Sexual health in the post-HPV vaccination era: implications for genital warts and cervical screening

Quadrivalent HPV vaccination (qHPV) for adolescent girls is recommended and publicly financed in a number of countries.  This intervention promises to prevent up to 70% of HPV generated cancers in those vaccinated, as well as vastly reducing the burden of genital warts (GW).  In relation to prevention of HPV generated cancer and cancerous lesions, its effective contribution will need to be evaluated in relation to cervical screening, and as part of an overall cancer prevention strategy: the question of the right mix of interventions, including vaccination and its relation to the method and interval of screening, are questions of ongoing debate.  Regarding HPV generated GW, however, it may already be possible to score up certain gains.

A recent Swedish national cohort study of 2.2 million women aged 10-44 years offers evidence of the effectiveness of qHPV in relation to genital warts (GW) that complements the findings of clinical trials regarding its therapeutic efficacity (http://jnci.oxfordjournals.org/content/105/7/469.abstract?sid=e0d178cd-8985-42e4-b934-201c858ca42e). The results of efficacity trials follow pre-specified inclusion criteria and are consequently not generalizable.  Now, however, thanks to the rigorous registration of patients and treatment in Sweden, these researchers have been able, so they claim, to gain an insight into the effectiveness of the vaccine – better than would been possible in many other countries.  Results are stratified by age: vaccine effectiveness was 93% against GW where administered at under 14 years;  80% for girls aged 14-16 years; 71% for those aged 17-19; 48% for those aged 20-22 years; and effectively zero for those above 22 years.  This study confirms at the level of national surveillance the general picture offered, at the level of the STI clinic, by Read & Fairley’s account of the “near disappearance” of heterosexually transmitted GW from  vaccinated <21 years, four years after the introduction of a qHPV program in Melbourne, Australia (vaccination restricted for three years to girls ≤26 years and thereafter to 12-13 years) (http://sti.bmj.com/content/87/7/544.abstract?sid=58e7950b-ccdf-4899-b67b-c7ad3b00081d).

Given the steep decline in effectiveness of qHPV for girls aged >13 years as indicated by these studies, it is disquieting to discover in a recent study of US parents expressing their non-intention to have their teens vaccinated with qHPV that as many as 11% of them gave as the reason that their children were “not yet sexually active”.  The study (Darden & Jacobson) was initiated on the basis of data from the National Immunization Survey, and involved asking parents of children who were “not-up-to-date” with qHPV (along with Tdap and MCV4) and who further indicated their non-intention to vaccinate, the reasons for their decision (http://pediatrics.aappublications.org/content/131/4/645.abstract?sid=082b138f-5a8d-47c5-bf41-5c45d343b129).  The percentage of US girls in the immunization cohort taking up the full three doses of qHPV has increased over the three years 2008-2010 from 17.9% to 32%, but remains substantially below that for Tdap and MCV4 (81.2% & 62.7% for 2010 as against 32%); there is a rising percentage giving as reason for non-vaccination “safety concerns/side effects” – rising over the three years from 4.5% to 16.4%.

The long term implications of incorporating qHPV into the STI toolkit are very unclear, though the reduction of GW is, of course, very welcome.  Aside from the much discussed question of how the choice of cervical screening method should complement vaccination in a post qHPV era (http://sti.bmj.com/content/87/Suppl_1/A14.3.abstract?sid=190a5031-ecc8-4f7f-a4bc-1411d34798f1) there is the question of how a woman’s knowledge that she has been vaccinated is likely to impact on her behaviour in relation to cervical screening (http://jms.rsmjournals.com/content/18/1/41.full.pdf+html?sid=9162f5ac-9762-43c5-bcd8-5e09044c2368;

http://ruizscience.webs.com/HPVvaccineCervicalCancerScreening.pdf).  If we suppose a moderate level of HPV cover combined with a partial collapse in cervical screening compliance what will be effect on the incidence of cervical cancer? Given many health systems are already embarked on the route of qHPV vaccination, it is imperative to maximize the vaccination uptake.  The study of Darden and Jacobson may indicate the challenge posed, with the integration of qHPV into the toolkit, by the urgent need to ensure we communicate the right public health messages.