HPV vaccination reduces cervical cancer by up to 90%

Barts-MS rose-tinted-odometer: ★★★★★
(Cancer Pink Thursday #ffbfc3)

News, news, news! 

In fact, great news (see Lancet paper below)! HPV vaccine cuts cervical cancer rates by close to 90%, using the new polyvalent HPV vaccine (Gardasil-9), which clovers 9 HPV strains. This stunning bit of innovation doesn’t address the other benefits of preventing HPV infection, which include preventing penile, anal, nasopharyngeal and oesophageal cancers not to mention the simple wart. 

So what to advise pwMS about the HPV vaccine?

The HPV vaccine prevents infection with the sexually transmitted human papillomavirus (HPV) which is known to cause cervical cancer and several other cancers.

Cervical cancer: image Medscape.

If you decide to go onto an immunosuppressive therapy, in particular, potent immunosuppressive therapies. The suppression of your immune system allows viruses to escape and to start replicating. This is a particular problem with alemtuzumab and potentially HSCT. So there is a strong augment to get yourself vaccinated, or to upgrade your immunity from the quadrivalent to the polyvalent vaccine, before starting a potent IRT and other immunosuppressive therapy.  

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.

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 and are having unsafe sex later in life. 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?

Cutaneous warts

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 that 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, glatiramer acetate and teriflunomide vaccination is unlikely to be a problem. Similarly for the fumarates, natalizumab, cladribine and alemtuzumab the level of immunosuppression and the window of vaccination are unlikely to affect vaccine responses. However, based on the COVID-19 vaccine studies if you are on an S1P modulator (fingolimod, siponimod, ozanimod or ponesimod) or an anti-CD20 (ocrelizumab, ofatumumab, rituximab) the response to the HPV vaccine is likely to be blunted. 

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, the S1P modulators and anti-CD20 therapies 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. The UK is in the process of switching from the quadrivalent (Gardasil-4) to the polyvalent vaccine (Gardasil-9) under the national vaccine programme. At present, 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.

I predict that HPV vaccination is going to be 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. I have only just started to routinely discuss this topic with my patients. It clearly has future health implications. 

What is your view on this? Do you think MS healthcare professionals should be obliged to discuss issues around HPV vaccination before pwMS start a DMT?

Falcaro et al. The effects of the national HPV vaccination programme in England, UK, on cervical cancer and grade 3 cervical intraepithelial neoplasia incidence: a register-based observational study. The Lancet 2021:November 03.

Background: Human papillomavirus (HPV) immunisation with a bivalent vaccine (Cervarix) was introduced in England, UK, in Sept 1, 2008: routine vaccination was offered to girls aged 12–13 years with a catch-up programme for females aged 14–18 years in 2008–10. We quantified the early effect of this immunisation programme on cervical cancer and cervical carcinoma in situ, namely grade 3 cervical intraepithelial neoplasia (CIN3), registrations.

Methods: In this observational study, we used an extension of the age-period-cohort Poisson model to estimate the relative risk of cervical cancer in three vaccinated cohorts compared with earlier cohorts that were not eligible for HPV vaccination. Data from a population-based cancer registry were extracted on Jan 26, 2021, and were assessed for diagnoses of cervical cancer and CIN3 from Jan 1, 2006 to June 30, 2019 in women aged 20–64 years and who were a resident in England. We used three vaccinated cohorts to account for differences in the school year in which the vaccine was offered and its national coverage. Adjustment for confounding was made using information on changes in cervical screening policy and historical events that affected cervical cancer incidence. Results were compared across models with different adjustments for confounders.

Findings: We used data from a total of 13·7 million-years of follow-up of women aged 20 years to younger than 30 years. The estimated relative reduction in cervical cancer rates by age at vaccine offer were 34% (95% CI 25–41) for age 16–18 years (school year 12–13), 62% (52–71) for age 14–16 years (school year 10–11), and 87% (72–94) for age 12–13 years (school year 8), compared with the reference unvaccinated cohort. The corresponding risk reductions for CIN3 were 39% (95% CI 36–41) for those offered at age 16–18 years, 75% (72–77) for age 14–16 years, and 97% (96–98) for age 12–13 years. These results remained similar across models. We estimated that by June 30, 2019 there had been 448 (339–556) fewer than expected cervical cancers and 17 235 (15 919–18 552) fewer than expected cases of CIN3 in vaccinated cohorts in England.

Interpretation: We observed a substantial reduction in cervical cancer and incidence of CIN3 in young women after the introduction of the HPV immunisation programme in England, especially in individuals who were offered the vaccine at age 12–13 years. The HPV immunisation programme has successfully almost eliminated cervical cancer in women born since Sept 1, 1995.

Conflicts of Interest

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General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice. 

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