In the past twenty years the products of Rovers Medical Devices have been tested in many different clinical trials. Below you find a collection of theses containing clinical trials in which products of Rovers Medical Devices have been used.

Roosmarie de Bie, 2011

Title thesis: Opportunities for improvement of cervical cancer prevention – from invitation to clinical care

De Bie evaluates in her thesis the weaknesses of the current cervical cancer screening program and treatment options of patients with (pre)malignancies. Furthermore, opportunities for improvement of the cervical screening program, such as self-sampling for hrHPV detection were described in this thesis.

De Bie described the screening history of women with invasive cervical cancer. Attention in the screening program must be directed towards minimizing false-negative smears. The normal smears within the preceding screening interval of five years were subsequently reviewed. A substantial part we scored as sampling and interpretation errors.

Two different treatment strategies for two consecutive ASC-US smears, aggressive versus less aggressive, were described and the clinical outcome after follow-up was compared. Both strategies were equally safe and showed good clinical outcomes.

De Bie described in her thesis the relation between HPV related vulvar cancer (u-VIN) and cervical abnormalities, and gives some suggestions for clinicians to improve uptake of HPV related malignancies.

Finally, the potential use of the FTA elute cartridge in combination with the Viba Brush to detect (pre)malignancies of cervical cancer is tested with the clinically validated Hybrid Capture 2 and GP5+/6+-HPV DNA detection assays. The FTA cartridge showed only a reasonably good overall agreement for hrHPV detection with liquid-based media when using GP5+/6+-PCR.

Read more

Murat Gök, 2012

Title thesis: HPV testing on self-collected cervico-vaginal material: a new way of woman-friendly cervical screening

Gök focussed in his thesis on the results of two large self-sampling studies that implement hrHPV testing on self-sampled (cervico)-vaginal material from non-attendees of the cervical screening programme. In PROHTECT (PRotection by Offering HPV TEsting on Cervico-vaginal specimens Trial) -1, the Delphi Screener and in PROHTECT-2, the Viba brush were offered for hrHPV testing to non-responders of the regular cervical screening programme in a large, population-based screening setting. Both studies showed that the response rate in the self-sampling group was significantly higher than in the control group that received a recall for regular cytology screening (PROHTECT-1: 27.5%, and PROHTECT-2: 30.8%; p<0.001 in both studies). The yield of CIN2+ and CIN3+ lesions in self-sampling responders were 1.3-1.5% and 1.0%, respectively.

In women with CIN2+ and CIN3+ the concordance was very high (93.8% and 95.5%, respectively). These studies indicated that offering self-sampling for hrHPV testing is a much better alternative for women not attending the screening programme than sending them a second screening reminder letter.

In a pooled analyses of both PROHTECT studies Gök evaluated attendance on ethnicity, age, and screening history. He concluded that screening history appeared the main determinant for risk of high-grade CIN and cervical cancer. These results indicate that offering self-sampling is a feasible and effective method to protect non-attendees of cervical screening, irrespective of their ethnic background, and that the highest benefit of this approach can be expected for underscreened and unscreened women.

Read more

Channa Schmeink, 2012

Title thesis: Dynamics of genital human papillomavirus in young women

Schmeink presented in her thesis work that is based on the longitudinal data of a large prospective epidemiologic study in young women in the pre-vaccine era. In this cohort the Viba Brush was used. The main objective is to focus on the incidence, clearance and persistence of HPV, and associated risk factors like age, sexual behavior, oral contraceptives and pregnancy.

Schmeink described the HPV incidence rates in young females, and whether the relation with the sexual behaviour is age-dependent. Furthermore, the clearance rate of type-specific infections and whether re-infection with the same type takes place during 12 months of follow-up was studied. Additionally, the potential factors influencing type-specific HPV clearance like age, smoking and sexual behaviour were evaluated.

Factors potentially influencing the dynamics of HPV, such as the potential influence from oral contraceptive pill use and sample timing within the menstrual cycle, and the potential influence of pregnancy on HPV detection are described in this thesis. Follow-up data were related to the results of type-specific HPV detection with available cytology results. The Cervex-Brush was used for Pap smears.

Read more

Kathleen D’Hauwers, 2013

Title thesis: HPV in men

D’Hauwers investigated in her thesis how frequently HPV occurs in combination with penile cancer in Belgium; how best to screen men for HPV; what men and women currently know about the virus, infection and cancer as a possible consequence; and their attitudes towards HPV vaccination.

D’Hauwers examined a group of men suffering from penile cancer. HPV was found to be present in the surgical tissue of 71% of these patients. This does not necessarily mean that HPV caused all of these penile cancers: the presence of HPV in combination with cancer might be coincidental. D’Hauwers tested HPV in urine, sperm and urethral smears, and concluded that the urine method is insufficiently sensitive to allow for the reliable detection of HPV. Sperm cells are perfectly suited to this kind of investigation; however, the virus is not found in the sperm of all men who have HPV. Urethral smears yield a sufficient quantity of cells and DNA material and also contain HPV, but only if the man’s partner has also tested positive for HPV. If the smear was less painful it would be an ideal screening method.

People’s increasing awareness of the need for HPV vaccination was highlighted by one of D’Hauwers’ studies. Willingness to be vaccinated against HPV was found to have increased between 2006 and 2012. Also, participants’ knowledge of HPV and its consequences were found to have increased over time.

Read more

Astrid Baalbergen, 2014

Title thesis: Adenocarcinoma of the Uterine Cervix and its Precursor Lesion

Baalbergen gives in her thesis more insight in adenocarcinoma of the uterine cervix. The more common cervix carcinoma, squamous cell carcinoma, has been thoroughly studied and published. Adenocarcinoma of the cervix used to be a rare cervical tumor, only 5% of all cervical cancers, lately its incidence has been increasing to 20%. Adenocarcinoma of the cervix was said to have a worse survival and therefore more radical therapy was adjusted. The incidence of adenocarcinoma of the cervix has not declined as the incidence of squamous cell carcinoma after starting the screening programs, which was due to the inability to detect abnormalities in glandular cells in cervical cytology.

Read more

Kim Meeuwis, 2014

Title thesis: Clinical studies on genital psoriasis and HPV-related lesions, a multidisciplinary approach

Meeuwis describes in her thesis both clinical studies on genital psoriasis and HPV-related anogenital (pre)malignancies in female renal transplant recipients (RTRs). Female renal transplant recipients have an elevated risk for HPV-related anogenital (pre)malignancies in this population, therefore additional attention to screening and prevention of these lesions is required. Specific themes that were studied in this thesis include cervical screening in female renal transplant recipients, prevalence of gynaecological (pre)malignancies in the female RTR population, clinical overview of anogenital malignancies in female RTRs and HPV genotype distribution in these lesions, epidemiology of HPV infections in female renal transplant recipients. Meeuwis used in her research the Cervex-Brush for physician-taken scrapes and the Evalyn Brush for self-sampling.

Read more

Aniek Boers, 2014

Title thesis: Innovative molecular markers for diagnosis and prognosis in cervical neoplasia

Boers described in her thesis improvements of the current cervical cancer screening program and treatment of cervical cancer patients. A wide variety of methylation markers has been explored for cervical cancer screening, but so far no methylation markers are validated for optimal detection of (pre)malignant cervical neoplasia in a population based screening program.

In a review an overview is shown of the markers known in literature and the best methylation markers for cervical cancer screening reported so far. Furthermore, Boers describes an innovative genome-wide methylation analysis to identify new methylation markers that can differentiate between normal cervices and CIN2 or higher lesions.

Detection of hrHPV in self-obtained cervico-vaginal samples is feasible, while cytological assessment of self-sampler material is not reliable. Optimizing triage of HPV positive women is necessary, because of its specificity. DNA methylation analysis with a 4-gene panel C13ORF18, JAM3, EPB41L3 and TERT as a triage test was performed directly on Evalyn Brush specimens. Boers concluded that DNA methylation is feasible directly on the Evalyn Brush and showed good correlation with matched physician-taken samples.

Apart from optimizing screening strategies for cervical cancer, possible improvements of the current standard of care of cervical cancer patients were described in this thesis. Boers studied in cervical cancer the role of ATG13-mediated autophagy in response to irradiation.

Read more

Maaike Dijkstra, 2014

Title thesis: Towards a more objective way of cervical cancer screening: cervical cancer screening 2.0

Dijkstra describes in her thesis work evaluating opportunities of hrHPV and subsequent triage testing on the way towards a more objective manner of cervical cancer screening.

In one of her studies, Dijkstra concluded that brush-based self-sampling with the Viba Brush in combination with GP5+/6+-PCR EIA hrHPV testing is acceptable to women and valid for assessing the risk of CIN2+ in comparison to hrHPV testing on regular a cervical scrape using a the Cervex-brush. In addition, there was high concordance of HPV genotyping results.

The POBASCAM trial is a large population-based screening trial in which the Cervex Brush is used for cytology. Dijkstra used in a substudy of the POBASCAM trial, a large cohort of hrHPV-positive women to evaluate different triage strategies, involving testing at baseline and six months with combinations of cytology, HPV16/18 genotyping, and/or repeat hrHPV testing. Dijkstra concluded in this study that triaging hrHPV-positive women by cytology at baseline and after 6 to 12 months, possibly in combination with baseline HPV16/18 genotyping, seems acceptable for cervical cancer screening.

In a long-term follow up study of the POBASCAM trial, published in the BMJ, Dijkstra describes that the absolute risks of CIN3+ and cancer among hrHPV screen-negatives were low, justifying an extension of the screening interval beyond the current 5-year interval in the Netherlands, in particular for women aged 40 and older. HrHPV positive, triage negative women have an elevated CIN3+ risk and should be rescreened within 5 years.

Read more

Romy van Baars, 2014

Title thesis: Improving Cervical Cancer Prevention by HPV Self-sampling, Colposcopy and Biomarkers.

Romy van Baars explored in her thesis alternative methodologies aiming at improvements at various steps of the cervical cancer screening, including sampling for primary testing, secondary (i.e. triage) testing, and diagnostic (colposcopy and pathology) work-up steps. Van Baars evaluated, for example, the clinical sensitivity and sensitivity for CIN2+ of HPV testing using a combination of the Viba brush and a solid-state sample carrier, the FTA cartridge, for dry transport of self-collected brush samples. FTA-based self-collection might be valuable when a liquid-based medium cannot be used, for example in screening of nonresponders and in low-resource settings. Van Baars concluded that the clinical performance of hrHPV detection is determined by both the sample collection system and the test method.

Subsequently van Baars investigated acceptability of the Evalyn Brush, and its suitability as a dry transport system compared to concurrently physician-obtained samples for the detection of hrHPV. She concluded that self-sampling using the dry Evalyn Brush system is as good as a physician-taken sample for hrHPV detection. Furthermore, the Evalyn Brush was a highly acceptable self-sampling device to 98% of the women in this study.

Read more

Remko Bosgraaf, 2014

Title thesis: Improving cervical cancer screening in the HPV era

Bosgraaf describes in his thesis on the results of a large self-sampling study (PROHTECT-3B: PRotection by Offering HPV TEsting on Cervico-vaginal specimens Trial). In this randomized controlled trial (PROHTECT-3B), Bosgraaf compared two novel self-sampling devices for HPV detection on such a large scale.

In this study, 30,130 eligible women were randomly assigned (1:1 ratio) to receive either a Evalyn Brush or Delphi Screener for HPV testing. Bosgraaf found that the Evalyn Brush is noninferior to the Delphi Screener in terms of participation rate, with a higher participation rate for the Evalyn Brush (34.6% vs 31.9%). The Cervex-Brush was in this study used for physician-taken triage scrapes of HPV self-sampling positive women. Moreover, similar HPV-positivity rates and CIN2+/CIN3+ rates were observed in the two groups. A questionnaire that was sent to all invitees reported a similar user comfort with both self-sampling devices.

Furthermore, Bosgraaf explored the value of hrHPV genotyping combined with cytology as triage tool for hrHPV-positive women. In both studies the Cervex-Brush was used for physician-taken triage scrapes of HPV self-sampling positive women. Bosgraaf concluded that triage by cytology testing can be improved by adjusting its threshold, and combining it with HPV16/18 genotyping. These strategies improve the referral rate and specificity for detecting CIN3+ lesions, while maintaining adequate sensitivity.

Read more

Viola Verhoef, 2014

Title thesis: Improving cervical cancer screening by HPV self-sampling

Viola Verhoef gives in her thesis more insight in the clinical accuracy and acceptability of HPV self-sampling and the improvement of cervical screening among non-attendees by offering self-sampling. Moreover, several triage strategies were evaluated in different studies in women tested HPV positive on self-sampled material.

Verhoef compared in a study the current Delphi Screener with a former generation Delphi Screener among non-responders of the screening program in the Netherlands. Verhoef showed that both devices performed similar in clinical performance and response rates.

In a large randomized controlled trial, PROHTECT-3, Verhoef compared two different triage strategies of women tested HPV positive with the Delphi Screener. Triage of HPV positive women is needed to prevent over-referral and overtreatment. Verhoef compared cytology as a triage tool with a DNA methylation of biomarker (MAL-M1 and miR-124-2) to detect CIN3+ on self-collected cervico-vaginal lavage material of women with an HPV positive self-sample. Verhoef found similar CIN2+ detection rates in the molecular triage and cytology triage group. In addition, women who received molecular triage did not need an additional visit to the physician for triage testing, showed a better compliance and shorter diagnostic track, at the cost of a higher colposcopy referral rate.

Furthermore, Verhoef combined in other studies different triage strategies of HPV positive women by, for example, cytology, DNA methylation analysis at different thresholds and/or HPV16/18 genotyping. The good performance of these different triage strategies is attractive for full molecular screening, to identify women with cervical (pre)cancer among HPV self-sample positive women.

Read more

Lise de Strooper, 2016

Title thesis: Triage of HPV-positive women by methylation marker analysis

De Strooper presents in her thesis work evaluating DNA methylation markers as candidate triage tests for hrHPV-positive women. It elaborates on methylation of the promoter regions of the tumour suppressor genes CADM1, MAL, mir124-2, and FAM19A4, which provide highly appealing disease markers for hrHPV-positive women. The studies described herein could contribute to a more objective manner of cervical cancer screening, both applicable to physician-taken scrapes and self-collected samples. De Strooper used in her research the Cervex-Brush for physician-taken scrapes and both the Delphi-screener as well as Evalyn Brush for self-sampling.

Read more

Loes van den Einden, 2016

Title thesis: Improving care for women with vulvar squamous (pre)malignancies

Loes van den Einden describes in her thesis opportunities for the further improvement of clinical care of women with vulvar (pre)malignancies with the focus on the diagnostic process and treatment. Vulvar lesions are sometimes difficult to diagnose by clinical doctors such as GPs, dermatologists, gynaecologists and pathologists because of the rarity of vulvar squamous (pre)malignancies with a variety of symptoms. Proper and timely treatment is important in order to minimise the morbidity and mortality caused by these lesions. In one of the studies presented in this thesis, the clinical use of the Vulva-Brush is described. The accuracy for (pre)malignant lesions with the use of a Vulva-Brush showed a sensitivity of 97% and a negative predictive value of 88%. Based on these results Van den Einden concluded that vulvar brush cytology is feasible and may be a first step in the development of a triage instrument to determine whether subsequent biopsy of a clinically suspicious lesion is necessary.

Read more