Lectins in Cervical Screening.

Cervical screening in low-resource settings remains an unmet need. Lectins are naturally occurring sugar-binding glycoproteins whose binding patterns change as cancer develops. Lectins discriminate between dysplasia and normal tissue in several precancerous conditions. We explored whether lectins could be developed for cervical screening via visual inspection. Discovery work comprised lectin histochemistry using a panel of candidate lectins on fixed-human cervix tissue (high-grade cervical intraepithelial neoplasia (CIN3, n = 20) or normal (n = 20)), followed by validation in a separate cohort (30 normal, 25 CIN1, 25 CIN3). Lectin binding was assessed visually according to staining intensity. To validate findings macroscopically, near-infra red fluorescence imaging was conducted on freshly-resected cervix (1 normal, 7 CIN3), incubated with topically applied fluorescently-labelled lectin. Fluorescence signal was compared for biopsies and whole specimens according to regions of interest, identified by the overlay of histopathology grids. Lectin histochemistry identified two lectins-wheat germ agglutinin (WGA) and Helix pomatia agglutinin (HPA)-with significantly decreased binding to CIN3 versus normal in both discovery and validation cohorts. Findings at the macroscopic level confirmed weaker WGA binding (lower signal intensity) in CIN3 vs. normal for biopsies (p = 0.0308) and within whole specimens (p = 0.0312). Our findings confirm proof-of-principle and indicate that WGA could potentially be developed further as a probe for high-grade cervical disease

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Lectins in Cervical Screening

Cervical screening in low-resource settings remains an unmet need. Lectins are naturally occurring sugar-binding glycoproteins whose binding patterns change as cancer develops. Lectins discriminate between dysplasia and normal tissue in several precancerous conditions. We explored whether lectins could be developed for cervical screening via visual inspection. Discovery work comprised lectin histochemistry using a panel of candidate lectins on fixed-human cervix tissue (high-grade cervical intraepithelial neoplasia (CIN3, n = 20) or normal (n = 20)), followed by validation in a separate cohort (30 normal, 25 CIN1, 25 CIN3). Lectin binding was assessed visually according to staining intensity. To validate findings macroscopically, near-infra red fluorescence imaging was conducted on freshly-resected cervix (1 normal, 7 CIN3), incubated with topically applied fluorescently-labelled lectin. Fluorescence signal was compared for biopsies and whole specimens according to regions of interest, identified by the overlay of histopathology grids. Lectin histochemistry identified two lectins—wheat germ agglutinin (WGA) and Helix pomatia agglutinin (HPA)—with significantly decreased binding to CIN3 versus normal in both discovery and validation cohorts. Findings at the macroscopic level confirmed weaker WGA binding (lower signal intensity) in CIN3 vs. normal for biopsies (p = 0.0308) and within whole specimens (p = 0.0312). Our findings confirm proof-of-principle and indicate that WGA could potentially be developed further as a probe for high-grade cervical disease

Cytology in the diagnosis of cervical cancer in symptomatic young women: a retrospective review

This work was supported by Cancer Research UK [C8162/A16892]

Non-speculum clinician-taken samples for human papillomavirus testing:a cross-sectional study in older women

BACKGROUND: Cervical cancer incidence and mortality are high in women aged ≥65 years, despite the disease being preventable by screening. Speculum-based screening can become more uncomfortable after the menopause. AIM: To examine test performance and acceptability of human papillomavirus (HPV) testing on clinician-collected vaginal samples without a speculum (non-speculum). DESIGN AND SETTING: Cross-sectional study in 11 GP practices and four colposcopy clinics in London, UK, between August 2017 and January 2019. METHOD: Non-speculum and conventional (speculum) samples were collected from women aged ≥50 years attending for a colposcopy (following a speculum HPV-positive screening result) or women aged ≥35 years (with confirmed cervical intraepithelial neoplasia (CIN) 2+), and women aged 50–64 years attending routine screening. Sensitivity to CIN2+ was assessed among women with confirmed CIN2+ (colposcopy). Specificity to HPV relative to speculum sampling and overall concordance was assessed among women with negative cytology (routine screening). RESULTS: The sensitivity of non-speculum sampling for detecting CIN2+ was 83.3% (95% confidence interval [CI] = 60.8 to 94.2) (n = 15/18). There was complete concordance among women with positive CIN2+ who had a speculum sample ≤91 days prior to the non-speculum sample (n = 12). Among 204 women with negative cytology, the specificity to HPV was 96.4% (95% CI = 92.7 to 98.5), with 96.6% concordant results (κ 72.4%). Seventy-one percent (n = 120/170) of women preferred a non-speculum sample for their next screen. CONCLUSION: HPV testing on non-speculum clinician-taken samples is a viable approach that warrants further exploration in larger studies. Overall test performance was broadly comparable with that of self-sampling