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Prevention of anogenital cancers in women may be an additional benefit of HPV vaccination

14 Oct, 16 | by Leslie Goode, Blogmaster

Cervical cancer is evidently the most important, but by no means the only, health risk that vaccination against HPV aims to avert. The potential impact of vaccination on other cancers (not to mention genital warts) may also be a factor in estimating the cost benefit of achieving higher vaccination coverage, as well as determining priorities for vaccination programmes (e.g. the relative importance of achieving high coverage for males).  Recent studies have investigated the role of HPV in the rising incidence of head and neck – especially oropharyngeal – cancers (Field & Lechner/STIs; King & Sonnenberg/STIs), and in the development of anal cancers amongst MSM (Poynten & Garland/STIs).  The dramatic impact of vaccination programmes on the prevalence of genital warts has already been attested both in Australia, where vaccination was introduced in 2007 (Chow & Fairley/STIs ), and, more recently in the UK (Canvin & Mesher/STIs ).

In addition to these benefits of HPV vaccination, a recent Danish nationwide cohort study (Sand & Kjaer (S&K)) draws attention to another relatively limited, but nevertheless significant, benefit in the shape of a range of anogenital cancers in women – i.e. anal, vaginal and vulvar cancers.  These seem to be strongly associated with the occurrence of high grade cervical intraepithelial neoplasia (CIN2 & 3), and should therefore be numbered amongst the adverse effects of HPV that vaccination may help to prevent.  Given the relative rarity of these cancers (total yearly incidence in UK, both male and female, is currently about a quarter of that of oropharyngeal cancers), an important advantage of S&K’s study is its impressive scale.  It investigates no less than 2.8 million women born 1918-1990 over the period from 1978 to 2012. Also, unlike similar studies, it is able to control not only for age, but for a range of potential confounders such as socio-economic status and smoking.  The use of CIN2/CIN3 as a proxy for HPV infection seems well supported by the evidence (Tachezy & Vonka/STIs; Azwa & Harun (STIs)).

The key findings of the study were as follows.  Relative risk of anal, vulvar and vaginal cancers following CIN2/3 as against no such history was found to be greatly increased: RR 2.8, 2.5, 8.3 after CIN2; 4.1, 3.9, 17.4 after CIN3.  Risk was particularly high in the first year after CIN; but the increased risk persisted, suggesting the effect could not be attributed to surveillance bias.  So, for example, analysis showed increased risks of anal, vulvar and vaginal cancers at ≥25 years after CIN3 diagnosis of RR 4.8, 3.2, and 5.5, respectively.  In non-cervical anogenital cancer, HPV16 was the most frequently detected HPV type.  The fact that cancer risk following CIN3 is substantially greater than it was following CIN2 suggests to the authors that the cause of both may be attributable to an inadequate immune response to HPV in certain women, leading to a failure to clear the infection.  The propensity of persistent HPV to spread to the entire anogenital region explains the range of cancers (anal, vaginal, vulvar) in respect to which these women seem to be at heightened risk (see Simpson & Turner/STIs ).

Fresh WHO guidelines on gonorrhoea management + latest US surveillance data on gonorrhoea resistance

13 Oct, 16 | by Leslie Goode, Blogmaster

The emergence in various locations of resistant strains of Neisseria gonorrhoeae (Ng) is narrowing the therapeutic options. The recent (July 2016) WHO Guidelines, revised from 2003, reflect the concern both to treat effectively and steward our remaining defences against the infection in a globally coordinated manner.  They recommend either dual therapy with either single dose 250g intra-muscular ceftriaxone or 400g oral cefixime combined with 1g oral azithromycin (preferred options), or else single therapy with either ceftriaxone, cefixime or 2g spectinomycin).  The choice between these options will depend on local considerations, including Ng susceptibility data.   In the event of treatment failure following WHO-recommended dual therapy, they recommend any of: 500mg ceftraxone, 800mg cefixime, 240mg gentamicin, or 2g spectinomycin, each of them in combination with 2g azithromycin.

Reported surveillance data for a given location will be crucially important, then, for determining at local level the best options for treatment.  Given the global dimension of the threat, however, this data may also be potential evidence for global trends.  Hence the wider interest of the latest (2014) US surveillance data from the Gonococcal Isolate Surveillance Project (GISP)).  Hitherto, the US picture (as in the UK) has been one of steady progression (2006-2011) in prevalence of Ng isolates exhibiting reduced susceptibility (cefixime: MIC ≥0.25 μg/mL; ceftriaxone: MIC ≥0.125 μg/mL), interrupted by a decline in 2013; this is the pattern both for cefixime (0.1%-1.4%-0.4%) and ceftriaxone (0.1%-0.4%-0.1%) (see also Kirkcaldy & Bolan (STIs)).

So where do the latest (2014) data point? As regards cefixime, to a return to the pre-2013 upward trend, it seems, with prevalence rising once again from 0.4% to 0.8%; with ceftriaxone, to the maintenance of the 2013 prevalence level (0.1%).  Presumably, it is the prevalence levels of ceftriaxone that, in the US, constitute the primary focus of concern – since, as in the UK, that is the drug currently recommended, along with azithromycin, for dual therapy.  (See  Town & Hughes (STI) for  an equivalent report of ceftriaxone resistance in the UK).  But the greatest surprise of the 2016 GISP report is the sudden rise of decreased susceptibility to azithromycin: from 0.6% prevalence of reduced resistance strains (MIC ≥2.0 μg/mL) in 2013 to 2.5% in 2014.  The report comments that the recommended dual therapy with azithromycin is unlikely to be a contributor to this trend – though it is possible, they argue, that the small increase in the azithromycin monotherapy by US STD clinics over the last decade could have had some influence on the prevalence of azithromycin resistant strains.  There is evidence of high or rising levels of azithromycin resistance in other locations (Dillon & Thakur (STIs); Bala & Ramesh (STIs)), including, recently, the UK (Chisholm & Fifer/STIs).

Cochrane says: Chlamydia screening may have very limited impact, but more research is needed

3 Oct, 16 | by Leslie Goode, Blogmaster

There is a strong rationale for systematic Chlamydia screening, and it is widely recommended and practised. Yet there are harms associated with the screening process (Low(STIs)), and, of course, serious concerns about its cost-effectiveness (De Wit & Kretzschmar (STIs)).  This lends urgency to the question of whether Chlamydia screening works – addressed in a recently published systematic review for the Cochrane Database:  ‘Screening for genital chlamydia infection’.

It all depends, the authors claim, on what we want screening to do: whether it’s a general reduction of prevalence in the population that we’re aiming at, or the prevention of serious sequelae such as PID (Pelvic Inflammatory Disease) in individuals.  The strict Cochrane exclusion criteria (especially that of ‘reporting a pre-specified primary outcome’) reduce the pool of evaluated studies to just two addressing the impact of screening on Chlamydia prevalence – only one of which (not, as it happens, an RCT) addresses impact on prevalence in the general population (Schmid & Kretzschmar (STIs)).  Regarding the impact of screening on reduction of PID incidence, the field narrows to just four RCTs (Andersen & Olesen (STIs);  Ostergaard & Olesen; Oakeshott & Hay; Scholes & Stamm).

Respecting the impact on prevalence, Schmid & Kretzschmar (STIs) observe very little effect (RR 0.96), but the quality of evidence is rated, on Cochrane criteria, as ‘low’.  As for PID prevention, an effect was observed (overall RR 0.68), but unfortunately was considerably less pronounced in the two studies with low risk of selection bias (Andersen & Olesen (STIs) and Oakeshott & Hay) (RR 0.80) than with the other two studies ((RR 0.42).  This evidence was consequently downgraded from ‘high’ to ‘moderate’.

So there continues to be no evidence at present for a positive impact of screening on general prevalence, though further research could possibly modify this assessment.  As regards the incidence of PID, some limited degree of positive impact may have been demonstrated – though whether systematic screening interventions will turn out to be cost-effective is another question (De Wit & Kretzschmar (STIs)).  The reviewers point out there is another important trial that is still on-going (hence not eligible for inclusion): Hocking (STIs).  The latter – a study being undertaken in Australian GP practices – involves ‘opportunistic’ testing (as defined by Low (Low(STIs)) rather than screening proper (i.e. ‘systematic’ screening).  However, given that this is the form of intervention being undertaken in many places including the UK, its final results will no doubt be of great interest.  On the basis of the study’s findings to date, the verdict seems unlikely to be favourable (Yeung & Temple-Smith (STIs)).

First study of population-level preventative impact of Medical Male Circumcision and ART on HIV incidence in a country of sub-Saharan Africa

14 Sep, 16 | by Leslie Goode, Blogmaster

Clinical studies have demonstrated the potential effectiveness of ART (HPTN 052) and Voluntary Medical Male Circumcision (VMMC) (Gray & Kigozi/STIs) as preventative measures against HIV.  This led WHO/UNAIDS to launch a Joint Strategic Action Framework (JSAF) setting a target in 14 priority sub-Saharan countries of 80% VMMC by 2016.

What, then, are the potential gains of ART and VMMC interventions in these countries?  Comparative ecological studies have shown the population-level impact of male circumcision as a cultural practice (MacLaren & Vallely/STIs). Various mathematical modelling studies have sought to quantify that potential effect of interventions both in the realm of VMMC (Jenness & Cassels/STIs) and ART (Shafer & White/STIs)  (though other studies have highlighted the challenges that scale-up of these interventions is likely to present (Kaufman & Ross/STIs)).

Now, for the first time, a study has sought to quantify the real-life population-level impact of these interventions.  Kong & Gray (K&G) base their study on data from the 1999-2013 Rakai Community Cohort Study (Uganda)).  Among the 45 Rakai communities (44,688 participants surveyed over 24.6 years), VMMC coverage had, by 2013, increased from 19% to 39%, and ART had risen, in males, from 0% to 21%, and, in females, from 0% to 26% – and HIV incidence had fallen, concurrently, from 1.25 per 100 person-years to 0.84 per 100 person-years in males, and from 1.25 to 0.99 in females.  As regards VMMR, each 10% increase in the rate was associated amongst males with a decline in incidence that could be quantified, on multivariate analysis, at 0.87 – though, in females, the reduction was statistically insignificant.  As for ART, the decline attributable was not statistically significant in either case, but, when ART coverage was modelled as a categorical variable, and coverage of over 20% was compared with coverage of under 20%, a decline in HIV incidence was observed in the former group of the order of 0.86 among males, and 0.77 among females.

These results are not surprising.  VMMC is, in the first instance, protective of men – though, of course, in the longer term women too will benefit from any population-level effect. (There is, in fact, a worrying possibility, investigated by Maughan-Brown & Thornton/STIs, that men could incorrectly assume that their VMMC will be directly protective of their partners, and modify their behaviour accordingly.)  As for ART, here too the (as yet) limited impact in Rakai is what we might have expected.  Tanser & Newell, in a South Africa-based study only observed significant association when ART coverage was over 30%.  However, population level decline in incidence – especially that associated with VMMC – is encouraging.  The results of this study allow us to predict that increasing VMMC coverage more than 40% could reduce male incidence by approximately 39% at population level.   A major limitation of the study, of course, is its assumption that sexual networks, and hence HIV transmissions, are internal to the community. However, a recent study by Chemaitelly & Abu-Raddad/STIs would seem to indicate that, in a context like sub-Saharan Africa the contribution of networks going beyond the wider community is likely to be limited.

Viral suppression through ART prevents HIV transmission between long-term sero-different MSM and heterosexual partners regardless of condom use

8 Sep, 16 | by Leslie Goode, Blogmaster

The HPTN 052 study demonstrated the preventative benefit of ART, showing a dramatic 96% reduction in HIV transmission in HIV+ participants randomized to early ART initiation compared with the group that deferred treatment.  This is very encouraging.  But from the perspective of a gay person considering the risk of engaging in condomless sex with a long-term HIV+ partner, these results do not provide an adequate basis on which to make a decision.  For a start, HPTN 052, like other such studies, focuses largely on heterosexual couples engaging in vaginal sex – which is recognized to carry only a fraction (c. 0.1) of the risk of HIV transmission of anal sex.  Besides, the study reports high levels (93%) of condom use.  Much remains obscure, therefore, as to the level of protection that a gay person could reasonably expect from ART against HIV transmission through condomless anal sex with a long-term partner.

This question is squarely addressed, however, in a recently reported prospective observational study – PARTNER (Partners of People on ART – A New Evaluation of the Risks) – involving 888 sero-different MSM (330) and heterosexual (548) couples reporting condomless sex who contributed a total of 1,238 eligible couple-years.  This study did not limit itself to establishing cases of transmission, but conducted phylogenetic analysis in those cases in order to determine whether or not the transmission had resulted from sex with the long-term partner.  Of the 11 transmissions that took place in the course of the 1,238 couple-years (10 amongst heterosexual, one amongst the MSM, couples), none were found to be phylogenetically linked.  The paper also examined the association between the HIV transmission which did take place (i.e. not from primary partner) and the sexual behaviours reported by HIV- partners.  Not surprisingly, this was found to be elevated in heterosexual couples where anal sex was reported, and in MSM where anal sex was receptive and receptive with ejaculation (1.68 and 2.70 per 100 couple-years, respectively).

With the couple-years accrued hitherto, appreciable levels of risk over the long-term, especially with anal sex, cannot yet be excluded: a rate of 2.2 per 100 couple-years remains the upper limit (20% over ten years) – though, of course, the risks could prove to be considerably lower than this.   With a view to arriving at a more precise estimation, the MSM side of the PARTNERS study remains ongoing.  So far, however, the news seems to be good.

Aside from its implications for personal decision-making about condom use, the question of the preventative effectiveness of ART could presumably also have relevance for health policy decisions affecting resource allocation that involve determining the relative priority to be accorded to interventions promoting engagement and retention in treatment as against other interventions (e.g. PrEP) (Punyacharoensin & White/STIs/blogNHS kicks PrEP into the long grass/STIs/blogs). The greater the effectiveness of viral suppression through ART as an HIV prevention tool, the better the case for prioritizing interventions to achieve higher targets for engagement and retention in treatment.

How Mobile Technology Can Lead to Improved Care of STIs – by Julie Potyraj

16 Aug, 16 | by Leslie Goode, Blogmaster

Blog by Julie Potyraj, Community Manager, Milken Institute School of Public Health at The George Washington University


As we move into an era where our phones do everything from lowering the temperature in our homes to arranging a ride, it comes as no surprise that these devices also offer a new way to meet and engage with potential sexual partners. Along with the rise in popularity of dating apps, there has been an increase the incidence of sexually transmitted infections. In 2014 the CDC received the highest number of reports in history for chlamydia, syphilis, and gonorrhea in the United States. The challenge is to figure out a way to use technology to safeguard our sexual health in addition to meeting new partners.

In an effort to encourage online daters to get tested, a study published in Sexual Health posted advertisements for free HIV test kits on the dating website Grindr. In exchange for providing personal information about their health status and behaviors, participants received a free test kit. Not only did this intervention encourage HIV testing, but the study also showed an increase in the number of young men seeking treatment. Even a few of the volunteers who helped with the study became aware of their statuses.

The Grindr study shows that the privacy and comforts of home testing can be a desirable alternative to visiting a doctors’ office. Providing this alternative could potentially increase the number of people seeking testing for STIs. Improved testing technology used in tandem with the convenience and range of a mobile device introduces the opportunity to connect huge numbers of people with diagnostic interventions. The more people who get tested, the more data there is available. If this trend continues, we can anticipate an incredible expansion in electronic reporting, STI surveillance, and the use of this data in health informatics.

Mobile technology contributes to the collection of big data, which is defined as complex data sets that are so large that they cannot be evaluated by traditional data management tools. With better surveillance of STIs, medical providers can reach and identify commonly overlooked demographics by tracking trends to improve diagnostic care, interventions, patient outcomes, and cost of care.

More widely available data about STI outbreaks and incidence rates could help health care providers to make more informed medical decisions. For example, a care provider who identifies chlamydia from a patient’s urine could use big data to inform her decision about what type of antibiotic to prescribe. She may find there is an increasing incidence of azithromycin-resistant chlamydia in her city or state. Her awareness of this emerging trend would lead her to prescribe her patient with doxycycline instead; providing better medical care through informed treatment decisions.

The use of mobile technology can broaden epidemiologic surveillance and trend analysis of STI infections, offering knowledge to care providers that is otherwise unobtainable. More people using STI diagnostic interventions leads to the more people being tested and in turn better access to STI statistics. Mobile technologies, and health interventions that make use of them, can contribute to the collection of timely, relevant data. The analysis and interpretation of this data offers the possibility of improving health care quality and outcomes for patients.

Julie Potyraj

Is increasing gonorrhoea resistance in MSM is a result of more treatment, rather than greater sexual activity?

20 Jul, 16 | by Leslie Goode, Blogmaster

Emerging antibiotic resistance to the last-ditch treatment of Neisseria gonorrhoeae compels health policy-makers to balance opposing concerns.  On the one hand, successfully combating spread of the infection requires targeted treatment of core-group individuals.  On the other, a focus on the core-group causes a rebound in core-group incidence, with maximal dissemination of resistance (Chan & McCabe/STIs (C&M); Chan & Fisman/STIs).

Recent public health orthodoxy has tended to favour the more intensive screening of core-group individuals (Ison & Unemo (STI); Giguere & Alary/STIs; Lewis/STIs).  However Fingerhut & Althaus (F&A), in a recent modelling study, seek to shift the balance in the opposite direction.  They claim their model demonstrates that the wide disparity in the spread of resistance spread as between populations of MSM and of HMW (heterosexual men and women) reflects differing levels of treatment rather than differences in sexual behaviour (‘more sexual partners’).

So far as concerns the first part of the claim (‘gonorrhoea spreads faster with more treatment’), F&A’s findings corroborate those of C&M.  However, in coupling this with the claim that gonorrhoea spread is not the result of sexual behaviour (‘gonorrhoea (does not) spread faster with more sexual partners’) they place the balance of responsibility for spread with the prevailing policy of treatment.  This is presumably intended to push policy makers in the direction of a more conservative attitude to targeting testing and screening.

But can F&A really justify this  change of emphasis by differentiating the respective contributions of ‘more treatment’ as against ‘greater sexual activity’ to the difference in resistance between MSM and MSW popultions ?  We are wrong, the authors argue, to assume that ‘more partners’ amongst the MSM population necessarily entails more transmissions (p. 11) – and their model apparently demonstrates this.   A common sense response, however, would be to object that ‘more partners’ presumably implies ‘more sex acts with more partners’ – and that, even if ‘more partners’ does not in itself entail more transmissions, ‘more sex acts with more partners’ might certainly be expected to do so.

Interestingly, Althaus in another paper (see Althaus & Alizon) – admittedly, in connection with heterosexual groups – corroborates our common sense expectation by showing that the number of partners displays, if not a proportional, then at least a linear, relation  to number of sex acts. So can it really be the case that there is not a greater number of transmissions amongst the MSM population, given the greater number of partners? The authors evidently believe not.

Nevertheless, it would be interesting – as well as pertinent, I suspect, to the goals of the study – to have a more satisfying explanation of why, here, as elsewhere, common sense turns out to be wrong.




Global patterns in ante-natal syphilis prevalence: Why is sub-Saharan Africa different?

18 Jul, 16 | by Leslie Goode, Blogmaster

‘Can a meaningful pattern be discerned in the large variations in syphilis rates over the last century?’ This is the question addressed by a recent systematic review – Kenyon & Tsoumanis (K&T) – based on published data on ante-natal syphilis prevalence (ASP) from those countries for which that data is available since at least 1951.   This cutoff reduces the number of countries that qualify for inclusion, but allows more recent trends in the late twentieth, and early twenty-first, centuries, to be set against the background of the impact of the introduction of penicillin in the 1950s. A pattern emerges from the data, which K&T then to seek to explain by investigating its association with various potential variables through multivariate analysis: per capita GDP; circumcision practice; health expenditure; efficacy of diagnosis/treatment; geographical region.

The pattern itself is: in most parts of the world, a more or less steep decline following the introduction of penicillin – ultimately, by the 1990s, to below 1%, and by the 2000s, to below (massively below, in many cases) 0.5%; in sub-Saharan Africa alone, a decline plateauing out at around 6% up until the end of the twentieth century, when there is a further decline to just above 1.5%.  A limitation of the study is its concentration on eleven countries for which ASP data is available from before the days of penicillin, with only two of those countries being in sub-Saharan Africa (South Africa and Zimbabwe).  So far as concerns more recent evidence for ASP prevalence, the kind of rates that the authors give for SA and Zimbabwe seem, broadly, to be replicated in other countries of sub-Saharan Africa (Otieno-Nyunya & Kaiser/STIs (Kenya); Makasa & Sandoy/STIs (Zambia); Kirakoya-Samadoulougou & Nagot/STIs (Burkina-Faso);  Ardu-Sarkodie & Peeling/STIs (Ghana), and their rates for the other regions to be replicated in other non-sub-Saharan African settings (Cheng & Cai/STIs (China); Galdava & Domeika/STIs (Georgia) Thirumoorthy & Lim/STIs (Singapore)).

As for the explanation of this pattern, the authors find no association on multivariate analysis with any of their potential variables, save with residence in sub-Saharan Africa.  This is itself an interesting negative finding, and prompts the authors to consider other population-level correlations also included in the evidence reviewed – notably, with prevalence of HIV and HSV-2; ‘the populations that in the 1990s had high prevalences of syphilis and HSV-2 went on to have high HIV prevalences’.  The correlation with prevalence of HSV-2 is of particular interest because it is unlikely that the prevalence of the one infection could have influenced that of the other (see also: Hochberg & Dandona/STIs).  To K&T, it suggests the likely importance of ‘more connected sexual networks’ and ‘greater partner concurrency’ in explaining traditionally – and currently – high relative ASP levels in sub-Saharan Africa.  However, they refer to studies that contest this hypothesis, and emphasize the need for further research to elucidate the factors underpinning difference in syphilis rates – especially given the possibility that the successful use of ART in those countries may be accompanied by the re-establishment of former sexual networks.

UK National Health Service (NHS) kicks PrEP into the long grass

18 Jul, 16 | by Leslie Goode, Blogmaster

A recent BMJ editorial condemns the NHS position that it will not consider PrEP for direct NHS funding.  The decision was first communicated in an NHS statement issued in March, then confirmed by a review on 31st May, following reconsideration in response to objections raised by interested groups.  This brought to an end an eighteen-month process of discussion between Department of Health, doctors and patients groups, Public Health England and other stakeholders.  The NHS decision is currently under judicial review – which no doubt explains the timing of the BMJ editorial.

Advocates of PrEP argue that the NHS has powers under the Health and Social Care Act (2012) directly to commission services ‘prioritized for investment’, and that PrEP should qualify for consideration on this basis.  But the conclusion of the NHS is that PrEP does not qualify to be so considered because the Local Authorities Regulations (2013) clearly stipulate that commissioning for sexual health prevention is legally the responsibility of local government.

Technically, then, the argument turns on whether the NHS can commission for PrEP directly, given that PrEP is a form of sexual health prevention. Needless to say, in the eyes of the advocates of PrEP, this is a mere technicality invoked by the NHS in order to shirk its responsibilities.  The NHS statements also include the proposal to work with local government authorities on exploring how they should go about commissioning PrEP services most effectively, and to dedicate £2m to the establishment of local pilots.  The problem here is that local authorities, having lately had £200m shaved off their funding for sexual health services, are presumably not in a hurry to pick up the tab.

So what about the case for PrEP? As regards effectiveness for high-risk MSM populations, PrEP has emerged with flying colours from recent trials, including the UK PROUD  study (PrEP Highly Effective/STIs/blog; PROUD/STIs/blog) and trials with similar populations undertaken in France (IPERGAY) and California (Volk & Hare).  Cost effectiveness, however, is another matter – and here PrEP has failed to make the grade.  Recent studies have shown that in the UK PrEP is not even borderline cost-effective without substantial reductions in the cost of the drugs (Cambiano & Phillips/STIs; PrEP Highly Effective/STIs/blog; PrEP cost effectiveness study). And, of course, even cost-effectiveness is not the same as affordability.  When it is borne in mind how much in the way of demonstrably very cost effective services have recently been rendered unaffordable by government cuts (Unprotected Nation/Report), the case for PrEP in the present climate does not look strong.

Mathematical models say: switching to HPV nonavalent vaccine brings cost benefits.

20 Jun, 16 | by Leslie Goode, Blogmaster

STI journal issues of nearly a decade ago, when HPV vaccination was a relatively new thing, hosted a discussion on the issue of which vaccine to choose. The choice at that time, readers will remember, was between GSK’s Cervarix 2vHPV and Merck’s Gardasil 4vHPV (Morris/STIs)*.  Now, the introduction of a third alternative, Gardasil (9vHPV), seems to have fuelled a similar burst of activity amongst mathematical modellers – at least in the US, where the new vaccine was licensed in 2014.

Gardasil 9vHPV elicits immunity to nine oncogenic (i.e. associated with cancer) serotypes – i.e. five more serotypes than Gardasil 4vHPV, and seven more than Cervatrix 2vHPV.  The nonavalent vaccine (9vHPV) is expected to extend protection from >66% to 80% of cervical cancers.  It will also, it should not be forgotten, have some benefit in preventing HPV-related oropharygneal cancers (Field and Lechner/STIs).  However, Gardasil 9vHPV is approximately $13 per dose more expensive than Gardasil 4vHPV, and $18 more expensive than Cervatrix 2vHPV.  In 2015 the US Centers for Disease Control and Prevention (CDC) recommended vaccination with any of the three alternatives for females aged 9-26yrs, and with 4vHPV or 9vHPV for males aged 11-21yrs.

Once again, then, the question of the relative cost-effectiveness of HPV vaccines raises its head – this time in the US, and in connection with a possible switch from 4vHPV and 2vHPV to 9HPV as the vaccine of choice. Mathematical modellers in the US have risen to the challenge in at least two recent studies.  Brisson & Markowitz conclude that making the switch would be cost-effective ‘under most scenarios’ (Chesson & Saraiya/STIs; Brisson & Markowitz).  Now, Durham and Galvani (D&G), in another US modelling study, have reached the same conclusion.  Not content, however, with a response for current levels of vaccination coverage, they also consider the impact on cost-effectiveness of raising national coverage with 9vHPV to higher levels.  This requires them to take into account the effect of herd-immunity, which ensures that returns on investment diminish to the extent that higher levels of coverage have already been achieved.  They also consider the relative cost-effectiveness of distributing the investment in 9vHPV vaccination in such a way as to bring up the vaccination levels in states where it is low (e.g. Arkansas, Missisipi, Missouri, Kansas) towards the levels already achieved in other states (e.g. Illinois, Montana, N. Carolina, Washington DC), as against that of an even distribution.  (At present, state vaccination rates vary between 20-57% for females, and between 9-43% for males – though inter-state migration rates are such that 29-84% of the long-term health benefits of vaccination will be realized by beyond the boundaries of the state where vaccination took place).

The findings of the study are as follows.  9vHPV is cost-effective – as compared with the alternatives – at any level of coverage.  Comprehensively switching to 9vHPV would yield the same benefit as raising levels of coverage with existing vaccines across the population of the US by 11%.  Second, assuming a comprehensive switch to 9vHPV: a national increase in coverage of 10% would show an incremental cost-effectiveness ratio (ICER) corresponding to a willingness to pay (WTP) of $40,000 per QALY, and increases of 20%, or 40%, ICERs equivalent to WTPs of $53,000 and $106,000, respectively.  Finally, the figure of $40,000 WPT per QALY given above represents only an average, since, in practice, the cost-benefit of an increase of 10% in coverage would differ widely between states with low current levels of coverage, like Arkansas, where the cost-benefit would be around $13,500, and states with high levels, like California, where it would be around $56,400. The authors therefore advocate focussing the investment needed to achieve increases in coverage on states that currently have low levels of coverage.

  • a previous version of this blog mistakenly mistakenly gave the names of the manufacturers of Gardasil and Cervarix as GSK and Merck respectively.  The mistake has recently been brought to our attention, and the manufacturers as given in the emended blog (23.6.16) are the correct ones. (Blogmaster)

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