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BackgroundIn the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance.MethodologyWe report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context.Principal FindingsBoth in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations.ConclusionsIt is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events.Trial registrationClinicalTrials.gov NCT02017899, NCT02034500, NCT01771367, NCT01765413, NCT02523287

Out-patient treatment of precancerous lesions of the cervix usually results in clearance of HPV. Both LEEP and cryotherapy are highly effective methods of eradicating HPV. HPV DNA testing may have added value in the follow-up of patients.

Bivalent (GI.1 and GII.4) virus-like particle norovirus candidate vaccine formulations were well tolerated and immunogenic, 1 dose inducing immune responses that persisted up to 1 year, which were not increased by inclusion of monophosphoryl lipid A or administration of a second dose.

Prediction of recurrent disease by cytology and HPV testing after treatment of cervical intraepithelial neoplasiaObjective: To assess the role of human papillomavirus (HPV) testing and cytology as predictors of residual ⁄ recurrent disease after treatment of high-grade cervical intraepithelial lesions. Methods: One hundred and thirty-eight women with cervical intraepithelial neoplasia (CIN) grade 2 ⁄ 3 lesion on biopsy were included in a prospective follow-up study in Belgium and Nicaragua. All women were treated with loop electrosurgical excision procedure (LEEP) and follow-up visits took place at 6 weeks, 6 months, 1 year and 2 years. During these visits, a Papanicolaou (Pap) smear test was taken, colposcopy was performed and specimens were collected for HPV testing. Cytology, high-risk (HR) HPV presence, persistent HR HPV infection and combinations of these tests at different time points during follow-up were correlated with histologically confirmed residual ⁄ recurrent disease. Results: Thirteen patients (9%) developed residual ⁄ recurrent disease during follow-up. Abnormal cytology at 6 weeks after treatment was significantly correlated with residual ⁄ recurrent disease. Nine of thirty-seven patients with abnormal cytology at 6 weeks had recurrent disease versus three of seventy with a normal cytology [odds ratio (OR): 7.2; 95% confidence interval (CI): 1.8-28.5; P = 0.003). Sensitivity of this test was 75.0%, specificity 70.5%. Combining abnormal cytology and the presence of HR HPV within the first 6 months after treatment gave the best correlation with residual ⁄ recurrent disease: of the 54 women with abnormal cytology and ⁄ or HR HPV presence within the first 6 months, 11 developed residual ⁄ recurrent disease (OR 10.2; 95% CI: 2.2-48.3). Sensitivity of this combination was 84.6% and specificity 65.0%. Conclusion: Cytology remains the cornerstone in the early follow-up after LEEP for CIN lesions of the cervix. HPV testing can add value as it increases the sensitivity of cytology in concomitant testing within the first 6 months.