Publications by authors named "Simon Beddows"

62 Publications

Post-vaccination HPV seroprevalence among female sexual health clinic attenders in England.

Vaccine 2021 Jul 12;39(30):4210-4218. Epub 2021 Jun 12.

Blood Safety, Hepatitis, Sexually Transmitted Infections (STI) and HIV Service, Public Health England, London, UK.

Background: The National HPV Immunisation Programme was introduced in England in September 2008 using the HPV16/18 bivalent vaccine. We conducted serological surveillance to explore vaccination coverage levels. We also conducted a case-control study to investigate a hypothesised cross-protective effect of the HPV16/18 vaccine against genital warts.

Methods: Residual serum specimens from 16 to 20 year-old women attending six specialist sexual health services (SSHS) between 2011 and 2015 in England were tested for antibodies against HPV16 and HPV18 using a virus-like particle (VLP)-based multiplex serology assay. Patients were classified as having vaccine-induced seropositivity if they were seropositive for both HPV types and either had high antibody levels for at least one HPV type, or moderately high levels for both HPV types. Differences in vaccine-induced seropositivity by patient characteristics were investigated using logistic regression. Vaccine-induced seropositivity was then compared for patients with genital warts (cases) and matched patients without (controls).

Results: Of 3,973 serum specimens collected, 3,870 (97.4%) had a valid result. The proportion of women with vaccine-induced seropositivity decreased with age (from 78.1% in 16-year-olds to 52.6% in 20-year-olds). Vaccine-induced seropositivity was lower among women born outside the UK, from more deprived areas and with a history of chlamydia diagnosis. A difference in uptake by ethnic group was also seen but this was largely confounded by differences in deprivation and country of birth. Among 537 cases and 1,515 controls, there was little evidence of a protective effect of the bivalent HPV vaccine against genital warts (adjusted odds ratio 0.93; 95% CI: 0.74-1.18).

Discussion: Vaccine-induced seropositivity in this high-risk population was in line with vaccination coverage in the general population although was lower in some at-risk sub-groups. This study does not provide evidence to support a cross-protective effect of the HPV16/18 vaccine against genital warts.
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http://dx.doi.org/10.1016/j.vaccine.2021.05.018DOI Listing
July 2021

HPV16 and HPV18 seropositivity and DNA detection among men who have sex with men: a cross-sectional study conducted in a sexual health clinic in London.

Sex Transm Infect 2021 Aug 23;97(5):382-386. Epub 2020 Dec 23.

Institute for Global Health, University College London, London, UK

Objectives: Men who have sex with men (MSM) have an increased risk of human papillomavirus (HPV) infection and related diseases compared with men who have sex exclusively with women. From April 2018, there has been a phased roll-out of HPV vaccination offered to MSM aged up to 45 years old who are attending sexual health clinics and HIV clinics in England. The vaccine is most effective if delivered prior to HPV infection. We estimated the proportion of MSM with no current vaccine-type infection and no serological evidence of prior infection, in a study undertaken prior to vaccine introduction.

Methods: We conducted a cross-sectional study among 484 MSM aged 18-40 years old who attended a sexual health clinic in London between 2010 and 2012. We estimated the prevalence of current and past infection by testing for HPV DNA in anogenital samples and for serum antibodies to HPV16 and HPV18.

Results: The median age was 30 years (IQR 25-35). The prevalence of HPV16 and HPV18 DNA was 13.2% and 6.2%, respectively. Seropositivity for HPV16 and HPV18 was 28.5% and 17.1%, respectively, with 11.4% seropositive for both types. Seropositivity for the same HPV type was strongly associated with anogenital DNA detection. 279 MSM (57.6%) tested negative for both HPV16 and HPV18 serology and were DNA negative for these two types; only 5 MSM (1.0%) were seropositive and DNA positive for both HPV types.

Conclusions: This is the first study to determine both the prevalence of HPV DNA in anogenital samples and HPV seroprevalence among MSM attending a sexual health clinic in the UK. Over half of MSM in this study had no evidence of a previous or current infection with either of the high-risk HPV types included in the quadrivalent vaccine, which supports the rationale for opportunistic HPV vaccination of MSM attending sexual health clinics.
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http://dx.doi.org/10.1136/sextrans-2020-054726DOI Listing
August 2021

Performance of human papillomavirus DNA detection in residual specimens taken for and nucleic acid amplification testing in men who have sex with men.

Sex Transm Infect 2020 Dec 16. Epub 2020 Dec 16.

Centre for Clinical Research in Infection and Sexual Health, University College London, London, UK.

Objectives: Rectal swab specimens, either alone or pooled with first-void urine (FVU) and pharyngeal swab specimens, are used to test for (CT) and (NG) infection in men who have sex with men (MSM). Following introduction of human papillomavirus (HPV) vaccination for MSM attending UK sexual health services (SHSs), HPV testing of residual CT/NG test specimens has been proposed to monitor HPV prevalence in this population. Performance of HPV detection in such specimens has not been evaluated previously.

Methods: MSM attending a UK SHS provided three specimens: (1) rectal swab for CT/NG, (2) pooled rectal/pharyngeal/FVU specimen for CT/NG and (3) dedicated anal swab for HPV. Specimen 3 and residual material from specimens 1 and 2 were tested for type-specific HPV DNA. HPV detection was by an in-house multiplex PCR and luminex-based genotyping assay.

Results: A total of 129 MSM were recruited with a mean age of 38.1 years; 24% were HIV-positive. Of the 129 MSM, 92 (71%) had any type-specific HPV DNA in ≥1 specimen; 80 (62%) had high risk (HR) HPV. Of 123 participants with sufficient residual pooled and dedicated specimens, 70 (56.9%) had detectable HPV on both, and 40 (32.5%) were negative on both; overall concordance was 89% (95% CI 83% to 94%), and kappa statistic was 0.78 (95% CI 0.66 to 0.89). Pooled samples had a 4.1% (95% CI -1.9% to 10.0%) higher test positivity rate than dedicated samples.Of 125 participants with sufficient residual rectal and specimens, 74 (59.2%) had detectable HPV on both, and 36 (28.8%) were negative on both; overall concordance was 88% (95% CI 81% to 93%), and kappa statistic was 0.74 (95% CI 0.61 to 0.86). Residual rectal samples had 5.6% (95%CI -0.6% to 11.8%) higher test positivity than dedicated samples.

Conclusions: We observed high concordance between the dedicated and residual STI test specimens. Our data support the strategy of testing residual specimens for HPV prevalence monitoring in MSM to evaluate the impact of the targeted vaccination programme.
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http://dx.doi.org/10.1136/sextrans-2020-054702DOI Listing
December 2020

Comprehensive Assessment of the Antigenic Impact of Human Papillomavirus Lineage Variation on Recognition by Neutralizing Monoclonal Antibodies Raised against Lineage A Major Capsid Proteins of Vaccine-Related Genotypes.

J Virol 2020 11 23;94(24). Epub 2020 Nov 23.

Virus Reference Department, Public Health England, London, UK

Human papillomavirus (HPV) is the causative agent of cervical and other epithelial cancers. Naturally occurring variants of HPV have been classified into lineages and sublineages based on their whole-genome sequences, but little is known about the impact of this diversity on the structure and function of viral gene products. The HPV capsid is an icosahedral lattice comprising 72 pentamers of the major capsid protein (L1) and the associated minor capsid protein (L2). We investigated the potential impact of this genome variation on the capsid antigenicity of lineage and sublineage variants of seven vaccine-relevant, oncogenic HPV genotypes by using a large panel of monoclonal antibodies (MAbs) raised against the L1 proteins of lineage A antigens. Each genotype had at least one variant that displayed a ≥4-fold reduced neutralizing antibody sensitivity against at least one MAb, demonstrating that naturally occurring variation can affect one or more functional antigenic determinants on the HPV capsid. For HPV16, HPV18, HPV31, and HPV45, the overall impact was of a low magnitude. For HPV33 (sublineages A2 and A3 and lineages B and C), HPV52 (lineage D), and HPV58 (lineage C), however, variant residues in the indicated lineages and sublineages reduced their sensitivity to neutralization by all MAbs by up to 1,000-fold, suggesting the presence of key antigenic determinants on the surface of these capsids. These determinants were resolved further by site-directed mutagenesis. These data improve our understanding of the impact of naturally occurring variation on the antigenicity of the HPV capsid of vaccine-relevant oncogenic HPV genotypes. Human papillomavirus (HPV) is the causative agent of cervical and some other epithelial cancers. HPV vaccines generate functional (neutralizing) antibodies that target the virus particles (or capsids) of the most common HPV cancer-causing genotypes. Each genotype comprises variant forms that have arisen over millennia and which include changes within the capsid proteins. In this study, we explored the potential for these naturally occurring variant capsids to impact recognition by neutralizing monoclonal antibodies. All genotypes included at least one variant form that exhibited reduced recognition by at least one antibody, with some genotypes affected more than others. These data highlight the impact of naturally occurring variation on the structure of the HPV capsid proteins of vaccine-relevant oncogenic HPV genotypes.
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http://dx.doi.org/10.1128/JVI.01236-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925199PMC
November 2020

Human papillomavirus (HPV) vaccination and oropharyngeal HPV in ethnically diverse, sexually active adolescents: community-based cross-sectional study.

Sex Transm Infect 2020 Sep 3. Epub 2020 Sep 3.

Population Health Research Institute, St George's University of London, London, UK

Objectives: Oropharyngeal squamous cell carcinoma is the most common human papillomavirus (HPV)-associated cancer in the UK, but little is known about the prevalence of oropharyngeal HPV in sexually active teenagers. We investigated reported HPV vaccination coverage (in females) and prevalence of oropharyngeal HPV in sexually active students attending six technical colleges in London, UK.

Methods: In 2017, we obtained mouthwash samples and questionnaires from male and female students taking part in the 'Test n Treat' chlamydia screening trial. Samples were subjected to HPV genotyping.

Results: Of 232 participants approached, 202 (87%) provided a mouthwash sample and questionnaire. Participants' median age was 17 years and 47% were male. Most (73%) were from black and minority ethnic groups, 64% gave a history of oral sex, 52% reported having a new sexual partner in the past 6 months, 33% smoked cigarettes, 5.9% had concurrent genitourinary infection and 1.5% and 5.0% were gay or bisexual. Only 47% (50/107) of females reported being vaccinated against HPV 16/18, of whom 74% had received ≥2 injections. HPV genotyping showed three mouthwash samples (1.5%, 95% CI 0.3% to 4.3%) were positive for possible high-risk human papillomavirus (HR-HPV), one (0.5%, 0.0% to 2.7%) for low-risk HPV 6/11, but none (0.0%, 0.0% to 1.8%) for HR-HPV. Four samples (2.0%, 0.5% to 5.0%) were positive for HPV16 using a HPV16 type-specific quantitative PCR, but these were at a very low copy number and considered essentially negative.

Conclusions: Despite the high prevalence of oral sex and genitourinary chlamydia and low prevalence of HPV vaccination, the prevalence of oropharyngeal HR-HPV in these adolescents was negligible.
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http://dx.doi.org/10.1136/sextrans-2020-054428DOI Listing
September 2020

Antimicrobial resistance in sampled from the British general population.

Sex Transm Infect 2020 09 10;96(6):464-468. Epub 2020 Jan 10.

Centre for Molecular Epidemiology and Translational Research, Institute for Global Health, UCL, London, United Kingdom

Background: is a common sexually transmitted infection. Treatment guidelines focus on those with symptoms and sexual contacts, generally with regimens including doxycycline and/or azithromycin as first-line and moxifloxacin as second-line treatment. We investigated the prevalence of antimicrobial resistance (AMR)-conferring mutations in among the sexually-active British general population.

Methods: The third national survey of sexual attitudes and lifestyles (Natsal-3) is a probability sample survey of 15 162 men and women aged 16-74 years in Britain conducted during 2010-12. Urine test results for were available for 4507 participants aged 16-44 years reporting 1 lifetime sexual partner. In this study, we sequenced regions of the 23S rRNA and genes to detect known genotypic determinants for resistance to macrolides and fluoroquinolones respectively.

Results: 94% (66/70) of specimens were re-confirmed as positive, with successful sequencing in 85% (56/66) for 23S rRNA and 92% (61/66) for genes. Mutations in 23S rRNA gene (position A2058/A2059) were detected in 16.1% (95%CI: 8.6% to 27.8%) and in (encoding D87N/D87Y) in 3.3% (0.9%-11.2%). Macrolide resistance was more likely in participants reporting STI diagnoses (past 5 years) (44.4% (18.9%-73.3%) vs 10.6% (4.6%-22.6%); p=0.029) or sexual health clinic attendance (past year) (43.8% (23.1%-66.8%) vs 5.0% (1.4%-16.5%); p=0.001). All 11 participants with AMR-conferring mutations had attended sexual health clinics (past 5 years), but none reported recent symptoms.

Conclusions: This study highlights challenges in management and control. Macrolide resistance was present in one in six specimens from the general population in 2010-2012, but no participants with AMR reported symptoms. Given anticipated increases in diagnostic testing, new strategies including novel antimicrobials, AMR-guided therapy, and surveillance of AMR and treatment failure are recommended.
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http://dx.doi.org/10.1136/sextrans-2019-054129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476295PMC
September 2020

Sensitivity of Human Papillomavirus (HPV) Lineage and Sublineage Variant Pseudoviruses to Neutralization by Nonavalent Vaccine Antibodies.

J Infect Dis 2019 11;220(12):1940-1945

Virus Reference Department, Public Health England, London, United Kingdom.

Natural variants of human papillomavirus (HPV) are classified into lineages and sublineages based upon whole-genome sequence, but the impact of diversity on protein function is unclear. We investigated the susceptibility of 3-8 representative pseudovirus variants of HPV16, HPV18, HPV31, HPV33, HPV45, HPV52, and HPV58 to neutralization by nonavalent vaccine (Gardasil®9) sera. Many variants demonstrated significant differences in neutralization sensitivity from their consensus A/A1 variant but these were of a low magnitude. HPV52 D and HPV58 C variants exhibited >4-fold reduced sensitivities compared to their consensus A/A1 variant and should be considered distinct serotypes with respect to nonavalent vaccine-induced immunity.
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http://dx.doi.org/10.1093/infdis/jiz401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834066PMC
November 2019

Durability of the neutralizing antibody response to vaccine and non-vaccine HPV types 7 years following immunization with either Cervarix® or Gardasil® vaccine.

Vaccine 2019 04 27;37(18):2455-2462. Epub 2019 Mar 27.

Virus Reference Department, Public Health England, London, UK. Electronic address:

Bivalent (Cervarix®) and quadrivalent (Gardasil®) Human Papillomavirus (HPV) vaccines demonstrate remarkable efficacy against the targeted genotypes, HPV16 and HPV18, but also a degree of cross-protection against non-vaccine incorporated genotypes, HPV31 and HPV45. These outcomes seem to be supported by observations that the HPV vaccines induce high titer neutralizing antibodies against vaccine types and lower responses against non-vaccine types. Few data are available on the robustness of the immune response against non-vaccine types. We examined the durability of vaccine and non-vaccine antibody responses in a follow up of a head-to-head study of 12-15 year old girls initially randomized to receive three doses of Cervarix® or Gardasil® vaccine. Neutralizing antibodies against both vaccine and non-vaccine types remained detectable up to 7 years following initial vaccination and a mixed effects model was used to predict the decline in antibody titers over a 15 year period. The decline in vaccine and non-vaccine type neutralizing antibody titers over the study period was estimated to be 30% every 5-7 years, with Cervarix® antibody titers expected to remain 3-4 fold higher than Gardasil® antibody titers over the long term. The antibody decline rates in those with an initial response to non-vaccine types were similar to that of vaccine types and are predicted to remain detectable for many years. Empirical data on the breadth, magnitude, specificity and durability of the immune response elicited by the HPV vaccines contribute to improving the evidence base supporting this important public health intervention. Original trial: ClinicalTrials.gov NCT00956553.
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http://dx.doi.org/10.1016/j.vaccine.2019.03.052DOI Listing
April 2019

Epidemiology of genital warts in the British population: implications for HPV vaccination programmes.

Sex Transm Infect 2019 08 5;95(5):386-390. Epub 2019 Feb 5.

Mortimer Market Centre, Institute for Global Health, University College London, London, UK.

Objectives: To estimate the prevalence of, and describe risk factors for, genital warts (GWs) in the British population, following the introduction of the bivalent (human papillomavirus (HPV)-16/18) vaccination programme in girls, and prior to the switch to quadrivalent (HPV-6/11/16/18) vaccine (offering direct protection against GWs) and compare this with GW diagnoses in the prevaccination era.

Methods: Natsal-3, a probability sample survey in Britain, conducted in 2010-2012, interviewed 9902 men and women aged 16-44. Natsal-2, conducted in 1999-2001, surveyed 11 161 men and women aged 16-44. Both surveys collected data on sexual behaviour and sexually transmitted infection diagnoses using computer-assisted interview methods.

Results: In Natsal-3, 3.8% and 4.6% of sexually experienced men and women reported ever having a diagnosis of GWs, with 1.3% of men and 1.7% of woman reporting a GWs diagnosis in the past 5 years. GWs were strongly associated with increasing partner numbers and condomless sex. Diagnoses were more frequent in men who have sex with men (MSM) (11.6% ever, 3.3% past 5 years) and in women reporting sex with women (10.8% ever, 3.6% past 5 years). In the age group who were eligible for vaccination at the time of Natsal-3 (16-20 years), a similar proportion of same-aged women reported a history of GWs in Natsal-2 (1.9%, 1.1-3.4) and Natsal-3 (2.6%, 1.5-4.4).

Conclusions: These data provide essential parameters for mathematical models that inform cost-effectiveness analyses of HPV vaccination programmes. There was no evidence of population protection against GWs conferred by the bivalent vaccine. Even with vaccination of adolescent boys, vaccination should be offered to MSM attending sexual health clinics.
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http://dx.doi.org/10.1136/sextrans-2018-053786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678036PMC
August 2019

Impact of naturally occurring variation in the human papillomavirus 52 capsid proteins on recognition by type-specific neutralising antibodies.

J Gen Virol 2019 02 18;100(2):237-245. Epub 2019 Jan 18.

1​Virus Reference Department, Public Health England, London, UK.

We investigated the impact of naturally occurring variation within the major (L1) and minor (L2) capsid proteins on the antigenicity of human papillomavirus (HPV) type 52 (HPV52). L1L2 pseudoviruses (PsVs) representing HPV52 lineage and sublineage variants A1, A2, B1, B2, C and D were created and tested against serum from naturally infected individuals, preclinical antisera raised against HPV52 A1 and D virus-like particles (VLPs) and neutralising monoclonal antibodies (MAbs) raised against HPV52 A1 VLP. HPV52 lineage D PsV displayed a median 3.1 (inter-quartile range 2.0-5.6) fold lower sensitivity to antibodies elicited following natural infection with, where data were available, HPV52 lineage A. HPV52 lineage variation had a greater impact on neutralisation sensitivity to pre-clinical antisera and MAbs. Chimeric HPV52 A1 and D PsV were created which identified variant residues in the FG (Q281K) and HI (K354T, S357D) loops as being primarily responsible for the reported differential sensitivities. Homology models of the HPV52 L1 pentamer were generated which permitted mapping these residues to a small cluster on the outer rim of the surface exposed pentameric L1 protein. These data contribute to our understanding of HPV L1 variant antigenicity and may have implications for seroprevalence or vaccine immunity studies based upon HPV52 antigens.
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http://dx.doi.org/10.1099/jgv.0.001213DOI Listing
February 2019

The Impact of the National HPV Vaccination Program in England Using the Bivalent HPV Vaccine: Surveillance of Type-Specific HPV in Young Females, 2010-2016.

J Infect Dis 2018 08;218(6):911-921

HIV and STI Department, Centre for Infectious Disease Surveillance and Control, London, United Kingdom.

Background: The national human papillomavirus (HPV) immunization program was introduced in England in September 2008 using the bivalent vaccine.

Methods: We collected residual vulva-vaginal swab specimens from 16 to 24-year-old women attending for chlamydia screening between 2010 and 2016 and tested for HPV DNA. We compared changes in type-specific (vaccine and nonvaccine) HPV prevalence over time and association with vaccination coverage. For women with known vaccination status, vaccine effectiveness was estimated.

Results: HPV DNA testing was completed for 15459 specimens. Prevalence of HPV16/18 decreased between 2010/2011 and 2016 from 8.2% to 1.6% in 16-18 year olds and from 14.0% to 1.6% in 19-21 year olds. Declines were also seen for HPV31/33/45 (6.5% to 0.6% for 16-18 year olds and 8.6% to 2.6% for 19-21 year olds). Vaccine effectiveness for HPV16/18 was 82.0% (95% confidence interval [CI], 60.6%-91.8%) and for HPV31/33/45 was 48.7% (95% CI, 20.8%-66.8%). Prevalence of HPV16/18 was compared to findings in 2007-2008 (prevaccination) and to predictions from Public Health England's mathematical model.

Discussion: Eight years after the introduction of a national HPV vaccination program, substantial declines have occurred in HPV16/18 and HPV31/33/45. The prevalence of other high-risk HPV types has not changed.
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http://dx.doi.org/10.1093/infdis/jiy249DOI Listing
August 2018

Impact of Naturally Occurring Variation in the Human Papillomavirus 58 Capsid Proteins on Recognition by Type-Specific Neutralizing Antibodies.

J Infect Dis 2018 10;218(10):1611-1621

Virus Reference Department, Public Health England, London, United Kingdom.

Background: Naturally occurring variants of human papillomavirus (HPV) 58 have been defined as lineages and sublineages but little is known about the impact of this diversity on protein function. We investigated the impact of variation within the major (L1) and minor (L2) capsid proteins of HPV58 on susceptibility to neutralizing antibodies.

Methods: Pseudovirus (PsV) representing A1, A2, A3, B1, B2, C, D1, and D2 variants were evaluated for their susceptibility to antibodies elicited during natural infection, preclinical antisera generated against virus-like particles, and monoclonal antibodies (MAbs).

Results: Lineage C PsV demonstrated a decreased sensitivity to antibodies raised against lineage A antigens. Exchange of the DE, FG, and/or HI loops between sublineage A1 and lineage C demonstrated that residues within all 3 loops were essential for the differential sensitivity to natural infection antibodies, with slightly different requirements for the animal antisera and MAbs. Comparison between the HPV58 A1 L1 pentamer crystal structure and an HPV58 C homology model indicated that these differences in neutralization sensitivity were likely due to subtle epitope sequence changes rather that major structural alterations.

Conclusions: These data improve our understanding of the impact of natural variation on HPV58 capsid antigenicity and raise the possibility of lineage-specific serotypes.
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http://dx.doi.org/10.1093/infdis/jiy354DOI Listing
October 2018

Evaluation of Dried Blood Spots and Oral Fluids as Alternatives to Serum for Human Papillomavirus Antibody Surveillance.

mSphere 2018 May-Jun;3(3). Epub 2018 May 9.

Virus Reference Department, Public Health England, London, United Kingdom

Human papillomavirus (HPV) vaccination elicits high-titer genotype-specific antibody responses that are associated with a reduced risk of cervical disease caused by vaccine-incorporated genotypes. Our objective was to evaluate dried blood spots (DBSs) and oral mucosal transudate (OMT) as alternative samples to serum to confirm HPV vaccine antibody status. A study was carried out to evaluate the feasibility of detecting HPV16 and HPV18 antibodies in OMT, DBSs, and sera among women who self-reported being unvaccinated or fully vaccinated with the HPV vaccine. Serum had the highest sensitivity (100%) for detection of antibodies against both HPV16 and HPV18 but the lowest specificity, due to the detection of natural infection antibodies in 16% of unvaccinated women. Conversely, DBSs and OMT had lower sensitivity (96% and 82%, respectively) but high specificity (98%). We confirmed that these antibodies were functional (i.e., neutralizing) and that their detection was quantitatively reproducible and well correlated between sample types when normalized to IgG content. DBSs and OMT are appropriate alternative sample types for HPV vaccine surveillance. These alternative sample types warrant consideration for the purposes of cervical screening, diagnosis, and management, but more work will be needed to establish the stringent parameters required for such application. Human papillomavirus (HPV) is the causative agent of cervical and other anogenital cancers. HPV vaccination, primarily targeted at young girls before the age of sexual debut, is starting to demonstrate population-level declines in HPV infection and early disease associated with vaccine-incorporated genotypes. Monitoring young women for vaccine-specific antibody is important for vaccine surveillance and may be useful as an adjunct test within a cervical screening context. We evaluated serum, dried blood spots, and oral fluid as potential samples for such applications and report robust measures of diagnostic accuracy. This is the first time a direct comparison of alternative sample types has been made between vaccinated and unvaccinated women for the detection and quantitation of HPV antibodies.
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http://dx.doi.org/10.1128/mSphere.00043-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956145PMC
October 2018

Immunogenicity of HPV prophylactic vaccines: Serology assays and their use in HPV vaccine evaluation and development.

Vaccine 2018 08 1;36(32 Pt A):4792-4799. Epub 2018 Feb 1.

Chronic Viral Diseases Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA. Electronic address:

When administered as standard three-dose schedules, the licensed HPV prophylactic vaccines have demonstrated extraordinary immunogenicity and efficacy. We summarize the immunogenicity of these licensed vaccines and the most commonly used serology assays, with a focus on key considerations for one-dose vaccine schedules. Although immune correlates of protection against infection are not entirely clear, both preclinical and clinical evidence point to neutralizing antibodies as the principal mechanism of protection. Thus, immunogenicity assessments in vaccine trials have focused on measurements of antibody responses to the vaccine. Non-inferiority of antibody responses after two doses of HPV vaccines separated by 6 months has been demonstrated and this evidence supported the recent WHO recommendations for two-dose vaccination schedules in both boys and girls 9-14 years of age. There is also some evidence suggesting that one dose of HPV vaccines may provide protection similar to the currently recommended two-dose regimens but robust data on efficacy and immunogenicity of one-dose vaccine schedules are lacking. In addition, immunogenicity has been assessed and reported using different methods, precluding direct comparison of results between different studies and vaccines. New head-to-head vaccine trials evaluating one-dose immunogenicity and efficacy have been initiated and an increase in the number of trials relying on immunobridging is anticipated. Therefore, standardized measurement and reporting of immunogenicity for the up to nine HPV types targeted by the current vaccines is now critical. Building on previous HPV serology assay standardization and harmonization efforts initiated by the WHO HPV LabNet in 2006, new secondary standards, critical reference reagents and testing guidelines will be generated as part of a new partnership to facilitate harmonization of the immunogenicity testing in new HPV vaccine trials.
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http://dx.doi.org/10.1016/j.vaccine.2017.11.089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050153PMC
August 2018

Impact of naturally occurring variation in the human papillomavirus (HPV) 33 capsid proteins on recognition by vaccine-induced cross-neutralizing antibodies.

J Gen Virol 2017 Jul 8;98(7):1755-1761. Epub 2017 Jul 8.

Virus Reference Department, Public Health England, London, UK.

We investigated naturally occurring variation within the major (L1) and minor (L2) capsid proteins of human papillomavirus (HPV) genotype 33. Pseudoviruses (PsV) representing HPV33 lineages A1, A2, A3, B and C exhibited comparable particle-to-infectivity ratios and morphology but demonstrated a decreased sensitivity (A2, A3, B and C) to cross-neutralization by HPV vaccine antibodies compared to the A1 sublineage. Chimeric PsVs demonstrated that these differences in sensitivity were due to polymorphisms in the L1 protein, with little or no influence from variation within the L2 protein. Site-directed mutagenesis of the L1 gene identified the DE loop residue 133 and the FG residue 266 as being critical for conferring this differential sensitivity. The use of HPV33 homology models based upon the HPV16 crystal structure suggested that they are likely to act independently on more than one antibody epitope. These data improve our understanding of the potential impact of natural capsid variation on recognition by vaccine antibodies.
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http://dx.doi.org/10.1099/jgv.0.000829DOI Listing
July 2017

Seropositivity to non-vaccine incorporated genotypes induced by the bivalent and quadrivalent HPV vaccines: A systematic review and meta-analysis.

Vaccine 2017 07 17;35(32):3922-3929. Epub 2017 Jun 17.

Virus Reference Department, Public Health England, London, UK. Electronic address:

Background: Human papillomavirus vaccines have demonstrated remarkable efficacy against persistent infection and disease associated with vaccine-incorporated genotypes and a degree of efficacy against some genetically related, non-vaccine-incorporated genotypes. The vaccines differ in the extent of cross-protection against these non-vaccine genotypes. Data supporting the role for neutralizing antibodies as a correlate or surrogate of cross-protection are lacking, as is a robust assessment of the seroconversion rates against these non-vaccine genotypes.

Methods: We performed a systematic review and meta-analysis of available data on vaccine-induced neutralizing antibody seropositivity to non-vaccine incorporated HPV genotypes.

Results: Of 304 articles screened, 9 were included in the analysis representing ca. 700 individuals. The pooled estimate for seropositivity against HPV31 for the bivalent vaccine (86%; 95%CI 78-91%) was higher than that for the quadrivalent vaccine (61%; 39-79%; p=0.011). The pooled estimate for seropositivity against HPV45 for the bivalent vaccine (50%; 37-64%) was also higher than that for the quadrivalent vaccine (16%; 6-36%; p=0.007). Seropositivity against HPV33, HPV52 and HPV58 were similar between the vaccines. Mean seropositivity rates across non-vaccine genotypes were positively associated with the corresponding vaccine efficacy data reported from vaccine trials.

Conclusions: These data improve our understanding of vaccine-induced functional antibody specificity against non-vaccine incorporated genotypes and may help to parameterize vaccine-impact models and improve patient management in a post-vaccine setting.
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http://dx.doi.org/10.1016/j.vaccine.2017.06.028DOI Listing
July 2017

Human papillomavirus (HPV) in young women in Britain: Population-based evidence of the effectiveness of the bivalent immunisation programme and burden of quadrivalent and 9-valent vaccine types.

Papillomavirus Res 2017 Jun;3:36-41

Research Department of Infection & Population Health, University College London, Mortimer Market Centre, London WC1E 6JB, UK. Electronic address:

Background: In 2008, the UK introduced an HPV immunisation programme in girls. Population-based prevalence estimates of bivalent (HPV-16/18), quadrivalent (HPV-6/11/16/18) and 9-valent (HPV-6/11/16/18/31/33/45/52/58) vaccine types, and comparison over time, are needed to monitor impact, evaluate effectiveness and guide decision-making on vaccination strategies.

Methods: The third National Survey of Sexual Attitudes and Lifestyles (Natsal-3) in 2010-12, tested urine for HPV from 2569 sexually-experienced women aged 16-44. We report type-specific HPV prevalence and compare results with 1798 women in Natsal-2 (1999-2001) using age-adjusted prevalence ratios (APR).

Findings: In Natsal-3, 4.2% of women aged 16-44y were positive for HPV-16/18 and 2.9% for HPV-6/11. In 16-20 year olds, 4.5%, 10.8% and 20.7% had at least one bivalent, quadrivalent or 9-valent vaccine type, respectively. Three-dose vaccine coverage was 52.0% in women aged 18-20y. In this age group, HPV-16/18 prevalence was lower in Natsal-3 than Natsal-2 (5.8% vs 11.2%; APR=0.48[95%CI: 0.24-0.93]), however, prevalences of HPV-6/11, HPV-31/33/45 and HPV-52/58 were unchanged. HPV-16/18 prevalence was also unchanged in women aged 21-44y (APR=0.85[0.61-1.19]).

Interpretation: These probability surveys provide evidence of the impact of the bivalent immunisation programme. Reductions were specific to HPV-16/18 and to the age group eligible for vaccination. However, substantial vaccine-preventable HPV remains.
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http://dx.doi.org/10.1016/j.pvr.2017.01.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462921PMC
June 2017

The DE and FG loops of the HPV major capsid protein contribute to the epitopes of vaccine-induced cross-neutralising antibodies.

Sci Rep 2016 12 22;6:39730. Epub 2016 Dec 22.

Virus Reference Department, Public Health England, London, UK.

The human papillomavirus (HPV) vaccines consist of major capsid protein (L1) virus-like particles (VLP) and are highly efficacious against the development of cervical cancer precursors attributable to oncogenic genotypes, HPV16 and HPV18. A degree of vaccine-induced cross-protection has also been demonstrated against genetically-related genotypes in the Alpha-7 (HPV18-like) and Alpha-9 (HPV16-like) species groups which is coincident with the detection of L1 cross-neutralising antibodies. In this study the L1 domains recognised by inter-genotype cross-neutralising antibodies were delineated. L1 crystallographic homology models predicted a degree of structural diversity between the L1 loops of HPV16 and the non-vaccine Alpha-9 genotypes. These structural predictions informed the design of chimeric pseudovirions with inter-genotype loop swaps which demonstrated that the L1 domains recognised by inter-genotype cross-neutralising antibodies comprise residues within the DE loop and the late region of the FG loop. These data contribute to our understanding of the L1 domains recognised by vaccine-induced cross-neutralising antibodies. Such specificities may play a critical role in vaccine-induced cross-protection.
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http://dx.doi.org/10.1038/srep39730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5177933PMC
December 2016

infection is uncommon in the British general population: implications for clinical testing and public health screening.

Sex Transm Infect 2018 05 29;94(3):226-229. Epub 2016 Sep 29.

Research Department of Infection and Population Health, University College London, London, UK.

Introduction: Variable use of new molecular assays, asymptomatic infections and a lack of population data mean that the population burden of is uncertain. We investigated the age-specific prevalence of within the sexually active British general population to inform testing strategies.

Methods: Britain's third National Survey of Sexual Attitudes and Lifestyle (Natsal-3) is a probability sample survey of 15 162 individuals aged 16-74 years, undertaken during 2010-2012. Urine from 4386 participants aged 16-44 years reporting ≥1 lifetime sexual partner was tested for using in-house real-time PCR.

Results: Urinary was detected in seven women and no men providing urine samples, giving a weighted prevalence estimate of 0.3% (95% CI 0.1% to 0.5%) in sexually experienced women aged 16-44 years. Of the seven women with detected, four were of black or mixed ethnicity (prevalence 2.7% (0.9% to 7.7%) in this group) and five reported recent partners of black or mixed ethnicity. Six of the women reported symptoms, and five reported sexual health clinic attendance in the past 5 years (prevalence in those reporting clinic attendance: 1.0% (0.4% to 2.3%)). The prevalence of a self-reported history of (past 5 years) was 0.1% (0.0% to 0.2%) in women and 0.0% (0.0% to 0.2%) in men aged 16-44 years.

Conclusions: Our British population prevalence estimates indicate that is a rare infection. These data support policies that restrict asymptomatic screening for and suggest deployment of molecular tests should be focused within clinical settings and guided by symptoms and local demography.
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http://dx.doi.org/10.1136/sextrans-2016-052660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5969328PMC
May 2018

Population-Level Effects of Human Papillomavirus Vaccination Programs on Infections with Nonvaccine Genotypes.

Emerg Infect Dis 2016 10;22(10):1732-40

We analyzed human papillomavirus (HPV) prevalences during prevaccination and postvaccination periods to consider possible changes in nonvaccine HPV genotypes after introduction of vaccines that confer protection against 2 high-risk types, HPV16 and HPV18. Our meta-analysis included 9 studies with data for 13,886 girls and women ≤19 years of age and 23,340 women 20-24 years of age. We found evidence of cross-protection for HPV31 among the younger age group after vaccine introduction but little evidence for reductions of HPV33 and HPV45. For the group this same age group, we also found slight increases in 2 nonvaccine high-risk HPV types (HPV39 and HPV52) and in 2 possible high-risk types (HPV53 and HPV73). However, results between age groups and vaccines used were inconsistent, and the increases had possible alternative explanations; consequently, these data provided no clear evidence for type replacement. Continued monitoring of these HPV genotypes is important.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5038419PMC
http://dx.doi.org/10.3201/eid2210.160675DOI Listing
October 2016

Oral Human Papillomavirus Infection in Men Who Have Sex with Men: A Systematic Review and Meta-Analysis.

PLoS One 2016 6;11(7):e0157976. Epub 2016 Jul 6.

Research Department of Infection and Population Health, University College London, WC1E 6JB, London, United Kingdom.

Background: The epidemiology of oral human papillomavirus (HPV) infection in men who have sex with men (MSM) differs from anogenital HPV infection. The impact of HPV vaccination has, to date, largely focussed on anogenital outcomes. Vaccination of MSM in the UK has been recommended and, if implemented, baseline estimates of oral HPV prevalence will be useful.

Methods: We searched Medline, Embase and psycINFO databases for studies reporting prevalence, incidence, and clearance of oral HPV infection in MSM. We performed a random-effects meta-analysis and meta-regression on prevalence estimates and summarised within-study risk factors for oral HPV DNA detection and incidence/clearance rates. We also performed a meta-analysis of the effect of MSM on oral HPV prevalence compared to heterosexual men.

Results: 26 publications were identified. The pooled prevalence of oral HPV16 from twelve estimates was 3.0% (95%CI 0.5-5.5) in HIV-negative and 4.7% (95%CI 2.1-7.3) in HIV-positive MSM. Median age of study participants explained 38% of heterogeneity (p<0.01) in HPV prevalence estimates (pooled = 17% and 29% in HIV-negative and HIV-positive, respectively; 22 estimates). Nine studies compared MSM to heterosexual men and found no difference in oral HPV prevalence (pooled OR 1.07 (95%CI 0.65-1.74)). The clearance rate was higher than incidence within studies. Type-specific concordance between oral and anogenital sites was rare.

Conclusion: There was substantial heterogeneity between estimates of oral HPV prevalence in MSM populations that was partly explained by HIV status and median age.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0157976PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4934925PMC
July 2017

Continuing reductions in HPV 16/18 in a population with high coverage of bivalent HPV vaccination in England: an ongoing cross-sectional study.

BMJ Open 2016 Feb 11;6(2):e009915. Epub 2016 Feb 11.

HIV & STI Department, Centre for Infectious Disease Surveillance and Control, Public Health England, London, UK.

Objectives: The human papillomavirus (HPV) immunisation programme in England was introduced in 2008. Monitoring changes in type-specific HPV prevalence allows assessment of the population impact of this vaccination programme.

Methods: Residual vulva-vaginal swab specimens were collected from young sexually active women (aged 16-24 years) attending for chlamydia screening across England. Specimens were collected between 2010 and 2013 for type-specific HPV-DNA testing. HPV prevalence was compared to a similar survey conducted in 2008 prior to the introduction of HPV vaccination.

Results: A total of 7321 specimens collected in the postvaccination period, and 2354 specimens from the prevaccination period were included in this analysis. Among the individuals aged 16-18 years, with an estimated vaccination coverage of 67%, the prevalence of HPV16/18 infection decreased from 17.6% in 2008 to 6.1% in the postvaccination period. Within the postvaccination period, there was a trend towards lower HPV16/18 prevalence with higher vaccination coverage and increasing time since vaccine introduction from 8.5% in the period 2-3 years postvaccination to 4.0% in the period 4-5 years postvaccination. The prevalence of HPV31 reduced from 3.7% in the prevaccination period to 0.9% after vaccine introduction, although this no longer reached statistical significance after additional consideration of the uncertainty due to the assay change. Smaller reductions were seen in the individuals aged 19-21 years with lower estimated vaccination coverage, but there was no evidence of a reduction in the older unvaccinated women. Some overall increase in non-vaccine types was seen in the youngest age groups (ORs (95% CI); 1.3 (1.0 to 1.7) and 1.5 (1.1 to 2.0) for individuals aged 16-18 and 19-21 years, respectively, when adjusted for known population changes and the change in assay) although this should be interpreted with caution given the potential unmasking effect.

Conclusions: These data demonstrate a reduction in the HPV vaccine types in the age group with the highest HPV vaccination coverage.
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http://dx.doi.org/10.1136/bmjopen-2015-009915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762111PMC
February 2016

Naturally Occurring Major and Minor Capsid Protein Variants of Human Papillomavirus 45 (HPV45): Differential Recognition by Cross-Neutralizing Antibodies Generated by HPV Vaccines.

J Virol 2015 Dec 30;90(6):3247-52. Epub 2015 Dec 30.

Virus Reference Department, Public Health England, London, United Kingdom

We investigated naturally occurring variation within the major (L1) and minor (L2) capsid proteins of human papillomavirus genotype 45 (HPV45). Pseudoviruses (PsVs) representing HPV45 sublineages A1, A2, A3, B1, and B2 exhibited comparable particle-to-infectivity ratios and morphologies but demonstrated both increased (A2, A3, and B1) and decreased (B2) sensitivities to cross-neutralization by HPV vaccine antibodies compared to that of the A1 sublineage. Mutant PsVs identified HI loop residue 357 as being critical for conferring this differential sensitivity.
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http://dx.doi.org/10.1128/JVI.02859-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810639PMC
December 2015

Epidemiology of Mycoplasma genitalium in British men and women aged 16–44 years: evidence from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3).

Int J Epidemiol 2015 Dec;44(6):1982-94

Research Department of Infection and Population Health, University College London, London, UK.

Background: There are currently no large general population epidemiological studies of Mycoplasma genitalium (MG), which include prevalence, risk factors, symptoms and co-infection in men and women across a broad age range.

Methods: In 2010-–12, we conducted the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), a probability sample survey in Britain. Urine from 4507 sexually-experienced participants, aged 16–44 years, was tested for MG.

Results: MG prevalence was 1.2% [95% confidence interval (CI): 0.7–1.8%] in men and 1.3% (0.9–1.9%) in women. There were no positive MG tests in men aged 16–19, and prevalence peaked at 2.1% (1.2–3.7%) in men aged 25–34 years. In women, prevalence was highest in 16–19 year olds, at 2.4% (1.2–4.8%), and decreased with age. Men of Black ethnicity were more likely to test positive for MG [adjusted odds ratio (AOR) 12.1; 95% CI: 3.7–39.4). For both men and women, MG was strongly associated with reporting sexual risk behaviours (increasing number of total and new partners, and unsafe sex, in the past year). Women with MG were more likely to report post-coital bleeding (AOR 5.8; 95%CI 1.4–23.3). However, the majority of men (94.4%), and over half of women (56.2%) with MG did not report any sexually transmitted infection (STI) symptoms. Men with MG were more likely to report previously diagnosed gonorrhoea, syphilis or non-specific urethritis, and women previous trichomoniasis.

Conclusions: This study strengthens evidence that MG is an STI. MG was identified in over 1% of the population, including in men with high-risk behaviours in older age groups that are often not included in STI prevention measures.
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http://dx.doi.org/10.1093/ije/dyv194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690003PMC
December 2015

Relationship between Humoral Immune Responses against HPV16, HPV18, HPV31 and HPV45 in 12-15 Year Old Girls Receiving Cervarix® or Gardasil® Vaccine.

PLoS One 2015 23;10(10):e0140926. Epub 2015 Oct 23.

Virus Reference Department, Public Health England, London, United Kingdom.

Background: Human papillomavirus (HPV) vaccines confer protection against the oncogenic genotypes HPV16 and HPV18 through the generation of type-specific neutralizing antibodies raised against virus-like particles (VLP) representing these genotypes. The vaccines also confer a degree of cross-protection against HPV31 and HPV45, which are genetically-related to the vaccine types HPV16 and HPV18, respectively, although the mechanism is less certain. There are a number of humoral immune measures that have been examined in relation to the HPV vaccines, including VLP binding, pseudovirus neutralization and the enumeration of memory B cells. While the specificity of responses generated against the vaccine genotypes are fairly well studied, the relationship between these measures in relation to non-vaccine genotypes is less certain.

Methods: We carried out a comparative study of these immune measures against vaccine and non-vaccine genotypes using samples collected from 12-15 year old girls following immunization with three doses of either Cervarix® or Gardasil® HPV vaccine.

Results: The relationship between neutralizing and binding antibody titers and HPV-specific memory B cell levels for the vaccine genotypes, HPV16 and HPV18, were very good. The proportion of responders approached 100% for both vaccines while the magnitude of these responses induced by Cervarix® were generally higher than those following Gardasil® immunization. A similar pattern was found for the non-vaccine genotype HPV31, albeit at a lower magnitude compared to its genetically-related vaccine genotype, HPV16. However, both the enumeration of memory B cells and VLP binding responses against HPV45 were poorly related to its neutralizing antibody responses. Purified IgG derived from memory B cells demonstrated specificities similar to those found in the serum, including the capacity to neutralize HPV pseudoviruses.

Conclusions: These data suggest that pseudovirus neutralization should be used as the preferred humoral immune measure for studying HPV vaccine responses, particularly for non-vaccine genotypes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0140926PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4619723PMC
June 2016

Male Circumcision and STI Acquisition in Britain: Evidence from a National Probability Sample Survey.

PLoS One 2015 17;10(6):e0130396. Epub 2015 Jun 17.

Research Department of Infection and Population Health, University College London, London, United Kingdom.

Background: It is well-established that male circumcision reduces acquisition of HIV, herpes simplex virus 2, chancroid, and syphilis. However, the effect on the acquisition of non-ulcerative sexually transmitted infections (STIs) remains unclear. We examined the relationship between circumcision and biological measures of three STIs: human papillomavirus (HPV), Chlamydia trachomatis and Mycoplasma genitalium.

Methods: A probability sample survey of 15,162 men and women aged 16-74 years (including 4,060 men aged 16-44 years) was carried out in Britain between 2010 and 2012. Participants completed a computer-assisted personal interview, including a computer-assisted self-interview, which asked about experience of STI diagnoses, and circumcision. Additionally, 1,850 urine samples from sexually-experienced men aged 16-44 years were collected and tested for STIs. Multivariable logistic regression was used to calculate adjusted odds ratios (AOR) to quantify associations between circumcision and i) self-reporting any STI diagnosis and ii) presence of STIs in urine, in men aged 16-44 years, adjusting for key socio-demographic and sexual behavioural factors.

Results: The prevalence of circumcision in sexually-experienced men aged 16-44 years was 17.4% (95%CI 16.0-19.0). There was no association between circumcision and reporting any previous STI diagnoses, and specifically previous chlamydia or genital warts. However, circumcised men were less likely to have any HPV type (AOR 0.26, 95% confidence interval (CI) 0.13-0.50) including high-risk HPV types (HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and/or 68) (AOR 0.14, 95% CI 0.05-0.40) detected in urine.

Conclusions: Circumcised men had reduced odds of HPV detection in urine. These findings have implications for improving the precision of models of STI transmission in populations with different circumcision prevalence and in designing interventions to reduce STI acquisition.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0130396PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471189PMC
May 2016

Naturally Occurring Capsid Protein Variants of Human Papillomavirus Genotype 31 Represent a Single L1 Serotype.

J Virol 2015 Aug 20;89(15):7748-57. Epub 2015 May 20.

Virus Reference Department, Public Health England, London, United Kingdom

Unlabelled: We investigated naturally occurring variation within the major (L1) and minor (L2) capsid proteins of oncogenic human papillomavirus (HPV) genotype 31 (HPV31) to determine the impact on capsid antigenicity. L1L2 pseudoviruses (PsVs) representing the three HPV31 variant lineages, variant lineages A, B, and C, exhibited comparable particle-to-infectivity ratios and morphologies. Lineage-specific L1L2 PsVs demonstrated subtle differences in susceptibility to neutralization by antibodies elicited following vaccination or preclinical L1 virus-like particle (VLP) immunization or by monoclonal antibodies; however, these differences were generally of a low magnitude. These data indicate that the diagnostic lineage-specific single nucleotide polymorphisms within the HPV31 capsid genes have a limited effect on L1 antibody-mediated neutralization and that the three HPV31 variant lineages belong to a single L1 serotype. These data contribute to our understanding of HPV L1 variant antigenicity.

Importance: The virus coat (capsid) of the human papillomavirus contains major (L1) and minor (L2) capsid proteins. These proteins facilitate host cell attachment and viral infectivity and are the targets for antibodies which interfere with these events. In this study, we investigated the impact of naturally occurring variation within these proteins upon susceptibility to viral neutralization by antibodies induced by L1 VLP immunization. We demonstrate that HPV31 L1 and L2 variants exhibit similar susceptibility to antibody-mediated neutralization and that for the purposes of L1 VLP-based vaccines, these variant lineages represent a single serotype.
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http://dx.doi.org/10.1128/JVI.00842-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505685PMC
August 2015

Oral human papillomavirus (HPV) infection in men who have sex with men: prevalence and lack of anogenital concordance.

Sex Transm Infect 2015 Jun 17;91(4):284-6. Epub 2015 Apr 17.

Research Department of Infection and Population Health, University College London, London, UK.

Objectives: To estimate the prevalence of oral detectable human papillomavirus (HPV) DNA in HIV-negative men who have sex with men (MSM) attending a sexual health clinic in London and concordance with anogenital HPV infection. Such data are important to improve our understanding of the epidemiology of oral HPV and the potential use of vaccines to prevent oropharyngeal cancers.

Methods: Paired oral rinse samples and anogenital samples were available from 151 HIV-negative MSM within a larger cross-sectional survey. All samples were tested in parallel for 21 types of HPV DNA using an in-house assay.

Results: The median age of participants was 30 (IQR 25-35). The prevalence of any oral HPV and of high-risk HPV (HR-HPV) was 13.7% (n=21; 95% CI 8.7 to 20.2) and 5.9% (n=9; 95% CI 2.7 to 10.9) compared with 64.9% (n=98; 95% CI 56.7 to 72.5) and 34.4% (n=52; 95% CI 26.9 to 42.6) in any anogenital sample, respectively. The prevalence of types prevented by the bivalent (HPV16/18), quadrivalent (HPV6/11/16/18) and nonavalent (HPV6/11/16/18/31/33/45/52/58) vaccines was 1.3% (95% CI 0.2 to 4.7), 2.6% (95% CI 0.7 to 6.6) and 4.6% (95% CI 1.9 to 9.3), respectively. There was no concordance between HPV genotypes detected in oral and anogenital sites.

Conclusions: HR-HPV DNA, including HPV 16/18, was detected in oral specimens from HIV-negative MSM attending sexual health clinics, suggesting a potential role for vaccination, but is far less common than anogenital infection. How this relates to the risk and natural history of HPV-related head and neck cancers warrants further study. Lack of concordance with anogenital infection also suggests that oral HPV infection should be considered separately when estimating potential vaccine impact.
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http://dx.doi.org/10.1136/sextrans-2014-051955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453633PMC
June 2015

Amino acid motifs in both the major and minor capsid proteins of HPV51 impact antigenicity and infectivity.

J Gen Virol 2015 Jul 13;96(Pt 7):1842-9. Epub 2015 Mar 13.

1Virus Reference Department, Public Health England, London, UK.

Persistent infection with oncogenic human papillomavirus (HPV) is a prerequisite for cervical disease development, yet data regarding the host immune response to infection at the genotype level are quite limited. We created pseudoviruses bearing the major (L1) and minor (L2) capsid proteins and L1 virus-like particles representing the reference sequence and a consensus of 34 European sequences of HPV51. Despite the formation of similarly sized particles, motifs in the reference L1 and L2 genes had a profound impact on the immunogenicity, antigenicity and infectivity of these antigens. The antibody status of women exhibiting low-grade disease was similar between HPV16 and the consensus HPV51, but both demonstrated discrepancies between binding and neutralizing antibody responses. These data support the use of pseudoviruses as the preferred target antigen in studies of natural HPV infection and the need to consider variation in both the L1 and L2 proteins for the appropriate presentation of antibody epitopes.
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http://dx.doi.org/10.1099/vir.0.000121DOI Listing
July 2015
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