial, but allows me to think aloud. I will continue to do blog posts, but less frequently and hopefully of better quality.
I know they recommend these vaccines at a younger age. I am 34 years old, is that too late? I would like to pay for the Gardasil-9 if that is an option still for me but a GP told me that it's not effective after age 24. But doesn't that depend on how sexually active you are and what you've been exposed to? or is it an age related immune response? I am on Tecfidera.
Gardasil-9 is effective and possibly at all ages. And it doesn;t matter if you have had the other HPV vaccines because it extends the immunity to cover the other strains.
"Gardasil-9 is effective and possibly at all ages."Most likely it is but unless the vaccine has been tested atspecific ages…No-one is going to inject you with you with an untested vaccine. Gardasil-9 is currently licensed for age 9-26 for men and women.but Merck wants to expand the ages."This means Merck, the manufacturer of Gardasil 9, is seeking FDA approval for an expanded age indication for use in women and men ages 27 to 45 for the prevention of certain cancers and diseases caused by the nine human papillomaviruses (HPV) types covered by the vaccine."https://www.precisionvaccinations.com/gardasil-9-protects-both-women-and-men-certain-hpv-cancershttps://www.webmd.com/vaccines/adult-hpv-vaccine-guidelines#
Please note that outside a public health HPV vaccination programme having the newer polyvalent vaccine may be considered a luxury; i.e. if you can afford it you can have it. Deciding to have the new HPV vaccine may depend on your risk of acquiring new HPV infections. As new HPV infections are sexually transmitted you need to consider your sexual behaviour and whether or not you need the cover.
Prof G could MS be a sexually transmitted disease? Your colleague Professor Hawkes seems to think so ;-)J Neurol Neurosurg Psychiatry. 2002 Oct;73(4):439-43.Is multiple sclerosis a sexually transmitted infection?Hawkes CH1.It is proposed that multiple sclerosis may be transmitted chiefly by sexual contact. Arguments favouring this include: migration studies that suggest a transmissible agent in adolescence; clusters of multiple sclerosis which have occurred in low prevalence areas following entry of young males; the similarity of multiple sclerosis to tropical spastic paraplegia, a known sexually transmitted infection with resemblance to primary progressive multiple sclerosis; an increased rate in drug misusers; a similar age of onset and sex pattern to that found in sexually transmitted disease; increased incidence of multiple sclerosis in those using oral contraceptives; low multiple sclerosis rates in societies with a strict moral code; longitudinal shifts in sex prevalence that show an increase in women after the sexual revolution of the 1960s; and important exceptions to the worldwide distribution corresponding to countries with permissive attitudes to sex. Family, conjugal pair, twin, and adoption studies are compatible with an infectious cause of multiple sclerosis if this is sexually transmitted. It is not proposed that sexual transmission is the only cause but that inherited factors create a susceptibility to a sexually transmitted neurotropic agent. It is hoped this hypothesis might encourage a new direction of neurological research.
Yikes..looks like 2002 was Dark Ages of MS research.Then in 2003..https://www.ncbi.nlm.nih.gov/pubmed/14596882"When CD4(+) T cells that recognize antigens within the target organ are activated in lymphoid organs by cross-reactivity with infectious agents, they migrate to the target organ but fail to undergo activation-induced apoptosis because they receive a co-stimulatory survival signal from the infected B cells."
MS and sexually transmitted disease. I remember it coming out at about the time of ECTRIMS. It caused a lot of upset, Prof Miller from Queen Square spent most of the ECTRIMS meeting fire-fighting with the press. It and got Prof Hawkes side-lined.
EBV is spread vertically, typically from mother or grandmother to child, or horizontally, typically from kissing and less commonly sexually. Dorothy Crawford, a world-renowned EBV expert, estimates that about 15% of horizontal transmission of EBV is sexual. If MS is proven to be the cause of MS then it could be argued that MS is potentially a sexually transmitted disease. P.S. I saying this with my tongue in my cheek and playing devil's advocate. At present the epidemiology does not support MS as being sexually transmitted, although Prof. Hawkes' would argue the contrary.
Challenges of independent assessment of potential harms of HPV vaccinesAfter three years of trying to access trial data for HPV vaccines, Lars Jørgensen and colleagues find current transparency policies unfit for their purposeOnly half of potentially eligible reports for a systematic review of HPV vaccines had been obtained after three years, and these were incomplete and contained redactionsRegulators did not have the full data and the manufacturers place restrictions on the dissemination of datahttps://www.bmj.com/content/362/bmj.k3694.full