Primary HPV-based cervical cancer screening in Europe: implementation status, challenges, and future plans.

BACKGROUND: Cytology-based screening has been a cornerstone of cervical cancer prevention for decades. Following extensive evidence demonstrating higher sensitivity and accuracy, lower variability and better reproducibility of human papillomavirus (HPV)-based screening compared with conventional or liquid-based cytology, recent European guidelines strongly recommend primary HPV-based screening over standard cytology-based screening. In addition, HPV-based screening offers the possibility of self-sampling and makes possible longer screening intervals in women with negative screening results. OBJECTIVES: We summarize the current status of implementation of HPV-based screening in Europe, describe the real-life experience and challenges from countries already performing HPV-based screening, and briefly review immediate and long-term plans for screening implementation in selected European countries. SOURCES: Data were obtained from peer-reviewed literature, personal communication with experts and authorities involved in formulating national recommendations and practical guidelines, and relevant national websites. CONTENT: As of July 2019, the Netherlands and Turkey are the only European countries with fully implemented national HPV-based cervical cancer screening. Italy, Sweden and Finland have already implemented HPV-based screening in several regions, and several other countries are at various stages of implementation. Some countries are considering transitioning from cytology-based to HPV-based screening, but are struggling with the suboptimal performance of current population-based programmes. Implementation of HPV-based screening has resulted in higher colposcopy referral rates, but also higher detection rates of CIN3+ lesions and cervical cancers requiring immediate treatment. Cytology is mostly used as a triage test, although other strategies are under consideration in some countries. IMPLICATIONS: HPV-based screening is best suited in organized population-based screening settings. In 2019, cervical cancer screening policies across Europe vary greatly. Experience in countries with national and regional HPV-based screening already implemented is generally very positive. Urgent action is needed in many European countries, especially those with suboptimal opportunistic cytology-based cervical cancer screening.

Personal life and working conditions of trainees and young specialists in clinical microbiology and infectious diseases in Europe: a questionnaire survey.

The purpose of this investigation was to assess the balance between the personal and professional lives of trainees and young European specialists in clinical microbiology (CM) and infectious diseases (ID), and determine differences according to gender, country of training, workplace and specialty. The Steering Committee of the Trainee Association of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) devised a questionnaire survey consisting, beyond the demographic questions, of nine yes/no questions, 11 Likert scale self-evaluations and one open-response item on parenthood, working conditions, quality of life, alcohol consumption and burnout. This anonymous survey in English was held between April and July 2015 among European CM/ID trainees and young specialists (<3 years after training completion). Responses from 416 participants with a mean age of 32 years [standard deviation (SD) 5 years] were analysed. Females and physicians from Northern/Western Europe (NWE) benefit more from paternity/maternity leaves even during training than their counterparts. Among all respondents, only half of breastfeeding mothers enjoyed the benefit of working hours flexibility. Only two-thirds of respondents found their working environment stimulating. In comparison to colleagues from other parts of Europe, trainees and young specialists from Southern/Eastern Europe (SEE) had less frequent regular meetings with mentors/supervisors and head of departments where trainees' issues are discussed. Also, physicians from SEE were more frequently victims of workplace mobbing/bullying in comparison to those from other regions. Finally, multivariate analysis showed that female gender, SEE region and ID specialty were associated with burnout feelings. Female gender and country of work from SEE largely determine satisfactory working conditions, the possibility of parenthood leaves, amount of leisure time, mobbing experiences and burnout feelings among European CM/ID trainees and young specialists.

A large survey among European trainees in clinical microbiology and infectious disease on training systems and training adequacy: identifying the gaps and suggesting improvements.

The purpose of this investigation was to perform a survey among European clinical microbiology (CM) and infectious disease (ID) trainees on training satisfaction, training tools, and competency assessment. An online, anonymous survey in the English language was carried out between April and July 2015. There were 25 questions: seven in a 5-point Likert scale (1: worst scenario, 5: best scenario) and the remainder as closed multiple-choice questions in five areas (satisfaction, adequacy, system, mentorship, and evaluation of training). Included were 419 respondents (215 CM, 159 ID, and 45 combined CM/ID) from 31 European countries [mean age (standard deviation) 32.4 (5.3) years, 65.9 % women]. Regarding satisfaction on the training scheme, CM and ID scored 3.6 (0.9) and 3.2 (1.0), respectively. These scores varied between countries, ranging from 2.5 (1.0) for Italian ID to 4.3 (0.8) for Danish CM trainees. The majority of respondents considered training in management and health economics inadequate and e-learning and continuing medical education programs insufficient. Many trainees (65.3 % of CM and 62.9 % of ID) would like to have more opportunities to spend a part of their training abroad and expected their mentor to be more involved in helping with future career plans (63.5 % of CM and 53.4 % of ID) and practical skills (53.0 % of CM and 61.2 % of ID). Two-thirds of the respondents across the specialties agreed that a European exam should be developed, but half of them thought it should not be made mandatory. This survey shows high heterogeneity in training conditions in European countries, identifies perceived gaps in training, and suggests areas for improvements.

Immunotherapy of metastatic kidney cancer.

From April 1986 to September 2000, 122 MRCC patients were treated by monthly intralymphatic injections (containing a mean of 573 IL-2 U and 26 x 10(6) LAK cells) and i.m. administration of IFN and TF; 71 patients also received a 3-day cycle of monthly IL-2 inhalations with a mean of 998 daily U. MRCC cases not treated by immunotherapy (n = 89) represent our historical controls. Adverse clinical side effects related to treatment were negligible. CR (n = 11) and PR (n = 13) were noticed in 24/122 patients. Of 24 responding patients, 17 resumed progression, whereas 7 remain in remission 11-69 months later. The overall median survival of treated patients (28 months) was 3.5-fold higher than the median survival of historical controls (7.5 months), and a Kaplan-Meier curve showed 25% survival 11 years after the beginning of immunotherapy. Apparently, the addition of IL-2 by inhalation improved survival. The present immunotherapy protocol appears to be efficacious, safe, devoid of adverse side effects, far less costly than others and able to offer a good quality of life to MRCC patients; if confirmed in a multicenter trial, it could set the basis for developing low-dose immunomodulatory treatments.

A new regimen of cisplatin, epirubicin and methotrexate (PEM-3) as primary chemotherapy for locally advanced bladder cancer.

In this phase II study, 41 patients with locally advanced urothelial bladder cancer (T2-4, N0, M0) were treated with primary chemotherapy (cisplatin, epirubicin, methotrexate: PEM-3). All the patients were assessable for response and toxicity. Clinical monitoring was performed with computerized tomography and cystoscopy. Nineteen clinical complete remissions (46%) and 10 partial remissions (24.5%) were obtained (CR + PR, 70.5%; 95% confidence interval, 57%-85%). Ten patients were considered to have clinically stable disease (24.5%), and 2 patients progressed (5%). Surgery after chemotherapy was performed in 22 cases: in 6 patients (27%) a pathologic complete response was achieved. The pathologic stage was lower than the initial clinical stage in 13 patients (59%). After a median follow-up of 3 years (range, 1-4), the median time to progression was 104 weeks. At this writing, 20 patients, 12 of which were submitted to surgery and 8 were not operated, are disease-free. The 3-year survival rate is 52%. No one had to interrupt the treatment because of toxicity. In conclusion, the PEM-3 regimen is a very active and well-tolerated regimen in locally advanced bladder cancer.

A preliminary report on the use of transfer factor for treating stage D3 hormone-unresponsive metastatic prostate cancer.

As conventional treatments are unsuccessful, the survival rate of stage D3 prostate cancer patients is poor. Reports have suggested the existence of humoral and cell-mediated immunity (CMI) against prostate cancer tumour-associated antigens (TAA). These observations prompted us to treat stage D3 prostate cancer patients with an in vitro produced transfer factor (TF) able to transfer, in vitro and in vivo, CMI against bladder and prostate TAA. Fifty patients entered this study and received one intramuscular injection of 2-5 units of specific TF monthly. Follow-up, ranging from 1 to 9 years, showed that complete remission was achieved in 2 patients, partial remission in 6, and no progression of metastatic disease in 14. The median survival was 126 weeks, higher than the survival rates reported in the literature for patients of the same stage.

Use of transfer factor for the treatment of recurrent non-bacterial female cystitis (NBRC): a preliminary report.

Results of conventional treatment of female non-bacterial recurrent cystitis (NBRC) are discouraging. Most patients show an unexpected high incidence of vaginal candidiasis, while their cell mediated immunity to Herpes simplex viruses (HSV) and Candida antigens seems impaired, and it is known that the persistence of mucocutaneous chronic candidiasis is mainly due to a selective defect of CMI to Candida antigens. Twenty nine women suffering of NBRC, and in whom previous treatment with antibiotics and non-steroid anti-inflammatory drugs was unsuccessful, underwent oral transfer factor (TF) therapy. TF specific to Candida and/or to HSV was administered bi-weekly for the first 2 weeks, and then once a week for the following 6 months. No side effects were observed during treatment. The total observation period of our cohort was 24379 days with 353 episodes of cystitis recorded and a cumulative relapse index (RI) of 43. The observation period during and after treatment was 13920 days with 108 relapses and a cumulative RI of 23 (P < 0.0001). It, thus, seems that specific TF may be capable of controlling NBRC and alleviate the symptoms.

A 5-year profile of the incidence of total joint replacement in South Africa (1985-1989).

This survey was conducted to determine the number of total joint replacements (TJRs) carried out annually in South Africa from 1985 to 1989 and the number of surgeons performing these procedures. During this period there was a 28% increase in the number of TJRs performed annually with an average increase of 20% in total hip replacements and 40% in total knee replacements. The number of surgeons involved in joint replacement during the survey period decreased by 7% in state-subsidised institutions but increased by 57% in the private sector. This is reflected in the number of TJRs performed each year, which has remained static in the state institutions but exhibits a threefold increase in the private sector. This probably reflects a shift in emphasis in state health care policy.

Chemotherapy with cisplatin, epirubicin, methotrexate in the treatment of locally advanced or metastatic transitional cell cancer of the bladder (TCC).

Forty patients with advanced transitional cell cancer (TCC) of the bladder were treated with cisplatin, epirubicin, methotrexate (PEM, every 3-4 weeks). If creatinine clearance was reduced to 40 ml/min, the usual full doses of cisplatin and methotrexate, 50 mg/m2, were proportionally reduced. 23 patients had full-dose (FD) therapy, 17 had reduced dose (RD) (40-20 mg/m2). Two patients achieved complete response and 17 partial response. The overall response rate was 19/40 (47.5%), 11/23 (48%) for FD and 8/17 (47%) for RD (p = 1.000). 17/40 pts (42.5%) had no-change and 4/40 (10%) had disease progression. The median duration of CR and PR was 32 weeks, range 4-82 (22 weeks, range 12-52 for FD; 32 weeks, range 4-82 for RD, cisplatin p = .7362). The main side effect was vomiting (35/40 pts, 87.5%, 20/23 = 87% for FD, 15/17 = 90% for RD, p = 1.000). Leukopenia was observed in 12 patients (30%, nadir 3,240 range 900-3,800, 6/23 = 26% for FD, 6/17 = 35% for RD, p = .7285), alopecia in 18 patients (45%, 15/23 = 65% for FD, 3/17 = 18% for RD, p = .004). The results of this study show that a dose escalation to 50 mg/m2 for cisplatin, epirubicin and methotrexate in the PEM regimen results in an increase in overall response (OR) (19/40 = 47.5%) with respect to a historical control using the same drugs at doses of 40 mg/m2 (12/35 = 34%). In patients with normal renal function the escalated dose was tolerated without a corresponding increase in toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Low dose intermittent 5-fluorouracil, epirubicin and cyclophosphamide (FEC) in poor risk patients with advanced transitional cell bladder cancer: a pilot study.

Fifteen patients with locally advanced or metastatic bladder carcinoma and with cardiac and/or renal impairment were treated with a combination of 5-fluorouracil, 400 mg/m2, epirubicin, 40 mg/m2, and cyclophosphamide, 400 mg/m2. No complete or partial remissions were observed among the 14 evaluable patients. The toxicity level was very low. We are now trying to "tailor" platinum-based combinations to renal function.

Spontaneous circadian fluctuations of prostate specific antigen and prostatic acid phosphatase serum activities in patients with prostatic cancer.

Spontaneous circadian variations of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP), determined simultaneously by radioimmunoassay (RIA), were investigated by multiple sampling, over a 24-hour period, in 32 patients with prostatic cancer. In 29/32 patients (91%), the coefficient of variation of 24-hour values, for either marker, was greater than that of the RIA method at the same range of values; stage D patients showed the greatest spontaneous variability. Fluctuations around the mean of 24-hour values ranged from -65% to +85% for PAP, from -72% to +190% for PSA, occurring random and independently for each marker. Variability was about 20% greater for PSA than for PAP. The existence of spontaneous fluctuations should be considered in multiple marker evaluation of prostatic cancer patients.