Management of patients with two consecutive ASC-US smears.

INTRODUCTION: To determine whether aggressive or expectative management of patients after two consecutive smears with atypical squamous cells of undetermined significance is preferable. To determine whether triage with high-risk human papillomavirus will identify all patients with cervical intraepithelial neoplasia grade 2 and 3. METHODS: 140 of 282 patients referred for colposcopy with two consecutive smears with atypical squamous cells of undetermined significance were only treated when abnormalities suggestive of high-grade cervical intraepithelial neoplasia were present at colposcopy. The other 142 patients underwent excision of all detected colposcopic abnormalities. Both groups were compared regarding the final cytological follow-up, the number of diathermy loop excisions, and the detection of cervical intraepithelial neoplasia. Retrospectively, the outcome of triage with high-risk human papillomavirus in the first group was investigated. RESULTS: There was no significant difference in final cytological follow-up between patients managed by expectative or by aggressive colposcopic management. Significantly less diathermy loop excisions (p < 0.001) are performed in case of expectative management. The sensitivity, specificity, negative- and positive predictive values of triage with high-risk human papillomavirus detection were comparable with those of colposcopy alone. CONCLUSIONS: Patients referred with two consecutive ASC-US smears may be followed with an expectative colposcopic management and cytological follow-up. Triage with high-risk human papillomavirus will reduce the number of referrals and colposcopies, but (cytological) follow-up remains necessary in all high-risk human papillomavirus negative patients as well.

Prevalence of squamous abnormalities in women with a recent smear without endocervical cells is lower as compared to women with smears with endocervical cells.

The purpose of this study was to determine the prevalence rate ratio of squamous lesions in women with recent smears without endocervical component (ECC-) versus women having a smear with ECC+ and to estimate the true prevalence of these lesions in women with ECC- smears by addition of short-term follow-up results of negative ECC- smears. Results of initial smears in a 3-year period, as well as follow-up results of negative ECC- smears in the same period were retrieved. Women were categorized into two groups: having ECC- and ECC+ smears. The data were analysed for three outcome parameters, ASCUS or higher (ASCUS+), LSIL or higher (LSIL+) and HSIL or higher (HSIL+). Squamous abnormalities occurred far less frequently in women with initial ECC- than with ECC+ smears. Prevalence rate ratio (PRR) was 0.27 for ASCUS+, 0.39 for LSIL+ and 0.36 for HSIL+. Addition of follow-up results of negative ECC- smears, as a correction for false-negative ECC- smears, results in PRRs which are still significantly lower than 1, and most marked in subset HSIL+ (PRR = 0.60). We conclude that the true prevalence of squamous lesions in women with recent ECC- smears is significantly lower as compared with ECC+ smears. These findings lent support to the decision to abolish the repeat of ECC- smears in the Dutch population screening programme.

[Wait-and-see policy versus loop excision after two consecutive Pap-2 cervical smears: over time less surgery and an equivalent outcome; no substantial contribution to be expected from the detection of high risk human papillomavirus]. / Expectatief beleid versus lisexcisies na 2 opeenvolgende Pap-2-uitstrijkjes: op termijn minder ingrepen en een gelijke uitkomst; geen wezenlijke bijdrage te verwachten van detectie van hoogrisico-humaanpapillomavirus.

OBJECTIVE: To determine the number interventions and outcomes in patients referred with two consecutive Pap 2 cervical smear results who were managed either by a wait-and-see policy or aggressively, and to determine whether triage with high-risk human papillomavirus (hr-HPV) detection, resulting in the referral of only hr-HPV positive patients, would lead to the detection of all patients with cervical intraepithelial neoplasia (CIN). DESIGN: Retrospective comparison and retrospective cohort study. METHOD: 282 patients referred in 1997/'99 with 2 consecutive Pap 2 cervical smears in the screening program were included. Patients referred to the UMC St Radboud Hospital (n = 140; mean age: 45 years) underwent a colposcopy during which only lesions suggestive for CIN 3 were treated. All other colposcopic lesions (CIN 2 or less) were not treated but followed prospectively. Patients referred to the Canisius Wilhelmina Hospital (CWZ) (n = 142; mean age: 44 years) underwent colposcopy during which all colposcopic lesions (including CIN 2 or less) were treated directly. The two groups were compared in terms of the final cytological follow-up, the number of loop excisions, and the number of patients with CIN. The mean follow up was 40 months. In the first group, the effect of triage using hr-HPV detection was also investigated retrospectively. RESULTS: With the wait-and-see approach, statistically significantly fewer diathermic loop excisions were done: 13 versus 124. After the follow-up period there was no statistically significant difference between the two groups in terms of the number of patients with persisting Pap 2: 16 (11%) versus 12 (8%). Triage with hr-HPV detection would identify all patients with CIN 3, 50% of the patients with CIN 2, and none of the patients with CIN 1; of the 48 hr-HPV-positive women, 1 had a CIN 3 lesion and 3 had a CIN 2 lesion; of the remaining 92 women, 2 had a CIN 1 lesion and 3 had a CIN 2 lesion. CONCLUSION: The wait-and-see approach led to fewer interventions, while the number of women with persisting Pap 2 smears was not higher than with the aggressive approach. Triage with hr-HPV may reduce the number of referrals and colposcopies, but follow-up remains necessary in all women regardless of hr-HPV status.

The value of loop electrosurgical conization in the treatment of stage IA1 microinvasive carcinoma of the uterine cervix.

The objective of this study is to assess the value of Loop Electrosurgical Conization (LEC) in the treatment of stage IA1 microinvasive squamous cell carcinoma (MIC) of the uterine cervix. Retrospectively, 82 patients with FIGO stage IA1 MIC, primarily treated with LEC on see and treat basis, were analyzed. After the initial LEC, 16 patients received cytologic and colposcopic follow-up only, 66 patients underwent a second procedure (repeat LEC, Cold Knife Conization (CKC), or hysterectomy), and four patients underwent a third procedure (hysterectomy). In 63 patients (77%) no residual CIN 3 or MIC was present after the initial LEC. Treatment of residual CIN 3 or MIC was equally effective with a repeat LEC as with CKC. One patient defaulted follow-up and developed a recurrence in the vaginal vault and was treated with a radical hysterectomy. LEC can be used as an alternative for CKC in treatment of patients with stage IA1 MIC. The advantage of LEC is that it can be performed as an outpatient procedure in addition to a diagnostic colposcopy and does not require a major anesthetic. Only a small number of patients will need a more extensive procedure.

[A repeat advice no longer applies for cervical smears without endocervical cells in population studies for cervical cancer]. / Geen herhalingsadvies meer bij een cervixuitstrijk zonder endocervicale cellen in het bevolkingsonderzoek op baarmoederhalskanker.

Recent Dutch and non-Dutch studies have shown that the absence of endocervical cells (ecc-) in an adequate cervical smear does not present an increased risk for the presence or occurrence of cervical cancer or premalignant abnormalities in a later phase. Based on these findings, the Coordination Committee Cervical Cancer Screening of the Dutch Health Insurance Council had advised dropping the repeat advice for non-abnormal ecc- smears by January 1st 2002. The National Health Insurance Council has agreed to this advice. The following measures have been taken: (a) no repeat advice for ecc- smears; in the case of negative findings the woman waits until the next five-yearly invitation from the screening programme; (b) whether the portio cervicis was seen has to be stated on the national request form; (c) the reporting of an ecc- in the cytology report and periodical feedback to general practitioners remains unchanged; (d) in the case of a non-abnormal ecc- smear with an uninspected portio or doubts as to whether the transformation zone was adequately scraped, either the smear will have to be repeated or the patient will have to be referred to the gynaecologist.

Additional techniques in serous effusions.

Cytological examination is a valuable diagnostic tool in case of a serous effusion. The first manifestation of malignancy may be an effusion of the pleural, pericardial, or peritoneal cavity, especially in carcinoma of the ovary, or lung, and malignant mesothelioma. In other malignancies effusions may occur in the course of the disease. The contribution by Mother by et al. in this issue of ACP focuses on the contribution of image and flow cytometry to establish the presence or absence of malignancy in serous effusions. They point out that the sensitivity of DNA image cytometry in equivocal effusions may be as high as 87.5%, and that for the detection of malignancy, DNA image cytometry is superior to flow cytometry.

Fluctuations in prevalence of cervical human papillomavirus in women frequently sampled during a single menstrual cycle.

In the last few years much attention has been focused on the implementation of human papillomavirus detection in population based screening programmes to identify women at risk for cervical cancer. Short-term fluctuations in prevalence of human papillomavirus were investigated within a single menstrual cycle. The highest prevalence was found at the follicular phase (55%), whereas the cumulative prevalence was 75%.

Localized distribution of human papillomavirus genotypes in the uterine cervix.

INTRODUCTION: The localization and distribution of single or multiple HPV genotypes in the uterine cervix has not been studied thus far. The present study was undertaken to determine whether single or multiple HPV genotypes detected in cervical smears originate from a single (dysplastic) area, or from different areas (dysplastic or normal) of the uterine cervix. METHODS: Of eight patients with moderate or severe dysplasia, 31 colposcopically guided biopsies of different dysplastic lesions of the uterine cervix, as well as of normal epithelium were investigated. A highly sensitive, broad spectrum, short fragment polymerase chain reaction (SPF-10 PCR) HPV detection method in combination with a line probe assay (LiPA) for simultaneous genotyping was used. RESULTS: In the uterine cervix of four of the eight patients, multiple HPV genotypes were detected. These multiple HPV genotypes were detected in different biopsies as well as within a single biopsy. In three patients, all with carcinoma in situ or microinvasive carcinoma, only a single HPV genotype, HPV 16, was found all over the cervix including in the normal epithelium. CONCLUSION: Different HPV genotypes can be detected in different dysplastic lesions as well as within single lesions, especially in patients with severe dysplasia. The severity of the lesion may possibly have a relation with the distribution of the HPV genotypes. The low number of patients and biopsies does not allow definite conclusions. However, the impact of these findings on the outcome of screening and vaccination programs remains to be elucidated.

The effect of Replens on vaginal cytology in the treatment of postmenopausal atrophy: cytomorphology versus computerised cytometry.

BACKGROUND: After the menopause decreased concentrations of oestrogen may result in insufficient maturation of the vaginal epithelium, which can lead to a range of vaginal discomforts. This state of vaginal atrophy may be treated with oestrogen replacement treatment. Replens, a non-hormonal alternative to oestrogen replacement treatment has been shown to be effective in relieving symptoms related to vaginal atrophy in previous studies. AIMS: To study the effect of Replens on the maturation of the vaginal epithelium and morphology of the vaginal cells and to compare the results of a recently developed cytomorphometric method with manual assessment of the degree of maturation in vaginal smears. METHODS: Vaginal smears from 38 postmenopausal women suffering from symptoms related to vaginal atrophy were analysed manually and by cytomorphometry. The maturation value (MV) and the percentages of (para)basal, intermediate, and superficial cells (maturation index; MI) were measured by both methods before and after treatment with Replens. Cytomorphometry also measured mean cellular area, mean nuclear area, and mean area ratio. RESULTS: A correlation was shown between the two methods in the assessment of percentages of (para) basal and intermediate cells and MV. Cytomorphometric data showed a significant increase in mean cellular area, indicating a positive effect of Replens on the maturation of the vaginal epithelium. Changes in nuclear area and ratio between nuclear and cellular areas were not significant. Treatment with Replens did not influence MI or MV, as assessed by the two methods. CONCLUSIONS: Replens did have an effect on vaginal morphology. The automated procedure may be useful for the assessment of maturation in vaginal smears and is more sensitive to small (subvisual) changes.

alpha-Catenin expression pattern and DNA image-analysis cytometry have no additional value over primary histology in clinical stage I nonseminomatous testicular cancer.

OBJECTIVE: To determine whether the alpha-catenin expression pattern and DNA content have additional value over primary tumour histology, including information on vascular invasion and tunica albuginea invasion, in detecting occult metastasis in patients with clinical stage I nonseminomatous germ cell tumours of the testis (NSGCT). PATIENTS AND METHODS: Fifty consecutive patients with clinical stage I NSGCT underwent retroperitoneal lymphadenectomy (RPLND) between 1986 and 1992. The orchidectomy specimens were histopathologically reviewed and immunohistochemically stained with mouse monoclonal anti-alpha-catenin antibody. The presence of an aberrant or negative staining in >10% of the malignant cells was defined as abnormal; in all other cases tumours were classified as normal. Furthermore, intact nuclei were isolated from 50 microm thick paraffin sections of the primary tumour, Feulgen stained, and analysed with an image-analysis system. RESULTS: Of the 50 patients, 14 had positive retroperitoneal nodes (stage IIa, 28%), one pathologically staged I patient developed a lung metastasis (stage IV) within 3 months of RPLND. Univariate analysis showed that the presence of embryonal cell carcinoma, vascular invasion and tunica albuginea invasion were predictive for occult metastases. In multivariate logistic regression analysis only vascular and tunica albuginea invasion were significant. All 11 patients with no embryonal cell carcinoma in the primary tumour were classified as having pathological stage I disease. Also, the tumours which were DNA-diploid (three) or DNA-polyploid (two) were pathologically stage I. In screening for occult metastases the DNA content and the alpha-catenin expression pattern had no additional value. CONCLUSION: Vascular and tunica albuginea invasion have prognostic value in identifying patients with clinical stage I NSGCT at high risk for occult retroperitoneal disease. In contrast, the absence of embryonal cell carcinoma could predict all patients at low risk for metastasis. The DNA-ploidy also identified patients at low risk. Other DNA-analyses and the alpha-catenin expression pattern provided no additional information. Further studies are recommended to identify patients who are at low or high risk for metastasis.