Attendance at cervical cancer screening and use of diagnostic and therapeutic procedures on the uterine cervix assessed from individual health insurance data (Belgium, 2002-2006)

Objective: To assess the coverage for cervical cancer screening as well as the use of cervical cytology, colposcopy and other diagnostic and therapeutic interventions on the uterine cervix in Belgium, using individual health insurance data. Methods: The Intermutualistic Agency compiled a database containing 14 million records from reimbursement claims for Pap smears, colposcopies, cervical biopsies and surgery, performed between 2002 and 2006. Cervical cancer screening coverage was defined as the proportion of women aged 25-64 that had a Pap smear within the last 3 years. Results: Cervical cancer screening coverage was 61% at national level, for the target population of women between 25 and 64 years old, in the period 2004-2006. Differences between the 3 regions were small, but varied more substantially between provinces. Coverage was 70% for 25-34 year old women, 67% for those aged 35-39 years, and decreased to 44% in the age group of 60-64 years. The median screening interval was 13 months. The screening coverage varied substantially by social category: 40% and 64%, in women categorised as beneficiary or not-beneficiary of increased reimbursement from social insurance, respectively. In the 3-year period 2004-2006, 3.2 million screen tests were done in the target group consisting of 2.8 million women. However, only 1.7 million women got one or more smears and 1.1 million women had no smears, corresponding to an average of 1.88 smears per woman in three years of time. Colposcopy was excessively used (number of Pap smears over colposcopies = 3.2). The proportion of women with a history of conisation or hysterectomy, before the age of 65, was 7% and 19%, respectively. Conclusion: The screening coverage increased slightly from 59% in 2000 to 61% in 2006. The screening intensity remained at a high level, and the number of cytological examinations was theoretically sufficient to cover more than the whole target population

Comparative study of the radiosensitising and cell cycle effects of vinflunine and vinorelbine, in vitro

<p>Abstract</p> <p>Background</p> <p>Vinca alkaloids are an important class of anticancer agents and semisynthetic vinca alkaloids are developed to improve the therapeutic index of this class of drugs. In the present study, a direct comparison was made between vinflunine and vinorelbine regarding their radiosensitising and cell cycle effects.</p> <p>Methods</p> <p>Four human tumour cell lines were tested under identical experimental conditions, using equitoxic concentrations of vinflunine and vinorelbine.</p> <p>Results</p> <p>Vinflunine and vinorelbine induced a comparable radiosensitising effect (p-value never below 0.01) when cells were incubated for 24 h immediately prior to radiation. Regarding the cell cycle effects, a statistically significant concentration-dependent G2/M block was seen after 24 h incubation with vinorelbine in all tested cell lines. Similar results, with small cell line-related differences, were observed with vinflunine.</p> <p>Conclusion</p> <p>The radiosensitising effects of both semisynthetic vinca alkaloids were comparable (not statistically different) and nearly always cell line-specific and concentration-dependent. The cell cycle effects could be related to the observed radiosensitising effects. Considering the more favourable toxicity profile of vinflunine, this agent might be more promising than vinorelbine for chemoradiation studies in the clinic.</p

Attendance at cervical cancer screening and use of diagnostic and therapeutic procedures on the uterine cervix assessed from individual health insurance data ( Belgium, 2002-2006)

OBJECTIVE: To assess the coverage for cervical cancer screening as well as the use of cervical cytology, colposcopy and other diagnostic and therapeutic interventions on the uterine cervix in Belgium, using individual health insurance data. METHODS: The Intermutualistic Agency compiled a database containing 14 million records from reimbursement claims for Pap smears, colposcopies, cervical biopsies and surgery, performed between 2002 and 2006. Cervical cancer screening coverage was defined as the proportion of women aged 25–64 that had a Pap smear within the last 3 years. RESULTS: Cervical cancer screening coverage was 61% at national level, for the target population of women between 25 and 64 years old, in the period 2004–2006. Differences between the 3 regions were small, but varied more substantially between provinces. Coverage was 70% for 25–34 year old women, 67% for those aged 35–39 years, and decreased to 44% in the age group of 60–64 years. The median screening interval was 13 months. The screening coverage varied substantially by social category: 40% and 64%, in women categorised as beneficiary or not-beneficiary of increased reimbursement from social insurance, respectively. In the 3-year period 2004–2006, 3.2 million screen tests were done in the target group consisting of 2.8 million women. However, only 1.7 million women got one or more smears and 1.1 million women had no smears, corresponding to an average of 1.88 smears per woman in three years of time. Colposcopy was excessively used (number of Pap smears over colposcopies = 3.2). The proportion of women with a history of conisation or hysterectomy, before the age of 65, was 7% and 19%, respectively. CONCLUSION: The screening coverage increased slightly from 59% in 2000 to 61% in 2006. The screening intensity remained at a high level, and the number of cytological examinations was theoretically sufficient to cover more than the whole target population

Accuracy of high-risk HPV DNA PCR, p16(INK4a) immunohistochemistry or the combination of both to diagnose HPV-driven oropharyngeal cancer

Background: the incidence of high-risk human papillomavirus (hrHPV)-driven head and neck squamous cell carcinoma, in particular oropharyngeal cancers (OPC), is increasing in high-resource countries. Patients with HPV-induced cancer respond better to treatment and consequently have lower case-fatality rates than patients with HPV-unrelated OPC. These considerations highlight the importance of reliable and accurate markers to diagnose truly HPV-induced OPC. Methods: the accuracy of three possible test strategies, i.e. (a) hrHPV DNA PCR (DNA), (b) p16(INK4a) immunohistochemistry (IHC) (p16), and (c) the combination of both tests (considering joint DNA and p16 positivity as positivity criterion), was analysed in tissue samples from 99 Belgian OPC patients enrolled in the HPV-AHEAD study. Presence of HPV E6*I mRNA (mRNA) was considered as the reference, indicating HPV etiology. Results: ninety-nine OPC patients were included, for which the positivity rates were 36.4%, 34.0% and 28.9% for DNA, p16 and mRNA, respectively. Ninety-five OPC patients had valid test results for all three tests (DNA, p16 and mRNA). Using mRNA status as the reference, DNA testing showed 100% (28/28) sensitivity, and 92.5% (62/67) specificity for the detection of HPV-driven cancer. p16 was 96.4% (27/28) sensitive and equally specific (92.5%; 62/67). The sensitivity and specificity of combined p16 + DNA testing was 96.4% (27/28) and 97.0% (65/67), respectively. In this series, p16 alone and combined p16 + DNA missed 1 in 28 HPV driven cancers, but p16 alone misclassified 5 in 67 non-HPV driven as positive, whereas combined testing would misclassify only 2 in 67. Conclusions: single hrHPV DNA PCR and p16(INK4a) IHC are highly sensitive but less specific than using combined testing to diagnose HPV-driven OPC patients. Disease prognostication can be encouraged based on this combined test result.The global HPV-AHEAD study was initially funded by the European Commission, with Grant Number: FP7-HEALTH-2011-282562. Sciensano, the employer of CS and MA, received funding for the analysis of the Belgian part of the HPV-AHEAD study, in part, by a research grant from the Investigator Initiated Studies Program of Merck Sharp & Dohme Corp. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme Corp. MA was also supported by the Horizon 2020 Framework Programme for Research and Innovation of the European Commission, through the RISCC Network (Grant No. 847845); and the Belgian Foundation Against Cancer through the IHUVACC project

The positive predictive value of high-grade squamous intraepithelial lesion on cytology for the histological diagnosis of cervical intraepithelial neoplasia 2 or higher : a systematic review

Cervical cancer is a major worldwide health problem. Therefore, regular cervical screening in order to make an early diagnosis can help to prevent cervical cancer, through identifying and treating preinvasive cervical lesions. The aim of this review is to evaluate the correlation between the cytological screening result and the final gold standard histological outcome in the diagnosis of cervical lesions. More specifically, the correlation between high-grade intraepithelial lesion (HSIL) on cytology and histological cervical intraepithelial neoplasia grade 2 or higher (CIN2+) was intended, by calculating the positive predictive value (PPV). PPV is an important value from a clinical point of view. An electronic search was carried out in the electronic databases MEDLINE (through PubMed) and the Cochrane Library (last searched beginning of December 2017), supplemented with the related article feature in PubMed and snowballing. Article selection (predefined inclusion and exclusion criteria) and data extraction were evaluated by two independent reviewers (N.K. and A.V.L.). After identifying 1,146 articles, 27 articles were finally included in this systematic review, representing 28,783 cytological HSIL diagnoses in total. The PPV of HSIL was 77.5% (range: 45.4-95.2%) for the histological diagnosis of CIN2+ and 55.4% (range: 36.4-67.6%) for the diagnosis of CIN3+. In this systematic review, 77.5% of the HSIL-positive women eventually had a CIN2+ diagnosis. The diagnostic value of a cytological HSIL result (conventional or liquid-based cytology) in the diagnosis of CIN2+ lesions is good, but a combination of tests could raise this value. (C) 2019 S. Karger AG, Base

Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors

Background Persistent infection with high-risk human papillomaviruses (hrHPV) types is causally linked with the development of cervical precancer and cancer. HPV types 16 and 18 cause approximately 70% of cervical cancers worldwide. Objectives To evaluate the harms and protection of prophylactic human papillomaviruses (HPV) vaccines against cervical precancer and HPV16/18 infection in adolescent girls and women. Search methods We searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and Embase (June 2017) for reports on effects from trials. We searched trial registries and company results' registers to identify unpublished data for mortality and serious adverse events. Selection criteria Randomised controlled trials comparing efficacy and safety in females offered HPV vaccines with placebo (vaccine adjuvants or another control vaccine). Data collection and analysis We used Cochrane methodology and GRADE to rate the certainty of evidence for protection against cervical precancer (cervical intraepithelial neoplasia grade 2 and above [CIN2(+)], CIN grade 3 and above [CIN3(+)], and adenocarcinoma-in-situ [AIS]), and for harms. We distinguished between the effects of vaccines by participants' baseline HPV DNA status. The outcomes were precancer associated with vaccine HPV types and precancer irrespective of HPV type. Results are presented as risks in control and vaccination groups and risk ratios (RR) with 95% confidence intervals in brackets. Main results We included 26 trials (73,428 participants). Ten trials, with follow-up of 1.3 to 8 years, addressed protection against CIN/AIS. Vaccine safety was evaluated over a period of 6 months to 7 years in 23 studies. Studies were not large enough or of sufficient duration to evaluate cervical cancer outcomes. All but one of the trials was funded by the vaccine manufacturers. We judged most included trials to be at low risk of bias. Studies involved monovalent (N = 1), bivalent (N = 18), and quadrivalent vaccines (N = 7). Most women were under 26 years of age. Three trials recruited women aged 25 and over. We summarize the effects of vaccines in participants who had at least one immunisation. Efficacy endpoints by initial HPV DNA statushr HPV negative HPV vaccines reduce CIN2(+), CIN3(+), AIS associated with HPV16/18 compared with placebo in adolescent girls and women aged 15 to 26. There is high-certainty evidence that vaccines lower CIN2(+) from 164 to 2/10,000 (RR 0.01 (0 to 0.05)) and CIN3(+) from 70 to 0/10,000 (RR 0.01 (0.00 to 0.10). There is moderate-certainty evidence that vaccines reduce the risk of AIS from 9 to 0/10,000 (RR 0.10 (0.01 to 0.82). HPV vaccines reduce the risk of any CIN2(+) from 287 to 106/10,000 (RR 0.37 (0.25 to 0.55), high certainty) and probably reduce any AIS lesions from 10 to 0/10,000 (RR 0.1 (0.01 to 0.76), moderate certainty). The size of reduction in CIN3(+) with vaccines differed between bivalent and quadrivalent vaccines (bivalent: RR 0.08 (0.03 to 0.23), high certainty; quadrivalent: RR 0.54 (0.36 to 0.82), moderate certainty). Data in older women were not available for this comparison. HPV16/18 negative In those aged 15 to 26 years, vaccines reduce CIN2(+) associated with HPV16/18 from 113 to 6 /10,000 (RR 0.05 (0.03 to 0.10). In women 24 years or older the absolute and relative reduction in the risk of these lesions is smaller (from 45 to 14/10,000, (RR 0.30 (0.11 to 0.81), moderate certainty). HPV vaccines reduce the risk of CIN3(+) and AIS associated with HPV16/18 in younger women (RR 0.05 (0.02 to 0.14), high certainty and RR 0.09 (0.01 to 0.72), moderate certainty, respectively). No trials in older women have measured these outcomes. Vaccines reduce any CIN2(+) from 231 to 95/10,000, (RR 0.41 (0.32 to 0.52)) in younger women. No data are reported for more severe lesions. Regardless of HPV DNA status In younger women HPV vaccines reduce the risk of CIN2(+) associated with HPV16/18 from 341 to 157/10,000 (RR 0.46 (0.37 to 0.57), high certainty). Similar reductions in risk were observed for CIN3(+) associated with HPV16/18 (high certainty). The number of women with AIS associated with HPV16/18 is reduced from 14 to 5/10,000 with HPV vaccines (high certainty). HPV vaccines reduce any CIN2(+) from 559 to 391/10,000 (RR 0.70 (0.58 to 0.85, high certainty) and any AIS from 17 to 5/10,000 (RR 0.32 (0.15 to 0.67), high certainty). The reduction in any CIN3(+) differed by vaccine type (bivalent vaccine: RR 0.55 (0.43 to 0.71) and quadrivalent vaccine: RR 0.81 (0.69 to 0.96)). In women vaccinated at 24 to 45 years of age, there is moderate-certainty evidence that the risks of CIN2(+) associated with HPV16/18 and any CIN2(+) are similar between vaccinated and unvaccinated women (RR 0.74 (0.52 to 1.05) and RR 1.04 (0.83 to 1.30) respectively). No data are reported in this age group for CIN3(+) or AIS. Adverse effects The risk of serious adverse events is similar between control and HPV vaccines in women of all ages (669 versus 656/10,000, RR 0.98 (0.92 to 1.05), high certainty). Mortality was 11/10,000 in control groups compared with 14/10,000 (9 to 22) with HPV vaccine (RR 1.29 [0.85 to 1.98]; low certainty). The number of deaths was low overall but there is a higher number of deaths in older women. No pattern in the cause or timing of death has been established. Pregnancy outcomes Among those who became pregnant during the studies, we did not find an increased risk of miscarriage (1618 versus 1424/10,000, RR 0.88 (0.68 to 1.14), high certainty) or termination (931 versus 838/10,000 RR 0.90 (0.80 to 1.02), high certainty). The effects on congenital abnormalities and stillbirths are uncertain (RR 1.22 (0.88 to 1.69), moderate certainty and (RR 1.12 (0.68 to 1.83), moderate certainty, respectively). Authors' conclusions There is high-certainty evidence that HPV vaccines protect against cervical precancer in adolescent girls and young women aged 15 to 26. The effect is higher for lesions associated with HPV16/18 than for lesions irrespective of HPV type. The effect is greater in those who are negative for hrHPV or HPV16/18 DNA at enrolment than those unselected for HPV DNA status. There is moderate-certainty evidence that HPV vaccines reduce CIN2(+) in older women who are HPV16/18 negative, but not when they are unselected by HPV DNA status. We did not find an increased risk of serious adverse effects. Although the number of deaths is low overall, there were more deaths among women older than 25 years who received the vaccine. The deaths reported in the studies have been judged not to be related to the vaccine. Increased risk of adverse pregnancy outcomes after HPV vaccination cannot be excluded, although the risk of miscarriage and termination are similar between trial arms. Long-term of follow-up is needed to monitor the impact on cervical cancer, occurrence of rare harms and pregnancy outcomes