16/18 genotyping in triage of persistent human papillomavirus infections with negative cytology in the English cervical screening pilot.

BACKGROUND: In the English pilot of primary cervical screening with high-risk human papillomavirus (HR-HPV), we exploited natural viral clearance over 24 months to minimise unnecessary referral of HR-HPV+ women with negative cytology. Three laboratories were permitted to use 16/18 genotyping to select women for referral at 12-month recall. We estimated the clinical impact of this early genotyping referral. METHODS: The observed numbers of women referred to colposcopy and with detected high-grade cervical intraepithelial neoplasia (CIN2+), and of women who did not attend early recall in the three laboratories were compared with those estimated to represent a situation without an early genotyping referral. The 95% confidence intervals (CI) for the differences between the protocols were calculated by using a parametric bootstrap. RESULTS: Amongst 127,238 screened women, 16,097 (13%) had HR-HPV infections. The genotyping protocol required 5.9% (95% CI: 4.4-7.7) additional colposcopies and led to a detection of 1.2% additional CIN2+ (95% CI: 0.6-2.0), while 2.3% (95% CI: 2.1-2.5) fewer HR-HPV+/cytology- women did not attend the early recall compared with the non-genotyping protocol. CONCLUSIONS: In a screening programme with high quality of triage cytology and high adherence to early recall,16/18 genotyping of persistent HPV infections does not substantially increase CIN2+ detection.

Primary cervical screening with high risk human papillomavirus testing: observational study.

OBJECTIVE: To provide the first report on the main outcomes from the prevalence and incidence rounds of a large pilot of routine primary high risk human papillomavirus (hrHPV) testing in England, compared with contemporaneous primary liquid based cytology screening. DESIGN: Observational study. SETTING: The English Cervical Screening Programme. PARTICIPANTS: 578 547 women undergoing cervical screening in primary care between May 2013 and December 2014, with follow-up until May 2017; 183 970 (32%) were screened with hrHPV testing. INTERVENTIONS: Routine cervical screening with hrHPV testing with liquid based cytology triage and two early recalls for women who were hrHPV positive and cytology negative, following the national screening age and interval recommendations. MAIN OUTCOME MEASURES: Frequency of referral for a colposcopy; adherence to early recall; and relative detection of cervical intraepithelial neoplasia grade 2 or worse from hrHPV testing compared with liquid based cytology in two consecutive screening rounds. RESULTS: Baseline hrHPV testing and early recall required approximately 80% more colposcopies, (adjusted odds ratio 1.77, 95% confidence interval 1.73 to 1.82), but detected substantially more cervical intraepithelial neoplasia than liquid based cytology (1.49 for cervical intraepithelial neoplasia grade 2 or worse, 1.43 to 1.55; 1.44 for cervical intraepithelial neoplasia grade 3 or worse, 1.36 to 1.51) and for cervical cancer (1.27, 0.99 to 1.63). Attendance at early recall and colposcopy referral were 80% and 95%, respectively. At the incidence screen, the 33 506 women screened with hrHPV testing had substantially less cervical intraepithelial neoplasia grade 3 or worse than the 77 017 women screened with liquid based cytology (0.14, 0.09 to 0.23). CONCLUSIONS: In England, routine primary hrHPV screening increased the detection of cervical intraepithelial neoplasia grade 3 or worse and cervical cancer by approximately 40% and 30%, respectively, compared with liquid based cytology. The very low incidence of cervical intraepithelial neoplasia grade 3 or worse after three years supports extending the screening interval.

'Herpes present' reported in a routine cervical cytology and how to deal with it.

In spite of advances in processing and interpreting liquid based cervical cytology, the reliability of diagnosing genital herpes from cervical cytology specimens is disputed. This letter highlights the issues when 'herpes present' is reported in routine smears taken from asymptomatic women.

The effects of a graduated aerobic exercise programme on cardiovascular disease risk factors in the NHS workplace: a randomised controlled trial.

BACKGROUND: Sufficient levels of physical activity provide cardio-protective benefit. However within developed society sedentary work and inflexible working hours promotes physical inactivity. Consequently to ensure a healthy workforce there is a requirement for exercise strategies adaptable to occupational time constraint. This study examined the effect of a 12 week aerobic exercise training intervention programme implemented during working hours on the cardiovascular profile of a sedentary hospital workforce. METHODS: Twenty healthy, sedentary full-time staff members of the North West London Hospital Trust cytology unit were randomly assigned to an exercise (n = 12; mean +/- SD age 41 +/- 8 years, body mass 69 +/- 12 kg) or control (n = 8; mean +/- SD age 42 +/- 8 years, body mass 69 +/- 12 kg) group. The exercise group was prescribed a progressive aerobic exercise-training programme to be performed 4 times a week for 8 weeks (initial intensity 65% peak oxygen consumption (VO2 peak)) and to be conducted without further advice for another 4 weeks. The control was instructed to maintain their current physical activity level. Oxygen economy at 2 minutes (2minVO2), 4 minutes (4minVO2), VO2 peak, systolic blood pressure (SBP), diastolic blood pressure (DBP), BMI, C-reactive protein (CRP), fasting glucose (GLU) and total cholesterol (TC) were determined in both groups pre-intervention and at 4 week intervals. Both groups completed a weekly Leisure Time Questionnaire to quantify additional exercise load. RESULTS: The exercise group demonstrated an increase from baseline for VO2 peak at week 4 (5.8 +/- 6.3 %) and 8 (5.0 +/- 8.7 %) (P < 0.05). 2minVO2 was reduced from baseline at week 4 (-10.2 +/- 10.3 %), 8 (-16.8 +/- 10.6 %) and 12 (-15.1 +/- 8.7 %), and 4minVO2 at week 8 (-10.7 +/- 7.9 %) and 12 (-6.8 +/- 9.2) (P < 0.05). There was also a reduction from baseline in CRP at week 4 (-0.4 +/- 0.6 mg.L-1) and 8 (-0.9 +/- 0.8 mg.L-1) (P < 0.05). The control group showed no such improvements. CONCLUSION: This is the first objectively monitored RCT to show that moderate exercise can be successfully incorporated into working hours, to significantly improve physical capacity and cardiovascular health.

Idiopathic intimal hyperplasia of small arteries and arterioles affecting intestines and myocardium.

We report the case of a 52-year-old woman dying from a noninflammatory, occlusive vasculopathy. Histology showed marked intimal hyperplasia of small arteries of the intestines and myocardium with subsequent infarction of myocardium, large intestine and gallbladder. A comprehensive work up including laboratory studies, clinical investigations and postmortem failed to assign this condition to any of the known vascular diseases.