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7 Oct 2016

#Postimmunisation #monitoring of #HPV #vaccine-induced #seroprevalence in #England 2010 to 2013 (@PHE_uk, abstract)


Title: #Postimmunisation #monitoring of #HPV #vaccine-induced #seroprevalence in #England 2010 to 2013.

Subject: Huma Papilloma Virus, seroprevalence survey, England.

Source: Public Health England, full PDF document: (LINK). Abstract.

Code: [     ]


Infection report - Volume 10 - Number 34 - Published on: 7 October 2016 - HIV-STIs

Post-immunisation monitoring of HPV vaccine-induced seroprevalence in England 2010 to 2013



  • Seroconversion occurs following an estimated 50-70% of incident natural human papillomavirus (HPV) infections in women [1-4] and natural infection often elicits only a weak antibody response.
  • Conversely, vaccination induces seroconversion in ~100% of HPV-na├»ve recipients and generally results in far higher antibody concentrations than those following natural infection [5,6].
  • As such, serological assays which provide a quantitative measure of the level of HPV type-specific antibodies can be used to estimate HPV vaccination coverage.
  • Public Health England (PHE)’s monitoring of HPV seroprevalence (as part of work to monitor and evaluate the National HPV Immunisation Programme) has begun with a study of young women in the first birth cohorts to be offered HPV immunisation, primarily to compare vaccineinduced seroprevalence to nationally reported coverage data.
  • The first results from this surveillance have been published previously with data from 2,146 specimens collected between 2010 and 2011 [7].
  • We report here updated findings with results from 3,772 specimens collected up to 2013.



  • Residual serum specimens were collected for 15-19 year old females from the PHE Seroepidemiology Unit (SEU).
  • SEU specimens are collected from individuals attending for microbiological and/or biochemical tests.
  • Serum samples were submitted with data on gender, age at collection and year of collection from fourteen laboratories in England.
  • Laboratories were asked to identify, if possible, any specimens collected via Genitourinary (GU) Medicine clinics (defined as No, Yes or Not known).
  • Specimens collected from 2010 to 2013 are included in this analysis.
  • Where date of birth was available, this was used to generate the age and calendar year that HPV vaccination would have been offered: this was available for 2355/3772 (62.4%) of women.
  • For the remainder, with age in years available, likely year of eligibility for HPV vaccination was estimated.
  • Specimens collected in January-March following the due date of first vaccine dose were excluded in order to study seroprevalence after, not during, the scheduled full course of vaccination.
  • Specimens were tested for antibodies to HPV types 16 and 18 using a type-specific ELISA.
  • Testing was performed at the PHE Vaccine Evaluation Unit (VEU), Manchester. Specimens were considered to be seropositive above cut-offs determined previously with this assay: 19 and 18 ELISA units per millilitre (EU/mL) for HPV 16 and 18, respectively.
  • Methods to determine vaccine-induced seropositivity were as previously described [7]. In brief, each result was classified as “low”, “moderate” or “high” based on the concentration of HPV antibodies for HPV16 and HPV18.
  • Specimens were then categorised as (i) “probable” vaccineinduced seropositivity if seropositive for both types with high concentration for at least one type or moderate concentrations for both types, (ii) “probable” natural infection if seropositive for one type only, (iii) “possible” natural infection or vaccine induced seropositivity if low seropositivity for both types or low seropositivity for one type and moderate for the other.
  • Antibody concentrations are presented as geometric mean concentrations (GMCs) among seropositive specimens. Routinely published data on HPV vaccine coverage in England has been reported by academic year.
  • To compare these data with seroprevalence we estimated coverage by year of age and calendar year.



  • A total of 4,045 specimens had a valid result for type-specific HPV antibodies for both HPV types 16 and 18.
  • Excluding 323 samples which were collected in the January to March of the year following the due date of first vaccine dose; 3,722 specimens were included in this analysis (1205, 941, 952 and 674 collected in 2010, 2011, 2012 and 2013, respectively).
  • The mean age of women providing a specimen was 17.8 years (SD 1.42 years).
  • Overall, just under one-third (32.4%) of all specimens were identified as coming from a GU setting although this was not known for the majority of other specimens (64.1%): specimens from a known non-GU setting had higher seroprevalence (p=0.01 for vaccine-induced seropositivity).
  • Table 1 shows the demographics of all eligible women alongside the proportion seropositive for at least one HPV type.
  • A total of 69.9% (2,638/3,772) of specimens were seropositive for both types HPV16 and HPV18.
  • Seropositivity for HPV16 only and for HPV18 only was found in 4.4% (165) and 1.5% (58) of specimens respectively (table 2; figure 1).
  • Antibody concentrations were generally far higher for specimens seropositive for both HPV types than amongst those seropositive for only one type (median 2017.5 EU/ml vs 70 EU/ml for HPV16 and 804.5 EU/ml vs 59 EU/ml for HPV18) (table 2).
  • Vaccine-induced seropositivity was highest in the younger ages with higher expected vaccine coverage (table 3).
  • This finding was consistent in sub-analyses by region (data not shown).
  • The overall proportion of females with probable vaccine-induced seropositivity was 66% (2,472/3,772) and 4.4% (166/3,772) with possible natural infection or possible vaccine-induced seropositivity.
  • The proportion of females with vaccine-induced seropositivity was slightly lower than the reported three-dose coverage for 15 and 16 year olds but higher at older ages (table 3 and figure 2).



  • These data add to previous data confirming high coverage of HPV vaccination in England but with some potential under-reporting of vaccination of older females and/or a potential protective effect of receiving fewer than three doses.
  • This updated analysis provides data on antibody responses up to five years post-vaccination.
  • Whilst there is some evidence of slight declines in antibody concentrations over time since vaccination, these still remain far higher than antibody concentrations following a natural infection.



David Mesher, Richard Pebody, Kate Soldan, Joanne White: Centre for Infectious Disease Surveillance and Control, National Infection Service, Public Health England, 61 Colindale Avenue, London, NW9 5EQ.  Ray Borrow, Jamie Findlow, Ezra Linley, Rosalind Warrington: Vaccine Evaluation Unit, Public Health England, Manchester Medical Microbiology Partnership, M13 9WL.



Keywords: UK; Updates; HPV; Vaccines; England; Research.