Timothy Palmer

Reduction of low- and high-grade cervical abnormalities associated with high uptake of the HPV bivalent vaccine in Scotland

Background:In Scotland, a national HPV immunisation programme began in 2008 for 12- to 13-year olds, with a catch-up campaign from 2008 to 2011 for those under the age of 18. To monitor the impact of HPV immunisation on cervical disease at the population level, a programme of national surveillance was established.Methods:We analysed colposcopy data from a cohort of women born between 1988 and 1992 who entered the Scottish Cervical Screening Programme (SCSP) and were aged 20–21 in 2008–2012.Results:By linking datasets from the SCSP and colposcopy services, we observed a significant reduction in diagnoses of cervical intraepithelial neoplasia 1 (CIN 1; RR 0.71, 95% CI 0.58 to 0.87; P=0.0008), CIN 2 (RR 0.5, 95% CI 0.4 to 0.63; P<0.0001) and CIN 3 (RR 0.45, 95% CI 0.35 to 0.58; P<0.0001) for women who received three doses of vaccine compared with unvaccinated women.Conclusions:To our knowledge, this is one of the first studies to show a reduction of low- and high-grade CIN associated with high uptake of the HPV bivalent vaccine at the population level. These data are very encouraging for countries that have achieved high HPV vaccine uptake.

Triage of HPV positive women in cervical cancer screening.

Despite HPV vaccines, screening will remain central for decades to control cervical cancer. Recently, HPV testing alone or with cytology was introduced as an alternative to cytology screening. However, most HPV infections are harmless and additional tests are required to identify women with progressing infections or precancer. With three options for primary screening, and without clear strategies for triage of screen-positive women, there is great confusion about the best approach. Also, increasing HPV vaccination coverage will lead to lower disease prevalence, and force new screening approaches. Currently recommended triage strategies for primary HPV screening include HPV genotyping for HPV16 and HPV18 and cytology. Other alternatives that are currently evaluated include p16/Ki-67 dual stain cytology, host methylation, and viral methylation testing. Clinical management of women with cervical cancer screening results is moving to use risk thresholds rather than individual test results. Specific risk thresholds have been defined for return to primary screening, repeat testing, referral to colposcopy, and immediate treatment. Choice of test algorithms is based on comparison of absolute risk estimates from triage tests with established clinical thresholds. Importantly, triage tests need to be evaluated together with the primary screening test and the downstream clinical management. An optimal integrated screening and triage strategy should reassure the vast majority of women that they are at very low risk of cervical cancer, send the women at highest risk to colposcopy at the right time, when disease can be colposcopically detected, and minimize the intermediate risk group that requires continued surveillance.

Human Papillomavirus Prevalence and Herd Immunity after Introduction of Vaccination Program, Scotland, 2009-2013

Prevalence was reduced, and early evidence indicates herd immunity.

Seeding of tumor cells after fine needle aspiration cytology in benign parotid tumor: a case report and literature review.

Fine needle aspiration cytology (FNAC) is generally considered a safe, sensitive, and specific diagnostic tool and is widely used for various clinical indications. However, some authors have raised concerns regarding the possibility of tumor cell seeding along the needle track. We present to our knowledge the first case of tumor seeding after FNAC of a benign parotid tumor. This is followed by a review of the literature on tumor seeding after aspiration with fine needles of 20 gauge and smaller and the implications for clinical practice.

Changes in the prevalence of human papillomavirus following a national bivalent human papillomavirus vaccination programme in Scotland: a 7-year cross-sectional study

BACKGROUND On Sept 1, 2008, Scotland launched routine vaccination for human papillomavirus (HPV) types 16 and 18, targeted at 12-13-year-old girls, of whom 92·4% were fully vaccinated in 2008-09. In this study, we report on vaccine effectiveness of the bivalent vaccine in these vaccinated women who attended for routine cervical screening at age 20-21 years. METHODS In this 7-year cross-sectional study (covering birth cohorts 1988-1995), we sampled approximately 1000 samples per year from those attending cervical screening at age 20-21 years and tested each for HPV. By linkage to vaccination records we ascertained prevalence by birth cohort and vaccination status. Estimates of vaccine effectiveness for HPV types 16 and 18, HPV types 31, 33, and 45, other high-risk types, and any HPV were calculated using logistic regression. FINDINGS In total, 8584 samples were HPV genotyped. Prevalence of HPV types 16 and 18 reduced substantially from 30·0% (95% CI 26·9-33·1) in the 1988 cohort to 4·5% (3·5-5·7) in the 1995 cohort, giving a vaccine effectiveness of 89·1% (85·1-92·3) for those vaccinated at age 12-13 years. All cross-protective types showed significant vaccine effectiveness (HPV type 31, 93·8% [95% CI 83·8-98·5]; HPV type 33, 79·1% [64·2-89·0]; HPV type 45, 82·6% [61·5-93·9]). Unvaccinated individuals born in 1995 had a reduced odds of HPV types 16 and 18 infection compared with those born in 1988 (adjusted odds ratio 0·13 [95% CI 0·06-0·28]) and reduced odds of HPV types 31, 33, and 45 (odds ratio 0·45 [0·23-0·89]). INTERPRETATION Bivalent vaccination has led to a startling reduction in vaccine and cross-protective HPV types 7 years after vaccination. There is also evidence of herd protection against the vaccine-specific and cross-protective types in unvaccinated individuals born in 1995. These findings should be considered in cost-effectiveness models informing vaccine choice and models to shape the future of cervical screening programmes. FUNDING Scottish Government and Chief Scientists Office.

HPV immunisation and cervical screening--confirmation of changed performance of cytology as a screening test in immunised women: a retrospective population-based cohort study.

Background:To document the effect of bivalent HPV immunisation on cervical cytology as a screening test and assess the implications of any change, using a retrospective analysis of routinely collected data from the Scottish Cervical Screening Programme (SCSP).Methods:Data were extracted from the Scottish Cervical Call Recall System (SCCRS), the Scottish Population Register and the Scottish Index of Multiple Deprivation. A total of 95 876 cytology records with 2226 linked histology records from women born between 1 January 1988 and 30 September 1993 were assessed. Women born in or after 1990 were eligible for the national catch-up programme of HPV immunisation. The performance of cervical cytology as a screening test was evaluated using the key performance indicators used routinely in the English and Scottish Cervical Screening Programmes (NHSCSP and SCSP), and related to vaccination status.Results:Significant reductions in positive predictive value (16%) and abnormal predictive value (63%) for CIN2+ and the mean colposcopy score (18%) were observed. A significant increase (38%) in the number of women who had to be referred to colposcopy to detect one case of CIN2+ was shown. The negative predictive value of negative- or low-grade cytology for CIN2+ increased significantly (12%). Sensitivity and specificity, as used by the UK cervical screening programmes, were maintained.Conclusions:The lower incidence of disease in vaccinated women alters the key performance indicators of cervical cytology used to monitor the quality of the screening programme. These findings have implications for screening, colposcopy referral criteria, colposcopy practice and histology reporting.

HPV immunisation and increased uptake of cervical screening in Scottish women : observational study of routinely collected national data

Background:To measure the uptake of first invitation to cervical screening by vaccine status in a population-based cohort offered HPV immunisation in a national catch-up campaign.Methods:A retrospective observational study of routinely collected data from the Scottish Cervical Screening Programme. Data were extracted and linked from the Scottish Cervical Call Recall System, the Scottish Population Register and the Scottish Index of Multiple Deprivation. Records from 201 023 women born between 1 January 1988 and 30 September 1993 were assessed. Women born in or after 1990 were eligible for the national catch-up programme of HPV immunisation. Attendance for screening was within 12 months of the first invitation at age 20 years.Results:There was a significant decline in overall attendance from the 1988 cohort to the 1993 cohort with the adjusted attendance ratio of the 1988 cohort being 1.49 times (95% CI 1.46–1.52) that of the 1993 cohort. Immunisation compensated for this decrease in uptake with unvaccinated individuals having a reduced ratio of attendance compared with those fully vaccinated (RR=0.65, 95% CI 0.64–0.65). Not taking up the opportunity for HPV immunisation was associated with an attendance for screening below the trend line for all women before the availability of HPV immunisation.Conclusions:HPV immunisation is not associated with the reduced attendance for screening that had been feared. Immunised women in the catch-up cohorts appear to be more motivated to attend than unimmunised women, but this may be a result of a greater awareness of health issues. These results, while reassuring, may not be reproduced in routinely immunised women. Continued monitoring of attendance for the first smear and subsequent routine smears is needed.

Prospective parallel randomized trial of the MultiCyte™ ThinPrep(®) imaging system: the Scottish experience

T.J. Palmer, S.M. Nicoll, M.E. McKean, A.J. Park, D. Bishop, L. Baker and J.E.A. Imrie 
Prospective parallel randomized trial of the MultiCyte™ ThinPrep® imaging system: the Scottish experience

Use of HPV testing for cervical screening in vaccinated women—Insights from the SHEVa (Scottish HPV Prevalence in Vaccinated Women) study

The management of cervical disease is changing worldwide as a result of HPV vaccination and the increasing use of HPV testing for cervical screening. However, the impact of vaccination on the performance of HPV based screening strategies is unknown. The SHEVa (Scottish HPV Prevalence in Vaccinated women) projects are designed to gain insight into the impact of vaccination on the performance of clinically validated HPV assays. Samples collated from women attending for first cervical smear who had been vaccinated as part of a national “catch‐up” programme were tested with three clinically validated HPV assays (2 DNA and 1 RNA). Overall HR‐HPV and type specific positivity was assessed in total population and according to underlying cytology and compared to a demographically equivalent group of unvaccinated women. HPV prevalence was significantly lower in vaccinated women and was influenced by assay‐type, reducing by 23‐25% for the DNA based assays and 32% for the RNA assay (p = 0.0008). All assays showed over 75% reduction of HPV16 and/or 18 (p < 0.0001) whereas the prevalence of non 16/18 HR‐HPV was not significantly different in vaccinated vs unvaccinated women. In women with low grade abnormalities, the proportion associated with non 16/18 HR‐HPV was significantly higher in vaccinated women (p < 0.0001). Clinically validated HPV assays are affected differentially when applied to vaccinated women, dependent on assay chemistry. The increased proportion of non HPV16/18 infections may have implications for clinical performance, consequently, longitudinal studies linking HPV status to disease outcomes in vaccinated women are warranted.

Type and maturational status of dendritic cells in cutaneous B cell lymphoproliferative disorders

Christie L J, MacKenzie C, Palmer T J, Baker L & Goodlad J R
(2011) Histopathology59, 421–432