Audio File:

Slides: HPV Presentation Slides from Vilnius Conference


HPV: it takes 2 to tango, once, twice or 3 times?
It seems yesterday but it has been more than 10 years since the launching of the first HPV vaccine in Belgium took place.

Those days we did not realize we took a flight for a fascinating journey.

Our knowledge had to be constantly updated.

Universal vaccination is now a priority.

We have to ensure an equal access to a primary mean of prevention.

HPV experts and we as well often had to go back to the chalkboard

Today new strategies will be highlighted,

How can we ban HPV disease?

The subdivision into low and high risk types was the key to develop the new vaccine.

After a decade of HPV vaccination policy Europe still faces a serious health concern!!

Reducing health inequalities between man and woman and within member countries is a EU health strategy core value

Many providers spend a lot of time discussing with hesitant parents, effective recommendation tools and engagement are needed to increase worldwide coverage.

How good did we perform?

It’s all about Prevention
1.a Secondary prevention.

The combination of HPV-sensitive and cytology-specific triage leads to optimal screening.

Organised, cost-effective prevention is to the best approach.

Molecular markers may be helpful, when the viral expression can be measured it may indicate advanced stages of infection

But it is only a disappointing step when treatment needs to follow

1.b Primary Prevention = (vaccination)

Focus must be placed on promotional campaigns,

disbelief and distrust lead to low uptake.

A vaccination platform should be created, school vaccination programs remain a good option.

Vaccination stimulates the immune system.

IM vaccines are based on virus-like particles (VLPs).

In my country The HPV vaccination is available since 2006 and since 2007 covered by the national health system.

The vaccination rate in Flanders for HPV (2016) shows that 91.2% of the target population was correctly vaccinated at the correct interval and depending the age group with a 2/3 dose schedule.

Yet information policy is decisive.

Very effective prophylactic vaccines are available in my country:

  • Cervarix® the Bivalent 16/18 Cervarix: 68.86 € refund (+)
  • Gardasil® the Quadrivalent 6/11/16/18: 118.18 € refund (+)
  • Gardasil9® Nonvalent: 138.5 € Refund (+ since june )

A different HPV profile has been observed in adolescents, their genotypes differ from adult women. Now that a newer Nonavalent vaccine exists, using it for boys and girls, in a school tender, would be the best goal!!

How about Worldwide prevention … What does it look like ? Cancer kills worldwide more people than AIDS, TBC and Malaria.

Cervical cancer is the 4th most common cancer with 528000 new cases worldwide in 2015.

In third world countries, cervical carcinoma is the 2nd most common, often diagnosis is late and cure is impossible.

Worldwide more than 250 M vaccination doses have been administered in 10 years time (most of them in wealthy income classes)

This means that 500,000 cancers will not occur in the next 80 years

In our Western countries, a universal vaccination program for adolescents is widely accepted.

FIGIJ develops currently, under the name ImaGYNations, a global policy strategy to launch a 1 dose vaccine policy through education programs, in the 3rd world.

WHO support and funding is requested.

In the third world countries there is no uniform policy, although they have the highest cervical cancer incidence (84%).

75 countries are involved in the vaccination campaign

(The national introduction of a national vaccination program and start year are represented )

  • 2006: Puerto Rico, United States
  • 2007: Australia, Belgium, Canada (2007-2009), France, Germany, Italy (2007-2008)
  • 2008: Bermuda, Fiji, Greece, Greenland, Luxembourg, Marshall Islands, Mexico, New Zealand, Panama, Spain, Switzerland, UAE (Abu Dhabi), United Kingdom
  • 2009: Denmark, Federated States of Micronesia, Norway, Palau, Portugal, San Marino, Slovenia
  • 2010: Bhutan, Ireland, Latvia, Malaysia, Netherlands, Republic of Macedonia, Romania, Singapore
  • 2011: Argentina, Cayman Islands, Guyana, Iceland, Israel (Females), Japan, Kiribati, Peru, Rwanda (Gavi)
  • 2012: Brunei (2012-2015), Bulgaria, Colombia, Czech Republic, Lesotho, Sweden, Uganda (Gavi)
  • 2013: Finland, Libya, Paraguay, Suriname, Trinidad and Tobago, Uruguay
  • 2014: Austria, Barbados, Brazil, Ecuador, Hungary, Republic of Seychelles, South Africa
  • 2015: Botswana, Chile, Israel (Male), Philippines, Uzbkistan (Gavi) (Malawi, Mozambique and the Comoros are the countries with highest-frequency, N America and Oceania score lowest

The countries with HPV in the national immunization program, the highest population density is clearly less vaccinated.

The safety profile of HPV vaccination remains a controversial point.

The impact of gossip on alleged multiple sclerosis and autism led in Japan to an almost complete collapse of country coverage.

The same thing happened in Denmark, where the coverage suddenly fell.

Also in India, social anti-vaccine campaign is gaining field, even for measles and rubella

A recent paper by Grimaldi (2017) showed no statistically relevant association of these diseases with vaccination. Continued vigilance will of course be dealt with.

Vaccination programs are quickly undermined by disinformation and rumors. Correct information of the mother, the father, the girls and the boys is particularly important to ensure proper coverage (WHO 2013)

Control studies on the safety of available vaccines have indicated that local reactions and mild febrility may occur.

The redness for example is dependent on the amount of VLPs and adjuvant, the side effect is mild or moderate.

24 Million doses of the Gardasil 9 have yet been given. Pharmacovigilance confirms that the HPV vaccine is safe (Donovan et al 2011) (they studied multiple sclerosis, connective tissue disorders , Guillain Barré syndrome, Type1 diabetes, autoimmune thyroiditis and idiopathic thrombocytopenic purpura. A multivariant analysis corrected the risk model for family history, medication and co-vaccination. The study took place in France )

Can we do better?

  • sooner ?
  • broader ?
  • less ?

Sooner ?

There is evidence that mother / father / child transmission occurs. To vaccinate before the age of 9 years is not yet recommended. Belgium starts only at 12y … But Optimal timing is desirable!


Gender neutral vaccination can rule out the virus. “There is no herd if the herd is left behind”

With a coverage of less than 50%, the vaccination of boys is mandatory(15 countries including Australia UK and USA have already included the boys in the vaccine programs)

Can we go less?

Are we going use 1, 2 or 3 doses? The standard says 2 before 15 and then 3, Maybe 1 is enough between 9 and 13, In case of high risk profile the indication remains 3 doses.

How can we do better?

  • Go sooner? Go broader? Go less?
  • Before 12?
  • Boys and girls?
  • How many types?
  • 1,2,3 doses?
  • Vaccinate before 12?

The question is whether a viral infection at a very young age has an impact on the long term?

Whether this is of any significance remains an open question.

A meta-analysis of published data provided more insight.

A total of 20 studies or 3128 mother-child pairs were included in the analysis.

Limited to only high-risk HPV positive mothers, the transfer risk was found to be 45%.

Father transmission is also a reality, the oral transmission of one or more types is described in detail (Lacour and Trimble, 2012).

Gender neutral vaccination can rule out this virus.

Margareth Stanley claims that if only a small vaccination ratio for boys is achieved, this will always have a beneficial effect on virus circulation. (With this strategy, in 2050, the HPV 16 infection would fall by 88-94% in women and 68-82% in men. The inclusion of men is useful (Garland 2010))

Multiple genotypes should be taken in account when vaccinating

Multityping so far so good, but how many types?

Meanwhile we know that the spectrum of HPV-related anomalies in young people differs from adults.

What are we looking at? (A retrospective study on the “High Frequency of Genital Human Papillomavirus Infections and Related Cervical Dysplasia in Adolescent Girls in Belgium” (Ref 2014 EJCP M. Merckx et al) studied young adolescent women and not only an unexpectedly high rate of HPV infections was found In minor girls (15 to 19 years), it also appeared that the genotype of the HPV types is different from that of the adult (19 to 25 year) population)

An observational study included 4180 samples of opportunistic screening data and examined the cytology and HPV presence by PCR

The average age was around 17 years. The HPV frequency for the 14 onco types tested was 15.7%, Multityping increased with age (39%).

The top 5 of high risk genotypes observed in the young population were found less frequently in the older adult group

There is concern about a potential shift of hr HPV types, which might fill an ecological niche.

Why these differences occur is unclear, hormonal factors may have an impact.

The vaccination with HPV vaccines is expected to reduce the prevalence of HPV vaccine types, but problems may arise as to how this may affect the distribution of other oncogenes. Escape mutants are unlikely because HPV viruses are genetically very stable.

Even if the shift in types occurs, the risk of cancer with HPV 16 and 18 is still much higher than the risk of cancer by other types (Dochez et al., 2014).

There are also other emerging types of human papillomavirus

G. Bogani presented new data for the 31st HPV 2017 conference.

The onset of HPV types is changing possibly by introducing a quadrivant and bivalent vaccination as well as because of migratory flows.

The study of the National Italian Cancer Registration Center on the prevalence of HPV types gave accompanying results.

13,665 patients were retrospectively vaginal and cervical Screened between 1998-2015 to identify changes in HPV types:

HPV16 and 18 are the two most common HPV types, ie in 2664 (19.4%) patients.

Other HPV species from 9vHPVv are commonly observed in women. (HPV 31, 33, 45, 52 and 58 were 943 Patients respectively (6.9%), 328 (2.4%), 208 (1.5%), 426 (3.1%) and 601 (4.4% )).

Among the HPV types not included in 9vHPV they noticed HPV53 (6.9%) followed by HPV51 (n = 536, 3.9%) and HPV66 (n = 521, 3.8%).

Other HPV types had limited prevalence (lower than 2.5%).


Further investigation is needed to evaluate any cross-protection of 9vHPV against HPV53, 51 and 66.

Globally, 82% of genital high grade lesions in Europe are related to the 9 types of gardasil

89% of HPV related genital cancers are caused by the types of Gardasil 9,

Decisions on HPV vaccination in healthcare should be based on proven high efficiency against HPV types included in the vaccine in order to ensure wide long term protection.
Cross-immunity is apparently short-lived and disappears after 4 to 6 years … choices must be determined by the indications the vaccine was meant for

Shall we stick to one, two or 3 doses ?

There is still controversy about starting with less doses

Goodbye to the three-dose schedule under 15 y has been based on the comparison of the antibody response

Anyone who starts after 15y must continue with the three dose schedule, this applies also to those who have an attenuated immune system

The biggest changes involved are two doses of HPV vaccination, starting at the age of 9 years, as well as the recommendation to start an HPV vaccine schedule if a child is victim of sexual abuse.

We should know that vaccination at 9 gives a better immuno-response and apparently 12 months between 2 vaccinations is better than 6

Vaccine exchangeability?

Both can be used if for example the vaccine is unknown or unavailable, then one of the two HPV vaccines can be used to complete the recommended schedule.

Now the one dose is being discussed and SAGE’s position, the Scientific Advisory Group of Experts (WHO) will be decisive

And then, even thinking beyond …

What after 30 years? the guidelines for vaccination should also be adapted to older women.

It is clear that HPV vaccines are most effective in pre-exposure administration because they do not work therapeutically. Up to the age of 30 y vaccination is still cost-effective, after this period, cost-effectiveness decreases

For sex workers, on the other hand, (from 17j to …) the risk may persist and we know that some start with sexual activity at a later age. This justifies additional research into the potential benefits and the feasibility of catch-up vaccinations among prostitutes.

And then there’s the sexual abuse of minors

Because abused children are at increased risk for unsafe sexual practices, they are at higher risk of HPV acquisition. Because of their abuse a high risk behavior occurs (sex for money, drugs, shelter), they become more likely to be victims of repeated abuse and sexual activity at an early age.

This scenario causes an unfavorable sexual script for a child

My engagement in forensic medicine triggers me to discuss HPV

Medical prophylactic STI care is a guideline

but HPV prevention is lacking ….

Although the exact prevalence is unknown, it is estimated that 12-40% of children experience a certain form of sexual abuse in childhood.

Shame and stigma prevent its victims from seeking help.

About 1/5 women experienced incest and the average age of abuse is estimated at 12 years.

Victims come from all cultural, racial and economic groups.

(In Belgium, in 2016, 15% of cases of child abuse categorised sexual abuse, which is similar to the sexpert data (Buysse et al., 2013). The age of 10 to 13 is a vulnerable period.

On a total of 3032 reports in our country more than half are under 18 (64%)).

The succes of an HPV vaccination policy is depending on the timing id est before or after exposure

An HPV 9 vaccination strategy can be part of immediate medical care.

Child abuse requires protection


Support for prophylactic (and non-therapeutic) vaccination is encouraged by the favorable timeline showing that the safety period is already more than 30 years (Van Damme et al)

In a brave new world, we have to consider vaccinating earlier and of course boys, regardless their sexual orientation.

Last but not least

“What is the lucky number? 9! Of course 9 y and 9 v “

An ounce of protection is worth a pound of cure

There is no need as strong in childhood as protection


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In the meantime, the NCQA has proposed early 2017 to combine HPV vaccination for adolescents with Meningococ, Difteria, Tetanos and Pertussis for both boys and girls

NCQA = “The National Committee for Quality Assurance is a private, 501

(c) (3) not-for-profit organization dedicated to improving healthcare

quality. Since its founding in 1990, NCQA has been a key figure in

driving improvement throughout the healthcare system,

helping to elevate the issue of health care quality to the top of the national agenda)


Until today in our country the HPV vaccination only happens for girls.

Worldwide, the policy is very different.

In the meantime, the NCQA has proposed to combine HPV vaccination for adolescents with Meningokok, Difterie, Tetanos and Pertussis since early 2017 for both boys and girls In Flanders, 2 years after the HPV vaccination they are offered for free, but if the vaccine is administered simultaneously with others, better coverage will go hand in hand.
The main barrier in health policy is still the refusal of parental side. This because of the negative connotation about safety and because the relationship with sexual activity.

(ref Richmond AK, Priyanka S, Mahmood T, MacDougall J, Wood PL, (2016)) Paediatric & Adolescent Gynaecology in Europe: Clinical Services, Standards of Care and Training, Journal of Pediatric and Adolescent Gynecology 29(3):299-303 The Lancet Global Health 2016 4, e453-e463DOI: (10.1016 / S2214-109X (16) 30099-7