Performance of visual inspection of the cervix with acetic acid (VIA) for triage of HPV screen-positive women: results from the ESTAMPA study.

VIA is recommended for triage of HPV-positive women attending cervical screening. In the multicentric ESTAMPA study, VIA performance for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) among HPV-positive women was evaluated. Women aged 30-64 years were screened with HPV testing and cytology and referred to colposcopy if either test was positive. At colposcopy visit, study-trained midwives/nurses/GPs performed VIA ahead of colposcopy. VIA was considered positive if acetowhite lesions were observed in or close to the transformation zone. Ablative treatment eligibility was assessed for VIA positives. Performance indicators were estimated. Three thousand one hundred and forty-two HPV-positive women were included. Sensitivity for CIN3+ was 85.9% (95% CI 81.2-89.5) among women <50 years and, although not significant, slightly lower in women 50+ (78.0%, 95% CI 65.9-86.6). Overall specificity was 58.6% (95% CI 56.7-60.5) and was significantly higher among women 50+ (70.3%, 95% CI 66.8-73.5) compared to women <50 (54.3%, 95% CI 52.1-56.5). VIA positivity was lower among women 50+ (35.2%, 95% CI 31.9-38.6) compared to women <50 (53.2, 95% CI 51.1-55.2). Overall eligibility for ablative treatment was 74.5% and did not differ by age. VIA sensitivity, specificity, and positivity, and ablative treatment eligibility varied highly by provider (ranges: 25%-95.4%, 44.9%-94.4%, 8.2%-65.3%, 0%-98.7%, respectively). VIA sensitivity for cervical precancer detection among HPV-positive women performed by trained providers was high with an important reduction in referral rates. However, scaling-up HPV screening triaged by VIA will be challenging due to the high variability of VIA performance and providers' need for training and supervision.

A comparison of COVID-19 incidence rates across six European countries in 2021.

International comparisons of COVID-19 incidence rates have helped gain insights into the characteristics of the disease, benchmark disease impact, shape public health measures and inform potential travel restrictions and border control measures. However, these comparisons may be biased by differences in COVID-19 surveillance systems and approaches to reporting in each country. To better understand these differences and their impact on incidence comparisons, we collected data on surveillance systems from six European countries: Belgium, England, France, Italy, Romania and Sweden. Data collected included: target testing populations, access to testing, case definitions, data entry and management and statistical approaches to incidence calculation. Average testing, incidence and contextual data were also collected. Data represented the surveillance systems as they were in mid-May 2021. Overall, important differences between surveillance systems were detected. Results showed wide variations in testing rates, access to free testing and the types of tests recorded in national databases, which may substantially limit incidence comparability. By systematically including testing information when comparing incidence rates, these comparisons may be greatly improved. New indicators incorporating testing or existing indicators such as death or hospitalisation will be important to improving international comparisons.

The impact of catch-up bivalent human papillomavirus vaccination on cervical screening outcomes: an observational study from the English HPV primary screening pilot.

BACKGROUND: In England, bivalent vaccination (Cervarix) against high-risk human papillomavirus (HR-HPV) genotypes 16/18 was offered in a population-based catch-up campaign in 2008-2010 to girls aged 14-17 years. These women are now entering the national cervical screening programme. We determined the impact of catch-up bivalent vaccination on their screening outcomes. METHODS: We studied the overall and genotype-specific screening outcomes in 108,138 women aged 24-25 (offered vaccination) and 26-29 years (not offered vaccination) included in the English HPV screening pilot between 2013 and 2018. RESULTS: At 24-25 years, the detection of high-grade cervical intraepithelial neoplasia (CIN2+) associated with HPV16/18 decreased from 3 to 1% (p < 0.001), with estimated vaccine effectiveness of 87% (95% CI: 82-91%). The detection of any CIN2+ halved from 6 to 3% (p < 0.001), with an estimated vaccine effectiveness of 72% (95% CI: 66-77%). The positive predictive value of a colposcopy for CIN2+ decreased for both low-grade (p < 0.001) and high-grade (p = 0.02) abnormalities on triage cytology. The decreases in screen-detected abnormalities at age 26-29 were of a substantially smaller magnitude. CONCLUSIONS: These data confirm high effectiveness of bivalent HPV vaccination delivered through a population-based catch-up campaign in England. These findings add to the rationale for extending screening intervals for vaccinated cohorts.

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.

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.

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

OBJECTIVES: Rectal swab specimens, either alone or pooled with first-void urine (FVU) and pharyngeal swab specimens, are used to test for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (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.

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

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.

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

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.

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.

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.

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

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.

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.

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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).

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

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.

The impact of over ten years of HPV vaccination in England: Surveillance of type-specific HPV in young sexually active females.

INTRODUCTION: The UK national human papillomavirus (HPV) vaccination programme was introduced in 2008 using the bivalent HPV16/18 vaccine, changing to the quadrivalent HPV6/11/16/18 vaccine from 2012. We provide an analysis of type-specific HPV prevalence in young sexually active females in England to end 2020 (when the first routinely HPV vaccinated females were reaching 25 years of age and entering the National Health Service Cervical Screening Programme), showing the impact of over ten years of high coverage HPV vaccination. METHODS: Residual vulvovaginal swabs (VVS) were collected from 16 to 24 year old women attending for chlamydia screening between 2010 and 2020, anonymised and tested for type-specific HPV DNA. Trends in vaccine and non-vaccine HPV type prevalence were compared over time and association with vaccination coverage was evaluated within the post-vaccination period. RESULTS: A total of 21,168 eligible VVS specimens were tested for HPV DNA. The prevalence of HPV16/18 in sexually active 16-18 year old females who were offered vaccination aged 12-13 years was <1% in the most recent years tested, compared to over 15% prior to the vaccination programme in 2008. The magnitude of these decreases also suggests reduced transmission is offering some herd protection to unvaccinated females. HPV31/33/45 prevalence also steadily decreased, providing evidence of cross-protection. HPV6/11 prevalence remained stable during the bivalent vaccine period, with more recent declines, as expected due to the use of the quadrivalent vaccine. There has been no substantive increase in the prevalence of other high-risk (HR) HPV types. DISCUSSION: More than ten years of high coverage HPV vaccination in adolescent females in England has delivered dramatic declines in the prevalence of HPV vaccine-types and closely related HPV types in females in the vaccine eligible age group, and no indication of type replacement. These findings should enable confidence in planning for cervical screening of these females, and in predicting declines in HPV-related cancers.

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

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.