Publications by authors named "David Mesher"

36 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

Reproducibility of a Rapid Human Papillomavirus Test at Different Levels of the Healthcare System in Tanzania: The AISHA Study.

Cancer Epidemiol Biomarkers Prev 2020 11 20;29(11):2261-2268. Epub 2020 Aug 20.

Department of Reproductive Health and Research, World Health Organization, Geneva, Switzerland.

Background: To inform policy makers in Tanzania if and how best to implement rapid HPV testing, we assessed the interobserver reproducibility of HPV test at three different levels of the healthcare system in an urban and a rural region of Tanzania.

Methods: Women aged 30 to 50 years were screened by HPV testing in two primary healthcare centers (PHC), two district hospitals (DiH), and two regional hospitals (ReH). Aliquots were retested at regional (ReH) and national referral laboratories (NRL). Reproducibility was evaluated using agreement and kappa index measures. Intralaboratory reproducibility was also evaluated in a set of 10 positive and 10 negative samples.

Results: Samples from 1,134 women were locally tested and retested at ReH and/or NRL. Test results from Dar es Salaam ReH and Kilimanjaro PHC showed clear quality problems including suspicion of contamination during testing or aliquoting. After excluding these samples, 18.8% of 743 women were HPV positive at clinic level. The resulting HPV reproducibility at different levels of the healthcare system was very good [agreement 95.7%, 95% confidence interval (CI), 94.0-96.9; kappa, 0.86, 95% CI, 0.81-0.91]. Intralaboratory agreement was also very good across four different experiments, with Fleiss' kappa between 0.87 (95% CI, 0.61-1.00) and 1.00 (0.75-1.00).

Conclusions: Rapid HPV testing was highly reproducible between lower and higher levels of the healthcare system in Tanzania; however, performance seems to be operator dependent.

Impact: The HPV test seems to be a feasible option for cervical cancer screening in an organized, decentralized system and in limited-resource settings if quality assurance measures are in place.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0422DOI Listing
November 2020

Response to Berlaimont and Welby.

Sex Transm Infect 2019 11 18;95(7):553. Epub 2019 Jul 18.

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

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http://dx.doi.org/10.1136/sextrans-2019-054148DOI Listing
November 2019

HPV vaccination of gay, bisexual and other men who have sex with men in sexual health and HIV clinics in England: vaccination uptake and attendances during the pilot phase.

Sex Transm Infect 2019 12 26;95(8):608-613. Epub 2019 Apr 26.

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

Background: Human papillomavirus (HPV) vaccination for gay, bisexual and other men who have sex with men (GBMSM) aged up to 45 years attending sexual health clinics (SHC) and HIV clinics began in England as a pilot in June 2016, with national roll-out from April 2018. The recommended course is three doses of the quadrivalent HPV vaccine over one to 2 years. We present the methodology and results of monitoring vaccination uptake (initiation and completion), and attendance patterns, during the pilot phase.

Methods: Total numbers of eligible GBMSM receiving HPV vaccine doses were extracted from routine datasets from pilot start to end of March 2018. Numbers of attendances since January 2009 were extracted and tested for trends before and after introduction of HPV vaccination.

Results: Overall, first dose uptake was 49.1 % (23 619/48 095), with clinics with highest data completeness achieving close to 90% uptake during the pilot period. Refusals were very low (3.5%). There was no evidence of increases in the number of GBMSM attendances at pilot SHC.

Conclusions: HPV vaccination has not caused important deviations to expected attendance patterns of GBMSM at SHC throughout the pilot phase. Overall, recorded initiation has been encouraging given known issues with data recording, as is current status of second and third dose completion. Attendances, vaccination initiation and completion will continue to be monitored alongside surveillance of anogenital warts diagnoses and of rectal HPV prevalence.
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http://dx.doi.org/10.1136/sextrans-2018-053923DOI Listing
December 2019

Implementation and evaluation of the human papillomavirus (HPV) vaccination pilot for men who have sex with men (MSM), England, April 2016 to March 2017.

Euro Surveill 2019 Feb;24(8)

Immunisation and countermeasures division, National Infection Service, Public Health England, London, United Kingdom.

Background: Opportunistic human papillomavirus (HPV) vaccination for men who have sex with men (MSM) was piloted in sexual health clinics (SHC) in England between 2016 and 2018.

Aim: to evaluate the pilot's first year (April 2016-March 2017) in terms of feasibility, acceptability, uptake, impact and equity and interpret the outcome in the context of wide HPV vaccination policy.

Methods: Attendance and uptake data from routine SHC surveillance datasets and a cross-sectional survey administered to individuals receiving the vaccine were analysed.

Results: Among 18,875 eligible MSM, 8,580 (45.5%) were recorded as having received one HPV vaccine dose, decreasing slightly with increasing age, and uptake was higher in rural than urban areas. Survey results suggested that of those receiving the first dose of HPV vaccine, 8% were new attendees and that among those, less than 11% attended just to receive the vaccine. Of those having their first HPV vaccination, 95% indicated they would like to receive the next vaccine doses at the same clinic and 85% of patients reported accessing other services when visiting SHC for the first dose of vaccine.

Conclusion: An opportunistic HPV vaccination programme for MSM can be delivered in an acceptable and, as far as can be evaluated, equitable manner, without major disruption to SHC and HIV clinics.
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http://dx.doi.org/10.2807/1560-7917.ES.2019.24.8.1800055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446955PMC
February 2019

Declines in anogenital warts diagnoses since the change in 2012 to use the quadrivalent HPV vaccine in England: data to end 2017.

Sex Transm Infect 2019 08 5;95(5):368-373. Epub 2019 Feb 5.

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

Objectives: In 2008, a national human papillomavirus (HPV) vaccination programme for females was introduced in England using the bivalent vaccine (HPV16 and 18 only). In 2012, the programme changed to offer the quadrivalent vaccine that includes protection against the two HPV types that cause the majority of anogenital warts (AGW; HPV6 and 11). We present data reporting AGW diagnoses in sexual health clinics (SHCs) in England to the end of 2017, including diagnoses among birth cohorts offered the quadrivalent vaccine.

Methods: Using data from all SHCs across England, we performed ecological analyses to consider rates of AGW diagnoses by age, gender and sexual orientation. We tested for trends over time of diagnoses of AGW in young females, heterosexual males, and men who have sex with men (MSM) between the ages of 15 and 24 years during both bivalent (2009 to 2013) and quadrivalent (2014 to 2017) vaccine time periods using Poisson regression.

Results: Between 2014 and 2017, there was strong evidence for a decreasing trend in the rate of AGW diagnoses at SHC among females aged 15-17 years from 257.5 to 45.7 per 100 000 population (82.3% decline) and same aged heterosexual males from 59.1 to 19.1 per 100 000 population (67.7% decline). The reductions in the incidence of AGW diagnoses in MSM aged 15-17 years were less clear (decreased by 13.6% between 2014 and 2017, from 129.9 to 112.2 per 100 000 population).

Conclusions: The moderate, unexpected declines in AGW seen since the introduction of a high-coverage HPV vaccination programme using the bivalent vaccine are being followed, as expected, by much larger declines among females offered the quadrivalent vaccine and same-aged heterosexual males. Surveillance plans are in place to continue to monitor AGW diagnoses to evaluate the impact of both female and targeted MSM HPV vaccination on early disease outcomes.
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http://dx.doi.org/10.1136/sextrans-2018-053751DOI Listing
August 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

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

Understanding differences in cervical cancer incidence in Western Europe: comparing Portugal and England.

Eur J Public Health 2018 04;28(2):343-347

Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.

Background: Cervical cancer incidence has decreased over time in England particularly after the introduction of organized screening. In Portugal, where opportunistic screening has been widely available with only slightly lower coverage than that of the organized programme in England, rates of cervical cancer have been higher than in England. We compared the burden of cervical cancer, risk factors and preventive interventions over time in both countries, to identify elements hindering the further decline in incidence and mortality in Portugal.

Methods: We used joinpoint regression to identify significant changes in rate time-trends. We also analyzed individual-level Portuguese data on sexual behaviour and human papillomavirus prevalence, and recent aggregate data on organized and opportunistic screening coverage. We compared published estimates of survival, risk factors and historical screening coverage for both countries.

Results: Despite stable incidence, cervical cancer mortality has declined in both countries in the last decade. The burden has been 4 cases and 1 death per 100 000 women annually higher in Portugal than in England. Differences in human papillomavirus prevalence and risk factors for infection and disease progression do not explain the difference found in cervical cancer incidence. Significant mortality declines in both countries followed the introduction of different screening policies, although England showed a greater decline than Portugal over nearly 2 decades after centralizing organized screening.

Conclusion: The higher rates of cervical cancer in Portugal compared to England can be explained by differences in screening quality and coverage.
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http://dx.doi.org/10.1093/eurpub/ckx176DOI Listing
April 2018

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

Attendance of MSM at Genitourinary Medicine services in England: implications for selective HPV vaccination programme (a short communication).

Sex Transm Infect 2018 11 9;94(7):542-544. Epub 2017 Mar 9.

Public Health England, London, UK.

Background: Human papillomaviruses (HPV) immunisation programmes for female adolescents in the UK offer relatively little benefit to men who have sex with men (MSM). Targeted HPV vaccination for MSM may reduce the high incidence of HPV-related disease among MSM. We used national data from sexual health clinics to calculate the number of MSM attending these clinics throughout England from 2009 to 2014 and to identify their characteristics, to inform the implementation of a targeted HPV vaccination programme in MSM.

Methods: We used the Genitourinary Medicine Clinic Activity Dataset (GUMCADv2) to obtain data for men aged 15-70 years who had attended a GUM clinic in England from 2009 to 2014. We analysed both numbers of MSM attending and number of GUM attendances, age at first attendance, ethnicity and geographical area of the clinic in England.

Results: A total of 374 983 MSM attended sexual health services in England between 2009 and 2014. Median age of presentation was 32 years (IQR 25-41) and showed regional geographical variation. Of all men attending sexual health clinics in England, the highest proportion of those identifying as MSM was in London (21%). Excluding visits within 1 month of an initial attendance, 49% of all MSM re-attended within 12 months and 58% within 24 months. MSM aged ≥36 years reattended more frequently than younger MSM. 51% reattended at least twice within 24 months of initial visit.

Conclusions: The majority of MSM reattend clinic at least once within a 24-month period, potentially facilitating the delivery of a three-dose HPV vaccination programme. This would reduce the burden on sexual health clinics and cost to local authorities due to extra visits if HPV vaccination were to be delivered through these services.
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http://dx.doi.org/10.1136/sextrans-2016-052912DOI Listing
November 2018

Impact and Cost-effectiveness of Selective Human Papillomavirus Vaccination of Men Who Have Sex With Men.

Clin Infect Dis 2017 03;64(5):580-588

Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.

Background: Men who have sex with men (MSM) have a high lifetime risk of anogenital warts and cancers related to infection with human papillomavirus (HPV). They also benefit less from herd protection than heterosexual males in settings with female-only HPV vaccination.

Methods: We evaluated the potential health impact and cost-effectiveness of offering vaccination to MSM who visit genitourinary medicine (GUM) clinics. We used a mathematical model of HPV 6/11/16/18 sexual transmission within an MSM population in England, parameterized with sexual behaviour, GUM attendance, HPV prevalence, HIV prevalence, warts, and cancer incidence data. Interventions considered were offering HPV vaccination to either HIV-positive MSM or MSM regardless of HIV status, for age bands 16-25, 16-30, 16-35, and 16-40 years.

Results: Substantial declines in anogenital warts and male HPV-related cancer incidence are projected to occur following an offer of vaccination to MSM. MSM not attending GUM clinics will partially benefit from herd protection. Offering vaccination to HIV-positive MSM up to age 40 is likely to be cost-effective if vaccine procurement and administration costs are below £96.50 a dose. At £48 a dose, offering vaccination to all MSM up to age 40 is likely to be cost-effective.

Conclusions: Quadrivalent HPV vaccination of MSM via GUM clinics is likely to be an effective and cost-effective way of reducing the burden of HPV-related disease in MSM.
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http://dx.doi.org/10.1093/cid/ciw845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5404831PMC
March 2017

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

HPV Serology Testing Confirms High HPV Immunisation Coverage in England.

PLoS One 2016 9;11(3):e0150107. Epub 2016 Mar 9.

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

Background: Reported human papillomavirus (HPV) vaccination coverage in England is high, particularly in girls offered routine immunisation at age 12 years. Serological surveillance can be used to validate reported coverage and explore variations within it and changes in serological markers over time.

Methods: Residual serum specimens collected from females aged 15-19 years in 2010-2011 were tested for anti-HPV16 and HPV18 IgG by ELISA. Based on these results, females were classified as follows: seronegative, probable natural infection, probable vaccine-induced seropositivity, or possible natural infection/possible vaccine-induced seropositivity. The proportion of females with vaccine-induced seropositivity was compared to the reported vaccination coverage.

Results: Of 2146 specimens tested, 1380 (64%) were seropositive for both types HPV16 and HPV18 and 159 (7.4%) positive for only one HPV type. The IgG concentrations were far higher for those positive for both HPV types than those positive for only one HPV type. 1320 (62%) females were considered to have probable vaccine-induced seropositivity. Among vaccine-induced seropositives, antibody concentrations declined with increasing age at vaccination and increasing time since vaccination.

Conclusions: The proportion of females with vaccine-induced seropositivity was closest to the reported 3-dose coverage in those offered the vaccination at younger ages, with a greater discrepancy in the older females. This suggests either some under-reporting of immunisations of older females and/or that partial vaccination (i.e. one- or two-doses) has provided high antibody responses in 13-17 year olds.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0150107PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4784902PMC
August 2016

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

Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis.

Lancet Infect Dis 2015 May 3;15(5):565-80. Epub 2015 Mar 3.

Centre de Recherche du CHU de Québec, Québec, QC, Canada; Département de Médecine Sociale et Préventive, Université Laval, Québec, QC, Canada; Department of Infectious Disease Epidemiology, Imperial College London, London, UK. Electronic address:

Background: Human papillomavirus (HPV) vaccination programmes were first implemented in several countries worldwide in 2007. We did a systematic review and meta-analysis to assess the population-level consequences and herd effects after female HPV vaccination programmes, to verify whether or not the high efficacy reported in randomised controlled clinical trials are materialising in real-world situations.

Methods: We searched the Medline and Embase databases (between Jan 1, 2007 and Feb 28, 2014) and conference abstracts for time-trend studies that analysed changes, between the pre-vaccination and post-vaccination periods, in the incidence or prevalence of at least one HPV-related endpoint: HPV infection, anogenital warts, and high-grade cervical lesions. We used random-effects models to derive pooled relative risk (RR) estimates. We stratified all analyses by age and sex. We did subgroup analyses by comparing studies according to vaccine type, vaccination coverage, and years since implementation of the vaccination programme. We assessed heterogeneity across studies using I(2) and χ(2) statistics and we did trends analysis to examine the dose-response association between HPV vaccination coverage and each study effect measure.

Findings: We identified 20 eligible studies, which were all undertaken in nine high-income countries and represent more than 140 million person-years of follow-up. In countries with female vaccination coverage of at least 50%, HPV type 16 and 18 infections decreased significantly between the pre-vaccination and post-vaccination periods by 68% (RR 0·32, 95% CI 0·19-0·52) and anogenital warts decreased significantly by 61% (0·39, 0·22-0·71) in girls 13-19 years of age. Significant reductions were also recorded in HPV types 31, 33, and 45 in this age group of girls (RR 0·72, 95% CI 0·54-0·96), which suggests cross-protection. Additionally, significant reductions in anogenital warts were also reported in boys younger than 20 years of age (0·66 [95% CI 0·47-0·91]) and in women 20-39 years of age (0·68 [95% CI 0·51-0·89]), which suggests herd effects. In countries with female vaccination coverage lower than 50%, significant reductions in HPV types 16 and 18 infection (RR 0·50, 95% CI 0·34-0·74]) and in anogenital warts (0·86 [95% CI 0·79-0·94]) occurred in girls younger than 20 years of age, with no indication of cross-protection or herd effects.

Interpretation: Our results are promising for the long-term population-level effects of HPV vaccination programmes. However, continued monitoring is essential to identify any signals of potential waning efficacy or type-replacement.

Funding: The Canadian Institutes of Health Research.
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http://dx.doi.org/10.1016/S1473-3099(14)71073-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5144106PMC
May 2015

Estimating the workload associated with symptoms-based ovarian cancer screening in primary care: an audit of electronic medical records.

BMC Fam Pract 2014 Dec 12;15:200. Epub 2014 Dec 12.

Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.

Background: Ovarian cancer is the most lethal gynaecological malignancy in the United Kingdom (UK). Studies have found that many women with ovarian cancer have symptoms for several months before diagnosis. Using a symptoms-based tool to diagnose ovarian cancer (OC) earlier is appealing, but may increase general practitioner (GP) workload because the symptoms are typically vague and non-specific. This study aimed to provide estimates of the GP workload associated with offering symptoms-based ovarian cancer screening.

Methods: A cross-sectional analysis of electronic records from four general practices in England, UK. We downloaded anonymous data on women aged 45-74 who consulted over one week to estimate the proportion who would be offered 'screening' according to the UK National Institute for Health and Care Excellence (NICE) guidelines and a symptoms index (Index 2) over one year. We used previous consultations (censoring women with no prior symptom at the date of their last recorded consultation) to estimate the proportion of women presenting with a new (not recorded in previous 12 months) NICE symptom each year.

Results: Data were obtained from 19,558 women. The proportion presenting over one week varied between practices (5%-14%), however, the proportion with an OC symptom was similar (17% overall). Over one year, an estimated 51.8% (95% CI 44.0%-59.7%) would present with an OC symptom, 26.6% (95% CI 19.3%-35.1%) with a NICE symptom and 20.3% (95% CI 13.7%-28.5%) with an Index 2 symptom. Each year, an estimated 11.9% (95% CI 5.0%-18.3%) of women would present with a new NICE symptom.

Conclusion: One in two women aged 45-74 present to primary care at least once a year with an OC symptom, 11.9% with a new NICE symptom. This would be comparable to 2 to 8 yearly screening (depending on what symptoms triggered testing).
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http://dx.doi.org/10.1186/s12875-014-0200-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271462PMC
December 2014

Type-specific HPV prevalence in invasive cervical cancer in the UK prior to national HPV immunisation programme: baseline for monitoring the effects of immunisation.

J Clin Pathol 2015 Feb 19;68(2):135-40. Epub 2014 Nov 19.

Centre for Infectious Disease Surveillance and Control, Public Health England, London, UK.

Aims: To establish the human papillomavirus (HPV) type-specific prevalence in cervical cancer and high-grade cervical lesions in the UK prior to the introduction of national HPV vaccination.

Methods: Specimens of cervical cancer (n=1235) and cervical intraepithelial neoplasia (CIN)3 (n=2268) were tested for HPV genotypes in England, Scotland, Wales and Northern Ireland. Data were pooled and weighted estimates presented.

Results: Among cervical cancer cases, 95.8% were positive for at least one high-risk (HR) HPV type. Restricting to those with HR HPV, the proportion positive for HPV16 and/or HPV18 was similar across countries (weighted overall prevalence 83.0%). This proportion decreased with increasing age at diagnosis (p=0.0005). HPV31, HPV33, HPV45, HPV52 and/or HPV58 were detected in 16.1% of HR HPV-positive cervical cancers and there was no significant association with age for these types. For HR HPV-positive CIN3 cases, there was a similar age-specific pattern with the highest positivity of HPV16 and/or HPV18 in the youngest age group (77.2%). The proportion of HR HPV CIN3 cases positive for HPV31, HPV33, HPV45, HPV52 and/or HPV58 was 36.3% in those aged <30 years at diagnosis.

Conclusions: The prevalence of HPV 16 and/or 18 was high in all UK countries and highest in those diagnosed at a younger age. The UK is well placed to monitor the impact of HPV vaccination on type-specific HPV prevalence in cervical disease.
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http://dx.doi.org/10.1136/jclinpath-2014-202681DOI Listing
February 2015

Declining genital Warts in young women in england associated with HPV 16/18 vaccination: an ecological study.

J Infect Dis 2013 Nov;208(9):1397-403

HIV/STI Department, Public Health England.

Background: Diagnoses of genital warts (GW) in genitourinary medicine (GUM) clinics have been increasing in England for many years. In 2008, an HPV immunization program began with a bivalent vaccine (Cervarix). This was expected to markedly reduce infections and disease due to human papillomavirus (HPV) 16/18 but not HPV 6/11 infections or disease. However, from 2009 to 2011 there were decreases in reported diagnoses of GW in young females at GUM clinics.

Methods: Using data from GUM clinics and a sample of general practices (GPs) throughout England, we analyzed rates of GW diagnoses by age, year of diagnosis, and estimated immunization coverage.

Results: The overall reduction in GW diagnoses at GUM clinics between 2008 and 2011 was 13.3% among 16- to 19-year-old females, with the greatest decline of 20.8% in 17-year-olds. Declines were positively associated with estimated immunization coverage. A similar pattern was seen in GP diagnoses, but not among older women, and for other GUM consultations.

Conclusions: Several factors might contribute to declines in GW. However, the size and pattern of the declines strongly suggest that we are observing an unexpected, moderately protective effect of HPV 16/18 vaccination against GW.
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http://dx.doi.org/10.1093/infdis/jit361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3789575PMC
November 2013

A pooled analysis of the outcome of prospective colonoscopic surveillance for familial colorectal cancer.

Int J Cancer 2014 Feb 29;134(4):939-47. Epub 2013 Aug 29.

Queen Mary University of London, Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Charterhouse Square, London, United Kingdom.

Surveillance guidelines for the management of familial colorectal cancer (FCC), a dominant family history of colorectal cancer in which the polyposis syndromes and Lynch syndrome have been excluded, are not firmly established. The outcome of colonoscopic surveillance is studied using data from six centers. DNA mismatch repair deficiency was excluded by genetic testing. Families were classified as FCC type X if they fulfilled the original Amsterdam criteria (AC) and late onset (LOFCC) if they fulfilled the AC apart from not having a cancer aged under 50. The most advanced findings on colonoscopy were analyzed. One thousand five hundred eighty-five individuals (median age 47.3, 44% male) from 530 FCC families (349 FCC type X) underwent a total of 4,992 colonoscopies with 7,904 patient-years of follow-up. Results for FCC type X and LOFCC were very similar. At baseline, 22 prevalent asymptomatic colorectal cancers were diagnosed, 120 (7.6%) individuals had high-risk adenomas and 225 (14.2%) simple adenomas. One thousand eighty-eight individuals had a further colonoscopy (median follow-up of 6.2 years). Of nine individuals diagnosed with cancer, eight had a previous history of at least one polyp/adenoma. High-risk adenomas were detected in 92 (8.7%) and multiple adenomas were detected in 20 (1.9%) individuals. Both FCC type X and LOFCC have a high prevalence of colorectal cancers and on follow-up develop high-risk adenomas (including multiple adenomas), but infrequent interval cancers. They should be managed similarly with five-yearly colonoscopies undertaken from between 30 and 40 with more intensive surveillance in individuals developing multiple or high-risk adenomas.
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http://dx.doi.org/10.1002/ijc.28397DOI Listing
February 2014

Comparison of human papillomavirus testing strategies for triage of women referred with low-grade cytological abnormalities.

Eur J Cancer 2013 Jun 26;49(9):2179-86. Epub 2013 Feb 26.

Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary, University of London, Charterhouse Square, London EC1M 6BQ, UK. Electronic address:

Aim: To compare triage strategies using different human papillomavirus (HPV) consensus and genotyping tests and a p16(INK4a) test.

Methods: 1228 women referred with a borderline or single mildly dyskaryotic smear. Samples were taken at colposcopy using PreservCyt. Tests included Hybrid Capture 2, Abbott RealTime PCR, BD HPV, Cobas 4800, PreTect HPV-Proofer, APTIMA and p16(INK4a). Results were based on the worst histology within 9 months.

Results: 97/1228 (7.9%) women had CIN3+ (203/1228 (17%) CIN2+). HPV testing alone using Hybrid Capture 2, Abbott RealTime PCR, BD HPV, Cobas 4800 or APTIMA had a sensitivity for CIN3+ ranging from 99.0% to 100.0% and specificity for
Conclusions: Triage with sensitive HPV testing assays can substantially reduce the number of unnecessary referrals in women with low grade cytology with virtually no loss of sensitivity. Even greater gains can be made if p16 and type 16 are used, but some cases of CIN2 will be missed. In both cases short term surveillance will be needed.
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http://dx.doi.org/10.1016/j.ejca.2013.01.018DOI Listing
June 2013

p63 is an alternative p53 repressor in melanoma that confers chemoresistance and a poor prognosis.

J Exp Med 2013 Mar 18;210(3):581-603. Epub 2013 Feb 18.

Centre for Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, England, UK.

The role of apoptosis in melanoma pathogenesis and chemoresistance is poorly characterized. Mutations in TP53 occur infrequently, yet the TP53 apoptotic pathway is often abrogated. This may result from alterations in TP53 family members, including the TP53 homologue TP63. Here we demonstrate that TP63 has an antiapoptotic role in melanoma and is responsible for mediating chemoresistance. Although p63 was not expressed in primary melanocytes, up-regulation of p63 mRNA and protein was observed in melanoma cell lines and clinical samples, providing the first evidence of significant p63 expression in this lineage. Upon genotoxic stress, endogenous p63 isoforms were stabilized in both nuclear and mitochondrial subcellular compartments. Our data provide evidence of a physiological interaction between p63 with p53 whereby translocation of p63 to the mitochondria occurred through a codependent process with p53, whereas accumulation of p53 in the nucleus was prevented by p63. Using RNA interference technology, both isoforms of p63 (TA and ΔNp63) were demonstrated to confer chemoresistance, revealing a novel oncogenic role for p63 in melanoma cells. Furthermore, expression of p63 in both primary and metastatic melanoma clinical samples significantly correlated with melanoma-specific deaths in these patients. Ultimately, these observations provide a possible explanation for abrogation of the p53-mediated apoptotic pathway in melanoma, implicating novel approaches aimed at sensitizing melanoma to therapeutic agents.
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http://dx.doi.org/10.1084/jem.20121439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3600906PMC
March 2013

The prognostic value of Ki-67 expression in penile squamous cell carcinoma.

J Clin Pathol 2012 Jun 23;65(6):534-7. Epub 2012 Mar 23.

Department of Molecular Oncology, Barts Cancer Institute, London, UK.

Aims: To determine whether Ki-67 immunoexpression in penile squamous cell carcinoma (PSCC) has a prognostic value and correlates with lymph node metastasis, human papillomavirus (HPV) infection and patient survival.

Methods: 148 formalin-fixed paraffin-embedded PSCC samples were tissue-microarrayed, including 97 usual-type SCCs, 17 basaloid, 15 pure verrucous carcinomas, 2 warty and 17 mixed-type tumours. All samples were immunostained for Ki-67 protein. HPV DNA was detected with INNO-LiPA assay. Follow-up data were available for 134 patients.

Results: Ki-67 was strongly expressed in 57/148 (38.5%) of PSCCs. Different cancer subtypes showed significant difference in Ki-67 expression (p<0.0001) with highest positivity in basaloid, 16/17 (94%), followed by usual type, 38/97 (39%) and lack of Ki-67 positive cases within verrucous tumours, 0/15. Ki-67 positively correlated with high-risk HPV (p<0.0001) and showed good specificity (84%) but low sensitivity (61%) for high-risk HPV detection. Ki-67 protein strongly positively correlated with tumour grade (p<0.0001) but not with stage (p=0.2193), or lymph node status (p=0.7366). Ki-67 showed no prognostic value for cancer-specific survival (HR=1.00, 95%, CI 0.99 to 1.02, p=0.54) or overall survival (HR=1.00, 95%, CI 0.99 to 1.02, p=0.45). High tumour stage, lymph node metastasis, high tumour grade and age at diagnosis were all independent prognostic factors for cancer-specific survival and overall survival.

Conclusions: Ki-67 is only a moderate surrogate marker for HPV infection in PSCC. It does not show prognostic value for cancer-specific survival and overall survival in PSCC.
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http://dx.doi.org/10.1136/jclinpath-2011-200638DOI Listing
June 2012

Comparison of seven tests for high-grade cervical intraepithelial neoplasia in women with abnormal smears: the Predictors 2 study.

J Clin Microbiol 2012 Jun 14;50(6):1867-73. Epub 2012 Mar 14.

Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary, University of London, London, United Kingdom.

High-risk human papillomavirus (HPV) DNA/RNA testing provides higher sensitivity but lower specificity than cytology for the identification of high-grade cervical intraepithelial neoplasia (CIN). Several new HPV tests are now available for this purpose, and a direct comparison of their properties is needed. Seven tests were evaluated with samples in liquid PreservCyt transport medium from 1,099 women referred for colposcopy: the Hybrid Capture 2 (Qiagen), Cobas (Roche), PreTect HPV-Proofer (NorChip), Aptima HPV (Gen-Probe), and Abbott RealTime assays, the BD HPV test, and CINtec p16(INK4a) cytology (mtm laboratories) immunocytochemistry. Sensitivity, specificity, and positive predictive value (PPV) were based on the worst histology found on either the biopsy or the treatment specimen after central review. Three hundred fifty-nine women (32.7%) had CIN grade 2+ (CIN2+), with 224 (20.4%) having CIN3+. For detection of CIN2+, Hybrid Capture 2 had 96.3% sensitivity, 19.5% specificity, and 37.4% PPV. Cobas had 95.2% sensitivity, 24.0% specificity, and 37.6% PPV. The BD HPV test had 95.0% sensitivity, 24.2% specificity, and 37.8% PPV. Abbott RealTime had 93.3% sensitivity, 27.3% specificity, and 38.2% PPV. Aptima had 95.3% sensitivity, 28.8% specificity, and 39.3% PPV. PreTect HPV-Proofer had 74.1% sensitivity, 70.8% specificity, and 55.4% PPV. CINtec p16(INK4a) cytology had 85.7% sensitivity, 54.7% specificity, and 49.1% PPV. Cytology of a specimen taken at colposcopy (mild dyskaryosis or worse) had 88.9% sensitivity, 58.1% specificity, and 50.7% PPV. Our study confirms that, in a referral setting, HPV testing by a number of different tests provides high sensitivity for high-grade disease. Further work is needed to confirm these findings in a routine screening setting.
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http://dx.doi.org/10.1128/JCM.00181-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3372127PMC
June 2012

Predictive value of symptoms for ovarian cancer: comparison of symptoms reported by questionnaire, interview, and general practitioner notes.

J Natl Cancer Inst 2012 Jan 13;104(2):114-24. Epub 2012 Jan 13.

Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Background: Because of the poor survival outcomes associated with advanced ovarian cancer, early detection strategies are needed. Although several symptom indices have been described, their relationship with the potential lead time has been poorly documented.

Methods: Women aged 50-79 years who had newly diagnosed ovarian cancer (n = 194) and control subjects (n = 268) who attended ovarian cancer screening clinics were included in the analysis. Symptoms and their onset dates were obtained from three sources: a questionnaire (191 case patients and 268 control subjects), telephone interview (111 case patients and 125 control subjects), and general practitioner (GP) notes (171 case patients and 227 control subjects). Data from questionnaires and GP notes were used to derive two new symptom indices (Index 1 and Index 2). Sensitivity and specificity for these new indices and the previously reported Goff index were calculated for the periods of 0-11 and 3-14 months before diagnosis for all three data sources.

Results: For each data source and period, the two new symptom indices derived from questionnaire and GP notes were similar both qualitatively (symptoms included) and quantitatively (sensitivity and specificity) to the Goff index. When symptoms that started within 3 months before diagnosis were excluded, sensitivity was decreased for all indices and all data sources (eg, for telephone interviews, sensitivity for the period 0-11 vs 3-14 months before diagnosis: for Index 1 = 91.0% vs 69.4%, difference = 21.6%, 95% confidence interval [CI] = 13.6% to 29.7%; for Index 2 = 91.0% vs 60.4%, difference = 30.6%, 95% CI = 21.7% to 39.6%; and for the Goff index = 75.7% vs 51.4%, difference = 24.3%, 95% CI = 16.0% to 32.7%). Also, the specificity of all indices was consistently decreased for telephone interviews compared with questionnaires and GP notes (eg, 1 - specificity for the period of 3-14 months before diagnosis for telephone interviews vs questionnaires: for Index 1 = 19.2% vs 10.4%, difference = 8.8%, 95% CI = 1.0% to 16.6%; for Index 2 = 14.4% vs 6.7%, difference = 7.7%, 95% CI = 0.9% to 14.5%; and for the Goff Index = 7.2% vs 1.5%, difference = 5.7%, 95% CI = 0.9% to 10.5%).

Conclusions: Previous estimates of index performance have been overly optimistic because they did not take into account the time required to make a diagnosis on the basis of testing in response to symptoms. In addition, the specificity of a symptom index is lower when based on a telephone interview vs questionnaire or GP notes. Thus, the clinical utility of a symptom index depends on precisely how it is used and how index-positive women are managed.
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http://dx.doi.org/10.1093/jnci/djr486DOI Listing
January 2012

Effect of baseline serum vitamin D levels on aromatase inhibitors induced musculoskeletal symptoms: results from the IBIS-II, chemoprevention study using anastrozole.

Breast Cancer Res Treat 2012 Apr 25;132(2):625-9. Epub 2011 Dec 25.

Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London EC1M 6BQ, UK.

Severe deficiency of vitamin D in adults can cause musculoskeletal pain, stiffness, and joint discomfort. Musculoskeletal symptoms similar to those associated with vitamin D deficiency are frequently seen in breast cancer patients receiving adjuvant aromatase inhibitors (AIs). This is presumably due to oestrogen deficiency caused by AIs. However, no data are available on serum levels of vitamin D and their relation to developing musculoskeletal symptoms/arthralgia in women receiving an AI. IBIS-II is a multicentre randomized placebo controlled trial of the AI, anastrozole, in postmenopausal women aged 40-70 years, who are at increased risk of breast cancer. Serum vitamin D levels were measured for 416 participants. The samples were sent for assays in three batches: the first two batches (n = 250) included paired serum samples and the third batch (n = 166) included paired samples and samples from women who had arthralgia within the first year of follow-up. At entry, 56 (13%) women had adequate (≥ 30 ng/ml), 173 (41%) had inadequate (≥ 20-< 30 ng/mL), 167 (40%) were deficient (> 10-< 20 ng/mL), and 24 (6%) were severely deficient (< 10 ng/mL). At the time of analysis, 225 out of 834 (27%) women had reported arthralgia within the first year of follow-up. Baseline serum vitamin D levels did not significantly predict arthralgia within the first year of follow-up either in the overall group (OR 0.87 (95% CI: 0.67, 1.13; P = 0.30) or separately in the anastrozole (P = 0.60) or placebo groups (P = 0.38). Absolute serum levels of vitamin D increased significantly at one year in the anastrozole group (2.88 ng/ml, [1.71, 4.06; P < 0.0001]) but not in the placebo group (0.75 ng/ml [-0.35, 1.85; P = 0.18]). Only a small and a nonsignificant effect of baseline vitamin D levels were seen on the risk of musculoskeletal symptoms. This does not appear to be a major determinant of risk for these symptoms.
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http://dx.doi.org/10.1007/s10549-011-1911-6DOI Listing
April 2012

Single negative colposcopy: is it enough to rule out high-grade disease?

J Med Screen 2011 ;18(3):160-1

Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary's School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, UK.

It has been proposed that women who have a negative colposcopic examination or who have no cervical intraepithelial neoplasia (CIN) on colposcopic biopsy can be safely returned to routine screening with the next visit being three or five years later. We present data regarding 551 women who had colposcopy in Wales for a low-grade cytological abnormality and who were followed through Cervical Screening Wales for subsequent CIN. Of 436 women declared CIN free initially, 26 (6.0%) had high-grade CIN diagnosed on follow-up. We suggest that additional screening at an interval of less than three years should be offered to women with a negative colposcopy or a biopsy without CIN.
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http://dx.doi.org/10.1258/jms.2011.011097DOI Listing
March 2012

Alternative HER/PTEN/Akt pathway activation in HPV positive and negative penile carcinomas.

PLoS One 2011 Mar 2;6(3):e17517. Epub 2011 Mar 2.

Centre for Molecular Oncology and Imaging, Institute of Cancer, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.

Background: The pathogenesis of penile squamous cell carcinoma (PSCC) is not well understood, though risk factors include human papillomavirus (HPV). Disruption of HER/PTEN/Akt pathway is present in many cancers; however there is little information on its function in PSCC. We investigated HER family receptors and phosphatase and tension homolog (PTEN) in HPV-positive and negative PSCC and its impact on Akt activation using immunohistochemistry and fluorescent in situ hybridisation (FISH).

Methodology/principal Findings: 148 PSCCs were microarrayed and immunostained for phosphorylated EGFR (pEGFR), HER2, HER3, HER4, phosphorylated Akt (pAkt), Akt1 and PTEN proteins. EGFR and PTEN gene status were also evaluated using FISH. HPV presence was assessed by PCR. pEGFR expression was detected significantly less frequently in HPV-positive than HPV-negative tumours (p = 0.0143). Conversely, HER3 expression was significantly more common in HPV-positive cases (p = 0.0128). HER4, pAkt, Akt and PTEN protein expression were not related to HPV. HER3 (p = 0.0054) and HER4 (p = 0.0002) receptors significantly correlated with cytoplasmic Akt1 immunostaining. All three proteins positively correlated with tumour grade (HER3, p = 0.0029; HER4, p = 0.0118; Akt1, p = 0.0001). pEGFR expression correlated with pAkt but not with tumour grade or stage. There was no EGFR gene amplification. HER2 was not detected. PTEN protein expression was reduced or absent in 62% of tumours but PTEN gene copy loss was present only in 4% of PSCCs.

Conclusions/significance: EGFR, HER3 and HER4 but not HER2 are associated with penile carcinogenesis. HPV-negative tumours tend to express significantly more pEGFR than HPV-positive cancers and this expression correlates with pAkt protein, indicating EGFR as an upstream regulator of Akt signalling in PSCC. Conversely, HER3 expression is significantly more common in HPV-positive cases and positively correlates with cytoplasmic Akt1 expression. HER4 and PTEN protein expression are not related to HPV infection. Our results suggest that PSCC patients could benefit from therapies developed to target HER receptors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0017517PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3047574PMC
March 2011
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