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Mathilde E Boon

Publications and source records attributed to Mathilde E Boon.

At least 19 recordsLinked to original sources

Alternating high-risk human papillomavirus infection: consequences of progression to cervical intraepithelial neoplasia.

BACKGROUND: Nearly every Dutch woman will be exposed to genital human papillomavirus (HPV) at least once during her lifetime, and most likely several times. In the current study, the authors investigated the prevalence of high-risk-HPV (HR-HPV) infection and the likelihood of progression to cervical intraepithelial neoplasia (CIN). METHODS: In this study, the course of HR-HPV infection in 703 women was observed. From a database of 720,016 negative cytology smears, the authors selected 703 women based on the availability of at least 2 HR-HPV polymerase chain reaction tests. The authors database stores not only the HPV data but also all other cytologic and histologic data, allowing the detection of women who progressed from negative cytology to CIN within a period of 10 years. RESULTS: Of the 703 selected women, 159 were found to have alternating HR-HPV infection (change from a negative HR-HPV test to a positive test or vice versa), 40 had a persistently positive HR-HPV test, and 504 women had a persistently negative HR-HPV test. The percentage of alternating HPV infection declined over time from 37% to 7%. Of the women age older than 40 years, 17% had an alternating HR-HPV infection, 2 of whom developed CIN. These findings led the authors to conclude that all the women in the current study with an increased risk of developing type 2 or 3 CIN were identified using 2 HPV tests. Women age older than 40 years still have a significant risk of acquiring a HR-HPV. CONCLUSIONS: In light of the current study findings, the authors believe it is worth considering the inclusion of women age 40 years and older who have negative cytology for HPV testing as part of the Dutch national screening program.

Adult↗

Quantitative cytology on bladder wash versus voided urine: a comparison of results.

OBJECTIVES: Quantitative cytology (Quanticyt) is a valuable marker for the identification of high-risk superficial bladder cancer (SBC) patients and can be used to individualize surveillance of patients. A disadvantage is the necessity to perform an invasive procedure to obtain the required bladder wash sample. This study investigated whether quantitative cytology can be performed on voided urine with reliable results, consistent with the quantitative cytology performed on bladder wash samples. METHODS: Between June 2003 and May 2005, 288 voided urine samples in combination with bladder wash samples were obtained from patients with SBC who visited our urologic outpatient department. Quantitative cytology was performed on all samples. Corresponding clinical pathologic features and washed cytopathology results were collected. Linear regression analyses were performed for comparison of results from both types of samples. RESULTS: Ninety-one percent of the samples fell into the low or intermediate region on bladder wash. A clear deviation in the nuclear shape (MPASS) was seen in the voided urine samples, which led to more low-risk results. The clinical characteristics show that this shift is not the result of under-staging. The nuclear content (2c deviation index [DI]) did not change by performing the analysis on urine. CONCLUSION: When urine is correctly processed after voiding, quantitative cytology can be done on these samples. Voided urine-based quantitative cytology can be implemented in daily practice.

Adult↗

Dysbacteriosis in silver-stained cervical smears of Dutch-Moroccan immigrants: HPV infection and preneoplasia.

The vaginal/cervical smears of a group of Moroccan immigrants were used to compare vaginal dysbacteriosis (i.e., a bacterial population change with a decrease in lactobacilli and an increase of coccoid bacteria in vaginal/cervical smears) with Dutch women. From our archives, 779 smears from Moroccan immigrants were compared with 1,060 smears of age-matched Dutch women. For bacterial flora, Jones-Marres silver stains were used to define four groups. Koilocytosis and cervical intraepithelial neoplasia (CIN) were also recorded. The bacterial vaginal flora of Moroccan immigrants and Dutch women was different. The Moroccan women had a lower dysbacteriosis than Dutch women (3% vs. 24%). Koilocytosis and CIN were less frequent in the immigrant population. The possible synergy of a disturbed vaginal flora with human papillomavirus (HPV), HIV, or cervical preneoplasia indicates that vaginal hygiene and a normal flora may have positive effects on the uterine cervix.

Case-Control Studies↗

Dysbacteriosis and squamous (pre)neoplasia of immigrants and Dutch women as established in population-based cervical screening.

We examined the statistical relationships between dysbacteriosis and (pre)neoplasia related to age and ethnicity from the cervical screening of almost half a million smears. Data from 445,080 smears were coded according to KOPAC (the Dutch national cervical smear coding system) with nine grades. Prevalence per 100,000 smears and relative risks (RR) were calculated for dysbacteriosis and for squamous abnormalities. Patients were stratified by their probable country of origin. Dutch women had an RR of 0.92 for dysbacteriosis. Surinamese women had the highest RR for dysbacteriosis (RR = 2.36) and Moroccan women had the lowest (RR = 1.00). The same trends were seen for the risks of squamous abnormalities. The data for Turkish women follow the patterns of those for Surinamese women. The RR of dysbacteriosis is highest at 50 yr (1.28) and lowest at 35 yr (0.86). When dysbacteriotic and non-dysbacteriotic smears were compared, dysbacteriosis was observed more frequently in smears with squamous abnormalities (4.1% vs. 2.2%). Dysbacteriosis may warrant more intensive cytological surveillance and changes in lifestyle.

Adult↗

Dutch solutions for liquid-based cytology: analysis of unsatisfactory slides and HPV testing of equivocal cytology.

The liquid-based techniques to obtain microscopy slides for cervical screening have replaced conventional smears almost completely in the USA, but not in all European countries. The decision making process to use liquid-based cytology (LBC) for nationwide screening programs depends on the health system. In a pilot study of over 7,000 screenees, we analyzed the unsatisfactory LBC slides and tested the equivocal cytologies for HPV by using the LiPA test. For comparison over 48,000 conventional screening data were used. Compared to conventional smears, the LBC slides were highly cellular, the state of fixation was much better, and obscuring blood did not exist. The unsatisfactory rate showed an increase from 262/100,000 (conventional smears) to 357/100,000 (LBC slides) due to too thick, undiagnosable epithelial fragments on the LBC slides. HPV testing of the equivocal cytology leads to a better patient management and less unnecessary referrals.

Adult↗

Microscopic diagnosis of dysbacteriosis in stained vaginal smears in clinical practice.

Dysbacteriosis is a microscopical diagnosis. In women with dysbacteriosis, an overgrowth of coccoid bacteria and almost a complete absence of lactobacilli are observed in the (stained) vaginal smear. The aim of this study was to determine the accuracy of this microscopic diagnosis in clinical practice. The analysis concerned 342 consecutive cases in which the microscopy of the stained smears was performed by general practitioners trained in diagnosing dysbacteriosis. These smears were sent to the pathologist for confirmation of the microscopical diagnosis of the clinician. The cytological diagnoses of the pathologist, sometimes performed on restained slides when the quality of the staining was substandard, were considered as the "gold standard." In 92 of the 342 cases, dysbacteriosis was unequivocally established by the pathologist. Sensitivity and specificity of the microscopical diagnoses of the clinicians were 40% and 85%, respectively. There were 37 false-positive and 54 false-negative diagnoses of dysbacteriosis rendered by the clinicians. The most frequent reason for a false-negative diagnosis was an excess of lactobacilli in the smear. This study shows that even in stained smears it is difficult for clinicians to render a correct evaluation of the status of the vaginal flora.

Adult↗

Optimized quality of histologic images allows the use of neural network scanning in diagnosis of fungal infection of abnormal nails.

OBJECTIVE: The neural network scanning (NNS) system, formerly known as Papnet, is capable of selecting fungi in cervical smears. The objective of this study was to investigate whether the optimized quality of histologic images created using a combination of coagulant fixation and microwave histoprocessing allows the application of this computer-assisted microscopy in the diagnostic process. STUDY DESIGN: In a prospective study, 117 abnormal nails clinically suspect for fungal disease werefixed in a coagulant fixative, BoonFix, processed in a microwave histoprocessor to obtain optimal paraffin sections and stained with the periodic acid-Schiff (PAS) method. The stained paraffin sections were randomly numbered and screened by two independent pathologists for diagnosis of fungal hyphae and spores. The same sections were subsequently scanned by a neural network, and a maximum of 128 digital images produced by the system were screened and diagnosed by pathologists. Using light microscopy as the gold standard for diagnosis of fungi, the usefulness of NNS was then assessed. RESULTS: The fungi and spores were clearly demonstrated in the paraffin sections, and the NNS system detected and recorded them efficiently. The hyphae and spores could be identified in these pixilated images with relative ease. Of the 117 examined cases, 50 were positive and 47 negative by both methods. In the 20 remaining cases, NNS did not present images of fungi that were present in the histologic sections. In practice, this implies that only 67 out of 117 cases (57%) must be screened by light microscopy. NNS recorded not only fungi and spores in the 128 digital images but also artifacts, such as round, deeply PAS-positive granules of talcum powder, which by light microscopy might be mistaken for fungal spores. CONCLUSION: NNS proves applicable for the selection of spores and fungi if the histologic sections are of sufficiently high quality. As a result, the number of slides to be screened by light microscopy can be reduced substantially. In a throughput diagnostic laboratory handling a large number of such cases this technology can be highly valuable.

Adolescent↗

Sun exposure, sexual behavior and uterine cervical human papilloma virus.

We have previously observed marked seasonal fluctuations in the frequency of cervical smears positive for human papilloma virus (HPV) in a series of smears obtained in Holland, with a peak in the summer months, especially August. Here, we tested two possible mechanisms that might underlie this summer peak: (1) enhanced transmission of HPV due to increased seasonal sexual activity, or (2) suppression of immunity due to summertime population exposure to solar ultraviolet (UV) radiation. Data derived from a continuous series of >900,000 independent cervical smears obtained from 1983 to 1998 were assessed for histopathologic epithelial changes pathognomonic of HPV. The rate of HPV positivity was then compared to both the rate of sexual activity (using conception frequency as a readily available surrogate) as well as yearly and monthly fluctuations in solar-UV fluency. The rate of HPV positivity was found to be twice as high during the summer months, with a peak in August corresponding with maximal UV fluency. Furthermore, over these 16 consecutive years of continuous observation, maximum HPV detection rate and maximum UV fluency are positively correlated (r=0.59, P<0.01); the sunnier the year, the greater the rate of HPV. Likewise, there is a positive correlation of the monthly UV fluency, and monthly HPV discovery rate (r=0.16, P<0.03). In contrast, conception frequency (and, presumably, population sexual HPV transmission) was maximal near the vernal equinox, with relatively modest (<10%) seasonal fluctuation, i.e., not fully explaining this prominent August peak in HPV discovery. There is a clear relationship between the detection of HPV-positive cervical smears and sunlight exposure. We speculate that the well-known phenomenon of UV-mediated suppression of immune surveillance may be causally related to this unusual increase in cytologically defined active HPV infections during the summer months in northern countries such as Holland. Confirming this relationship elsewhere may be important, because whatever the risk conferred by sunlight is, in principle, behaviorally avoidable.

Adult↗

Human papillomavirus testing as a cytology gold standard: comparing Surinam with the Netherlands.

Polymerase chain reaction to detect high-risk human papillomavirus has been suggested as a gold standard for cytology. The Netherlands and Surinam were prospectively compared in regard to the proportions of Negative, Atypical Squamous Cells of Undetermined Significance, and Squamous Intraepithelial Lesion smears that had detectable high-risk human papillomavirus. For the Netherlands, 14 600 negative, 270 Atypical Squamous Cells of Undetermined Significance and 120 Squamous Intraepithelial Lesion smears were evaluated by polymerase chain reaction. For Surinam, 150 negative, 50 Atypical Squamous Cells of Undetermined Significance, and 150 Squamous Intraepithelial Lesion smears were evaluated by polymerase chain reaction. In all, 4% of Dutch and 80% of Surinamese negative smears had detectable high-risk human papillomavirus (chi2=1313, P<0.00001). In total, 41.9% of Dutch and 84% of Surinamese Atypical Squamous Cells of Undetermined Significance smears had detectable high-risk human papillomavirus (chi2=28, P<0.00001). Totally, 67.5% of Dutch and 94% of Surinamese SIL smears had detectable high-risk human papillomavirus (chi2=30, P<0.00001). The Negative: Atypical Squamous Cells of Undetermined Significance odds ratio was 0.058 for the Netherlands and 0.762 for Surinam (chi2homog=31, P<0.00001). The Negative: Squamous Intraepithelial Lesion odds ratio was 0.020 for the Netherlands and 0.255 for Surinam (chi2homog=31, P<0.00001). The Atypical Squamous Cells of Undetermined Significance: Squamous Intraepithelial Lesion odds ratio was 0.347 for the Netherlands and 0.335 for Surinam (chi2homog=0.005, P>0.75). Human papillomavirus DNA testing may not be a suitable gold standard in general because its use would make specificity and sensitivity prevalence-dependent. A new statistic, the percent of Negative pap smears with detectable high-risk human papillomavirus, is posited, which may be important if human papillomavirus DNA testing is used clinically.

Cervix Uteri↗

Season, sun, sex, and cervical cancer.

INTRODUCTION: Sunlight's UV B component, a known cellular immunosupressant, carcinogen, and activator of viral infections, is generally seasonally available. Venereal human papillomavirus (HPV) transmission, at least in part, causes cervical cancer. We have previously inspected the monthly rates of venereal HPV infection and sunlight fluency in Southern Holland over 16 consecutive years. Both peak in August with at least 2-fold seasonality. The amount of available sunlight and the rate of Papanicolaou (Pap) smear screen-detected HPV are positively correlated. We now investigate whether premalignant and malignant cervical epithelial changes are also seasonal and related to seasonal sunlight fluency. METHODS: We have studied >900,000 consecutive, serially independent, interpretable screening Pap smears obtained by a single cervical cancer screening laboratory in Leiden, Holland, during a continuous 16-year span from 1983 through 1998. The average monthly rates of premalignant and malignant epithelial change were inspected and the annual patterns contrasted to the annual pattern of sunlight fluency at this global location and to monthly average HPV infection rate. Because HPV is venereally transmitted, Dutch seasonal sexual behavior was evaluated by assessment of the annual pattern of Dutch conception frequency as a competing cause for cervical cancer seasonality. RESULTS: (a) Twice as many premalignant and malignant epithelial changes were found among Pap smears obtained in the summer months, with an August peak concurrent with histopathologic evidence of HPV infection and sunlight fluency in Southern Holland. (b) Monthly sunlight fluency is correlated positively with both the monthly rates of Pap smear-detected cervical epithelial dysplasia and carcinomatous histopathology, as well as HPV. (c) Conception frequency, in this location, peaks in Spring not summer, and has a 4.8% annual amplitude. CONCLUSIONS: (a) Cervical epithelial HPV infection and HPV-induced cervical epithelial dysplasia and carcinomatous change may each be novel sun exposure risks and thereby behaviorably avoidable. (b) Because screening Pap smears uncover many abnormalities that resolve spontaneously (false positives), these data may argue for screening and follow-up Pap smear examinations in seasons other than summer in the Northern Hemisphere, to diminish the false-positive smear rate. Global data are available to confirm and further test each of these conclusions.

Adult↗

POBASCAM, a population-based randomized controlled trial for implementation of high-risk HPV testing in cervical screening: design, methods and baseline data of 44,102 women.

Cytological cervical screening is rather inefficient because of relatively high proportions of false negative and false positive smears. To evaluate the efficiency of high-risk human papillomavirus (hrHPV) testing, by GP5+/6+ PCR-enzyme immunoassay (EIA), in conjunction with cytology (Intervention Group) to that of the classical cytology (Control Group), we initiated the Population Based Screening Study Amsterdam (POBASCAM). POBASCAM is a population-based randomized controlled trial for implementation of hrHPV testing in cervical screening. The outcome measure is the proportion of histologically confirmed > or =CIN3 lesions in each study arm up to and including the next screening round after 5 years. We present the design, methods and baseline data of POBASCAM. When, in the next 5 years, the follow-up will be completed, the data obtained will be used in model studies, including a cost-effectiveness study, to advise the Dutch Ministry of Public Health in deciding whether cervical screening should be based on combined hrHPV and cytology testing instead of cytology alone. Between January 1999 and September 2002, 44,102 women (mean age = 42.8 years; range = 29-61) that participated in the regular Dutch screening program were included in our study. In the Intervention Group the distribution of cytology and hrHPV by cytology class was as follows: normal cytology 96.6% (3.6% hrHPV positive); borderline and mild dyskaryosis (BMD) 2.5% (34.6% hrHPV positive); and moderate dyskaryosis or worse (>BMD) 0.8% (88.3% hrHPV positive), i.e., 0.4% moderate dyskaryosis (82.9% hrHPV positive), 0.3% severe dyskaryosis (92.5% hrHPV positive), 0.1% carcinoma in situ (95.2% hrHPV positive), <0.1% suspected for invasive cancer (hrHPV positive 100.0%). In the Control Group 96.5% of the women had normal cytology, 2.4% BMD and 0.8% >BMD, i.e., 0.4% moderate dyskaryosis, 0.3% severe dyskaryosis, 0.1% carcinoma in situ, <0.1% suspected for invasive cancer. The presence of hrHPV was age-dependent, decreasing from 12.0% at 29-33 years to 2.4% at 59-61 years. Among women with a positive hrHPV test, the prevalence of BMD was age-dependent ranging from 20.2% at 29-33 years to 7.8% at 54-58 years. In contrast, the risk of >BMD of 13.7% among women with a positive hrHPV test was not age-dependent. Our study indicates that large-scale hrHPV testing by GP5+/6+ PCR-EIA in the setting of population-based cervical screening is practically feasible, is accepted by both participating women and general practitioners and yields highly reproducible results.

Adult↗

Proliferation patterns of cervical cells as visualized in Leiden liquid cytology slides.

The Leiden liquid-based cytology method for the preparation of optimal cytological slides is reported. In such slides, the proliferation pattern of cervical cells can be visualized in detail. Cervical smears and suspension preparations of 665 consecutive unselected patients received in 2003 were studied. Of the 665 patients, 26 (10 normal, 10 with cervical atrophy, 5 with mild dysplasia, and 1 carcinoma in situ) were selected. After using the Thermo Shandon Papspin, the wet slides were placed on a hot plate and dried for 30 min. Proliferation of the cervical cells was visualized in brown by staining the cells for MiB-1 antigen, and nuclear DNA in blue by a standardized short staining with hematoxylin. We found excellent high-resolution demonstrability of cell cycle-related MiB-1 distribution in the well-flattened nuclei. The phase of the cell cycle could be deduced from brown-blue staining patterns. There was a significant increase of MiB-1-positive cell yield related to progression in the degree of pathology.

Carcinoma in Situ↗

Significance of MiB-1 staining in smears with atypical glandular cells.

MiB-1 immunostaining may facilitate recognition of developing adenocarcinoma in cervical smear screening. In a retrospective analysis of prospectively collected data of 170 patients with atypical endocervical glandular cells and with repeat smears, archival Papanicolaou-stained smears were restained for MiB-1 and classified for the presence of preneoplastic changes of MiB-1 positive epithelial fragments. The results of classification based on MiB-1 positive epithelial fragments corresponded "roughly" with cytomorphological diagnoses. Of the 38 patients in which the primary smear was found to be MiB-1-positive, 12 of these persisted in the repeat smear. Thirty-eight of the 132 repeat smears of patients originally negative for MiB-1 pathology were positive. Of the total 50 MiB-1 positive repeat smears, four showed adenocarcinoma in situ on cytomorphological grounds. MiB-1 staining enhances detection of (pre)neoplastic changes. This approach does not destroy the morphology of the original smear and can be applied to routine material.

Biomarkers, Tumor↗

Using urbanization profiles to assess screening performance.

The large Dutch data sets acquired as a result of population-based cervical smear screening programs can be further exploited to obtain an urbanization-weighted score to gain insight into the quality of the performance of the individual cytology laboratories. Based on the first four digits of the postal code of the screenees, the data are stratified according to urbanization. Urb 1 corresponds to (semi)rural, which includes villages and small townships with less than 20,000 inhabitants; Urb 2, to towns with between 20,000 and 250,000 inhabitants; and Urb 3, to big cities, in this case, The Hague. From the postal code data of the screenees, the urbanization profiles of the laboratories can be calculated. The urbanization degree proved to have a substantial effect on the cytologic scores in the four laboratories. The number of expected, urbanization-weighted patient cases is calculated. Accordingly, the laboratories could be compared with respect to performance. We conclude that laboratories in our screening program were quite similar in performance for the cytologic diagnosis leading to referral to the hospital, with little difference between the actual and the expected, urbanization-weighted number of cases. It is evident that the equation for calculating the expected scores for S5-S9 is relevant for control of quality of care provided by laboratories and regions, but also for the quality of these assessments.

Female↗

Proliferation patterns reflect architectural dedifferentiation: a study of nodular basal cell carcinoma.

The distribution of proliferating cells in basal cell carcinoma (BCC) may be related to lesion type and architecture. Single proliferation indexes may not be representative. We aimed to establish the distribution of cell proliferation in BCC as related to architecture. We studied an unselected, consecutive series of 45 resection specimens of nodular BCC from patients in the age range of 25-95 years using MIB-1 staining and systematically reviewed the cases. These lesions included nodular (n=32) and non-nodular (n=9) BCC. Within the nodular BCC, two patterns were recognised, not related to age or gender. In small nodular patterns with well developed peripheral palisading and central parallel streaming of small, elongated nuclei, proliferation is limited to the basal palisading cells in a clustered distribution. In large nodular patterns, proliferation is absent at the basal membrane (BM) and distributed in single random cells throughout the lesion. Both patterns preclude accurate quantitation. Many lesions contained both patterns in a side-by-side, unmixed manner. These pattern differences suggest a loss of differentiation in nodular BCC. Perhaps a single mutation results in the loss of BM associated cell architecture and proliferation control related to tumor-stroma interactions. As a result, the lesion reverts to a low frequency, non-regulated proliferation, diffusely distributed throughout the lesion. The two patterns may exist side-by-side in a single lesion, further supporting the concept of polyclonality. This hypothesis explains perilesional clefting and previously reported variations in intra-lesional laminin synthesis. Based on our findings, representation of tumor cell proliferation activity by a single value is not justified. Nodular BCC exists in one of two dedifferentiation-mutation-determined patterns of cell proliferation; many lesions clearly demonstrate bi-clonality.

Adult↗

Urbanization and the incidence of abnormalities of squamous and glandular epithelium of the cervix.

BACKGROUND: The large data bases of the Dutch cervical screening program can be exploited to establish the relation between urbanization and the incidence of abnormalities of the squamous and glandular epithelium, including mild or greater changes of the squamous and glandular epithelium of the cervix. METHODS: Six cytology laboratories in the context of the Dutch cervical screening program screened over 190,000 cervical smears. Urbanization (place of residence) data were derived from postal codes. All smears were coded with the Dutch national coding system, the Dutch national classification system KOPAC, in which squamous abnormalities are coded S4-S9, and glandular cell changes are coded G4-G9. From the scores per 1000 screened women, the relative risk (RR) of living in a large city compared with living in rural areas was calculated. To investigate a trend in incidence in relation to urbanization, the Schaafsma method was used. RESULTS: Of the smears with positive cytology, mild squamous dysplasia (S4) had the highest incidence per 1000 screened women (4.32), and the lowest incidence was found for adenocarcinoma (in situ; G7/G9; RR, 0.07). The RR for urban women ranged from 1.73 for moderate squamous dysplasia (S5) to 7.55 for adenocarcinoma (in situ; G7/G9). For smears with positive cytology for both squamous and glandular abnormalities, the Schaafsma method indicated a significant positive trend. CONCLUSIONS: The incidence of squamous and glandular abnormalities are maximal in women who live in a large city, which, in The Netherlands, is where there also is a population at high risk for human papillomavirus and bacterial vaginosis.

Adenocarcinoma↗

Clinical and diagnostic significance of blood in cervical smears.

A heavy admixture of blood in cervical smears can be problematic for the screener, as the presence of blood can influence the staining quality of the cancer cell nuclei. However, it might also be a blessing in disguise. A retrospective study of 40 clinically important smears, 34 originally signed out as negative for squamous cell carcinoma of the cervix and 6 smears as unsatisfactory, was carried out in comparison with 100 smears from healthy women. Sample parameters were analyzed by macroscopy and neural network scanning. Differences between the two study groups were measured by Pearson's chi(2) test. Of the 40 study cases, one case featured insufficient material, while 16 cases (40%) could confidently be classified as malignant or negative for malignancy. The most important macroscopic parameter of the smears was an admixture of blood. This background feature was also highlighted by the NNS system. Angiogenesis was visualized by the expression of CD34 in many sampled capillary fragments included in the smears. In conclusion, blood in cervical smears may have clinical and diagnostic significance. The rate of "failed smears" in routine cervical screening might thus by CD34 be considerably decreased.

Antigens, CD34↗