Comparing two modalities of management of women with cytologic evidence of squamous or glandular atypia: early repeat cytology or colposcopy

Early repeat cytology is recommended in most screening programs for cervical cancer in subjects with squamous or glandular abnormalities not amounting to neoplasia (atypical squamous cells of undetermined significance, ASCUS), but immediate colposcopy is also recommended in some countries, especially those where there is easy access to colposcopic facilities. We evaluated the cost-effectiveness of the two procedures in a prospective study of women with cytologic ASCUS, invited to cytocolposcopic assessment after 6 months. Colposcopy-directed biopsy was assumed as the gold standard, and the accuracy of colposcopy at 6 months was assumed to be equal to that of immediate colposcopy. Out of 874 compliers, punch biopsy was performed in 303 cases (34.7%), and 19 CIN2+ lesions were detected (CIN2 = 12, CIN3 = 6, microinvasive carcinoma = 1). Detecting 13 CIN2+ lesions at colposcopy required 874 colposcopies and 303 directed biopsies: the cost per CIN2+ lesion detected with the procedure was 2,749 US$. Detecting 15 CIN2+ lesions at repeat cytology required 874 cytologic examinations, 137 colposcopies, 64 directed biopsies, and 6 diagnostic large-loop resections, the latter being performed in subjects with high-grade squamous intraepithelial lesion and less severe lesions at punch biopsy: the cost per CIN2+ lesion detected with the procedure was 1,961 US$. The policy of repeat smear was more cost-effective than immediate colposcopy. According to such results, the protocol of the Florence screening program has been modified since October 1996.     

Visual inspection of the uterine cervix after the application of acetic acid in the detection of cervical carcinoma and its precursors

BACKGROUND: Organized cervical cytology screening programs are not feasible in many developing countries where cervical carcinoma is an important cause of mortality among adult women. This study compared visual inspection of the cervix after application of 3-4% acetic acid (VIA, or cervicoscopy) with cytology as methods for the detection of cervical carcinoma and its precursors. METHODS: Three thousand women were examined by both VIA and cytology. Those positive on one or both of the screening tests (n = 423) or those who had clinically suspicious lesions even if the tests were negative (n = 215) were invited for colposcopy. Directed biopsies were obtained from 277 of 573 women at colposcopy. Those with moderate dysplasia or worse lesions diagnosed by histology were considered true-positives. Those with no lesions or with reactive or reparative changes at colposcopy and those for whom histology revealed no pathology, reactive or reparative changes, atypia, or mild dysplasia were considered false-positives. The detection rate of true-positive cases and the approximate specificity of the two tests were compared. RESULTS: VIA was positive in 298 women (9.8%), and cytology was positive (for atypia or worse lesions) in 307 women (10.2%). Of the 51 true-positive cases (20 cases of moderate dysplasia, 7 of severe dysplasia, 12 of carcinoma in situ, and 12 of invasive carcinoma), VIA detected 46 (90.1%) and cytology 44 (86.2%), yielding a sensitivity ratio of 1.05. VIA detected five lesions missed by cytology, and cytology detected three missed by VIA; both missed two lesions. The approximate specificities were 92.2% for VIA and 91.3% for cytology. The positive predictive value of VIA was 17.0%, and that of cytology was 17.2%. CONCLUSIONS: These results indicate that VIA and cytology had very similar performance in detecting moderate dysplasia or more severe lesions in this study. VIA merits further evaluation as a primary screening test in low-resource settings.     

Observer variability among colposcopists from the West Midlands region

OBJECTIVE: To assess variation in diagnoses and management decisions among colposcopists when presented with cervical images; to see the impact of the referral cytology report on diagnostic accuracy. DESIGN: A two-part video questionnaire study. PARTICIPANTS: Colposcopists from West Midlands Region. METHODS: Twenty cervical images displaying a range of transformation zones from normal through varying abnormalities up to cervical intraepithelial neoplasia (CIN) grade 3 were shown on video tape together with basic patient information. Two sets of videos were made, the second being identical to the first other than including the referral cytology. Participants recorded their diagnoses and management decisions on prepared questionnaires. The two sets of videos were viewed several weeks apart. RESULTS: Completed questionnaires to both videos were received from 30 colposcopists. Diagnostic accuracy improved with knowledge of the cervical cytology result in cases of CIN 2/3 (chi 2 = 19.45, P < 0.0001) but not where the histology was CIN 1 or less (chi 2 = 2.64, P = 0.10). Overall interobserver agreement improved slightly from kappa = 0.169 to kappa = 0.212 when the cytology was revealed. While only 2.6% of cases of CIN 2/3 would have been under-managed after the second questionnaire, 37.5% cases where the abnormality did not amount to CIN would have been overtreated. CONCLUSION: There is considerable inter-observer variability and variation in diagnostic accuracy in scoring cervical images particularly at the lower end of the spectrum of abnormality which has the potential to lead to over-treatment. We rely considerably on the cervical cytology result in forming a diagnosis. We recommend that a see-and-treat approach be abandoned when the referral smear shows minor abnormalities. The study has implications for both training and audit in colposcopy.     

2-(4-Aminophenyl)benzothiazoles: novel agents with selective profiles of in vitro anti-tumour activity

OBJECTIVE: To evaluate the results of cervical cytology screening in the National Breast and Cervical Cancer Early Detection Program and to compare the findings with results from other screening programs. METHODS: We analyzed data on 312,858 women aged 18 years and older who received one or more Papanicolaou smears, and follow-up if indicated, from October 1991 through June 1995 at screening sites across the United States providing comprehensive National Breast and Cervical Cancer Early Detection Program services. RESULTS: Of the women screened, more than half were 40 years or older; slightly less than half (44%) were of racial and ethnic minorities. During the first screening cycle, 3.8% of Papanicolaou tests were reported as abnormal (squamous intraepithelial lesion [SIL] or squamous cell cancer); proportions of abnormals decreased with increasing age. The age-adjusted rate of biopsy-confirmed cervical intraepithelial neoplasia (CIN) II or worse among women screened was 7.4 per 1000 Papanicolaou tests; rates of CIN were highest among young women, but cancer rates peaked among women in their 50s and 60s. The percentages of first screening cycle-Papanicolaou tests interpreted as high-grade SIL and squamous cell carcinoma associated with biopsy-confirmed CIN II or worse (the positive predictive value) were 56.0% for CIN II/III and 3.7% for invasive cancer. Of the 150 invasive cancers diagnosed, 54.0% were classified as local disease. CONCLUSION: Observed results emphasize the duality of cervical neoplasia-CIN in younger women and invasive cancer in older women. This finding points to the importance of reaching both younger and older women for cervical cancer screening.     

loop electrosurgical excision procedure: a review of our recent experience

OBJECTIVE: To investigated whether persistence or recurrence of cervical intraepithelial neoplasis (CIN) is associated with an involved excisional margin during loop electrosurgical excision procedure (LEEP). METHODS: The records of 256 consecutive LEEP were studied. After LEEP, all patients were followed up by colposcopy and cytology at 4 to 6 month intervals for at least two years. A patient was classified as having persistent disease if SIL was seen within one year of treatment or recurrent disease if SIL was detected after one year of treatment. All relevant patient details including cytology, colposcopy findings, treatment histology, complications, recurrence or persistence of disease entered into a computer database. RESULTS: Complications occurred in 8 patients (3.1%). LEEP was successful in treating 226 patients (95.4)%. Eleven patients (4.6%) had persistent SIL. Involvement of the resection margin was a significant risk factor for persistent disease (3.1% for uninvolved margins vs 11.4% for involved margins, P < 0.05). Similarly, recurrent disease occurred in 9.1% of patients with involved resection margins vs 2.1% with uninvolved margins (P < 0.05). Eleven patients (4.3%) had microinvasive carcinoma. Only 3 were identified by colposcopy and directed biopsy. CONCLUSION: LEEP is established as a safe and efficacious method for the treatment of CIN, long term morbidity including the effect on subsequent fertility must be observed.     

Effects of acetysal, dexamethasone and their combination on drug metabolizing enzyme systems in rat liver microsomes

One hundred and sixty-eight cases of cervical conization were performed for cervical intraepithelial neoplasia (CIN) in a 32-month study. The indications for conization were unsatisfactory colposcopic finding, abnormal epithelium that extended into the endocervical canal, a microinvasive cervical cancer, and significant discrepancy among cytology, colposcopy, and/or punch biopsy histology. In the early period of the study, conization was done by the cold-knife method (N = 107), whereas loop diathermy was used in the latter part of the study (N = 61). Both groups were similar in terms of age, indications for conization, and size of cervical cone specimens. Loop diathermy conization was done in a significantly shorter time (5.7 +/- 1.8 minute vs 15.2 +/- 6.1 minute)(P < 0.05) than cold-knife conization. However, the difference in the postoperative complications between loop diathermy(3.0%) and cold-knife conization(4.7%) was not significant. The incidence rate of residual CIN III lesions in the subsequent hysterectomy specimens, found by histological documentation on these specimens was 25.0 and 26.1 percent after loop diathermy and cold-knife conization respectively. These results suggest that loop diathermy is much easier to perform and a more time-conserving treatment modality than cold-knife conization in the management of patients with cervical intraepithelial neoplasia.     

Endoscopic ultrasonography for preoperative staging of esophageal carcinoma

OBJECTIVE: The objective was to determine the frequency with which regression or progression of disease without treatment occurred in women diagnosed with squamous cell cervical carcinoma in situ (CIS) during pregnancy. METHODS:. A retrospective chart review of all women evaluated at the University of Iowa Colposcopy Clinic diagnosed with CIS during pregnancy from 1987 through 1992 was used. Thirty-four women were evaluated during pregnancy, of which 26 also had postpartum evaluation. All pathology reports of initial cytology and biopsies, as well as colposcopic impressions, were reviewed and compared to the same evaluations postpartum. RESULTS: Of the 26 women evaluated both antepartum and postpartum, only 1 was treated (cone biopsy) during pregnancy. She had disease suspicious for microinvasion. She was disease free postpartum. Of the remaining 25, 20 (80%) had persistent disease, 2 (8%) had either missed disease or progressive disease postpartum, and 3 (12%) resolved without treatment at postpartum evaluation. No statistical significance was found between route of delivery and persistence (P = 0.34). No statistical significance was found between smoking and persistence of disease (P = 1.0). In 46% of women the initial cytology was CIN I or II, and the initial colposcopic impression was found to underestimate the severity of the disease in 35% of cases. Two women were found to have invasive disease postpartum. CONCLUSIONS: There is a high persistence rate of CIS complicating pregnancy. Given the relatively high rate of underestimation of disease severity by both cytology and colposcopic impression, the use of routine biopsy at the time of colposcopy is recommended. Invasive disease may be encountered on postpartum evaluation.     

Osteochondritis dissecans of the humeral head

ISSUES: The colposcope was developed in 1925 and is well established in clinical gynecologic practice for defining and delineating cytologically detected lesions mainly of the cervix but also the vagina and vulva. Additionally, various endoscopic procedures in gastroenterology, pulmonary and urologic lesions enhance the cytologic detection and histologic verification of precancerous and cancerous lesions. The cost-effectiveness of all these devices and their applicability, particularly in countries with a limited health budget, is a major issue. This task force considered aspects of the present state of the art and the challenges in the 21st century. CONSENSUS POSITION: Automated cytology can interface with colposcopic examination in a number of significant ways. Automated cytologic analysis of conventional cervical smears can potentially direct colposcopic examination by predicting the nature of a lesion, assist in determining which patients should receive colposcopy and, in some settings, thereby reduce the number of colposcopies. Potentially, various combinations of automated cytology and colposcopy may be used to generate screening protocols that might result in more effective and inexpensive screening. The role of cervicography, or high-resolution cervical photography, as a screening device remains to be defined. Sensitivity for high grade lesions is generally no greater than that in cytology, and specificity appears lower. The interpretation of cervical photographs in triage of mildly abnormal cytology may prove to be useful in countries with established cytology programs. In areas of the world where cytology screening programs are not in place, the interpretation of cervical photographs may have its most dramatic effect. Cost-effectiveness analyses are needed. There are, at present, insufficient data for the evaluation of speculoscopy, a procedure using chemiluminescent illumination of the cervix for visualization of acetowhite areas. Basic training in colposcopy should be integrated into the residency programs of obstetrics and gynecology. Criteria for the adequate training of colposcopists should be developed. Continuing education programs in colposcopy should be developed when they are not already in existence. The cost-effectiveness of integrating colposcopy as a primary screening technique should be evaluated. Following a high-grade squamous intraepithelial lesion (HSIL) cytology result, colposcopically directed punch biopsy should be taken with or without endocervical curettage. This generally should precede the loop electrosurgical excision procedure (LEEP); however, in certain circumstances direct LEEP may be indicated. LEEP under colposcopic vision is an efficient way to treat an HSIL lesion of the cervix because the histologic extent and margins can be determined, unlike with laser surgery or cryosurgery. It is also more cost-effective than cold knife conization because general anesthesia and an operating room are unnecessary. Following LEEP, the endocervical canal should be examined colposcopically for any evidence of involvement. Lesions in the endocervix can then be removed with a different-shaped loop. Further research into Raman spectroscopy as a diagnostic aid in cervical pathology is needed, as is the use of micrococolpohysteroscopy for in vivo cytologic analyses, especially of the endocervical canal and transformation zone. Hysteroscopy is the most direct method for the diagnosis and treatment of intrauterine diseases. Hysteroscopic endometrial biopsy is more accurate than conventional biopsy methods. Cervical invasion of endometrial cancer can be detected by hysteroscopy. The depth of invasion, however, is more accurately determined by magnetic resonance imaging or computed tomography. ONGOING ISSUES: Many topics for ongoing research and/or implementation are mentioned under "Consensus Position," above. (ABSTRACT TRUNCATED)     

Characterization of avian H5N1 influenza viruses from poultry in Hong Kong

The management of abnormal cytology during pregnancy has changed dramatically during the last 3 decades. The goal has been and remains timely diagnosis of and treatment planning for invasive carcinoma of the cervix. Because therapy for preinvasive disease can safely be postponed until the postpartum period, the ability to distinguish CIN from invasive cancer without cone biopsy has been a major step forward in the management of cervical disease in pregnancy. The data presented herein demonstrate the safety and accuracy of the more conservative approach of colposcopy and biopsy. The use of cone biopsy during pregnancy, associated with substantial morbidity, has been significantly reduced by the diligent application of colposcopy. As is true in the nonpregnant state, cone biopsy is necessary when colposcopic examination is nonsatisfactory. Cone biopsies cannot be considered therapeutic during pregnancy owing to the high incidence of positive margins and residual disease on postpartum evaluation. For this reason, the importance of postpartum reevaluation cannot be overemphasized.     

Management of cervical neoplasia with colposcopy

During a 44-month period the introduction of colposcopy to a metropolitan dysplasia clinic resulted in 1, 144 colposcopic examinations on 442 patients. Agreement between colposcopically directed biopsy and final diagnosis was found in 84%, and directed biopsy revealed the most advanced lesion in 42.5%. Satisfactory colposcopy was performed on 93% of patients, and some degree of histologic abnormality was obtained in 86% of patients with colposcopic abnormalities. Undetected invasive cervical cancer occurred in both cervical conization and colposcopic examinations with equal frequency. Endocervical curettage detected two cases of occult invasive cancer, and increased use of this procedure is recommended. Guidelines for management of cervical neoplasia are suggested.     

Multiple recurrences of cervical intraepithelial neoplasia in women with the human immunodeficiency virus

OBJECTIVE: To evaluate the long-term outcomes after treatment of cervical intraepithelial neoplasia (CIN) in women infected with the human immunodeficiency virus (HIV). METHODS: Human immunodeficiency virus-infected and HIV-negative women treated for CIN by ablation or excision were followed-up prospectively by cytology and colposcopy for periods of up to 73 months. RESULTS: Among 127 HIV-infected CIN patients, 62% developed recurrent CIN by 36 months after treatment, compared with 18% of the 193 HIV-negative CIN patients. Recurrence rates reached 87% in 41 HIV-infected women with CD4 counts less than 200 cells/mm3. Progression to higher-grade neoplasia, including one invasive cancer, occurred by 36 months in 25% of HIV-infected and 2% of HIV-negative women. After adjusting for age, CIN severity, and treatment type, predictors of recurrence included HIV infection (rate ratio 4.4), and, in HIV-positive women, low CD4 count (rate ratio 2.2). In patients treated by excision, predictors of recurrence included HIV infection (rate ratio 2.0) and residual CIN after treatment (rate ratio 2.7). After a second treatment,a second CIN recurrence developed in 14 of 33 HIV-infected and in one of 17 HIV-negative women. After a third treatment, three of six HIV-infected women developed a third recurrence. With long-term follow-up, 45% of treated HIV-infected CIN patients had chronic condylomatous changes in the cervix compared with 5% of HIV-negative women. CONCLUSION: In HIV-infected women, CIN may recur despite multiple treatments, and chronic condylomatous changes are common. Innovative therapies for controlling CIN in HIV-infected women are needed.     

Cervex-Brush vs. spatula and Cytobrush. A cytohistologic evaluation

OBJECTIVE: To compare the efficacy of two cervical smear instruments, Cervex-Brush and spatula plus Cytobrush. STUDY DESIGN: Cervical smears were taken before laser ring biopsies in 213 women, who were randomized for the Cervex-Brush or spatula plus Cytobrush (S+C). The cytologic diagnosis was compared to the histologic diagnosis after laser ring biopsy. RESULTS: The correlation between cytology and histology showed comparable concordance (54% and 42%) for the two devices. In 130 (74 with Cervex-Brush and 56 S+C) patients, histology revealed moderate dysplasia or more advanced lesions. Those cases were further analyzed for smear failures. Negative smears were found in 13 cases (10 in the Cervex-Brush and 3 in the S+C group). This difference in favor of S+C was not, however, statistically significant. Significantly more false negative smears were found when endocervical cells were absent and in patients 30-39 years of age. CONCLUSION: Modern sampling devices, such as the Cervex-Brush and S+C, seem to be equally efficient in obtaining dysplastic squamous cells. Other factors of importance for nonrepresentative cervical smears should be studied in order to improve efficacy.     

Clinical Significance of a cervical cytologic diagnosis of atypical squamous cells of undetermined significance. Favoring a reactive process or low grade squamous intraepithelial lesion

OBJECTIVE: To define the clinical significance of qualifying the cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS) as favoring either a reactive process or a low grade squamous intraepithelial lesion (LSIL) in an effort to provide management guidelines. STUDY DESIGN: A total of 118 consecutive nonpregnant women with a cytological diagnosis of ASCUS favoring either a reactive process or LSIL were evaluated in our colposcopy clinic by repeat cervical cytologic smear, colposcopy and colposcopically directed biopsies and/or endocervical curettage, as indicated. RESULTS: Of the 58 patients evaluated for a smear of ASCUS, favoring a reactive process, 5 (8.6%) had cervical intraepithelial neoplasia (CIN) CIN 1 documented by biopsy. None had a high grade lesion. Twenty-six (45%) of the 58 patients who had a cytologic diagnosis of ASCUS favoring a reactive process had a repeat smear that was normal. None was found to have CIN. Of the 60 patients who had a cervical diagnosis of ASCUS favoring LSIL, 9 (15%) had CIN 1 or CIN 2. Nineteen (32%) of the 60 patients who had a cytologic diagnosis of ASCUS favoring LSIL had a repeat smear that was normal. One of these patients had CIN 1 on biopsy. The sensitivity of a repeat smear, in this limited series, after an initial smear of ASCUS favoring a reactive process is 100%, while it was 66% after an initial smear of ASCUS favoring LSIL. CONCLUSION: This study showed that in our laboratory a cytologic diagnosis of ASCUS favoring either a reactive process or LSIL is associated with a very low risk that the patient is haboring CIN. In the patient whose initial smear shows ASCUS favoring a reactive process, a repeat smear that is normal is reassuring. The patient whose smear shows ASCUS favoring LSIL probably requires further evaluation even in the presence of a normal repeat smear.     

Observer agreement on interpreting colposcopic images of CIN

The purpose of this work was to study intraobserver and interobserver variation in the interpretation of colposcopic images of cervical intraepithelial neoplasia (CIN). Twenty-three experienced colposcopists were asked to assess colposcopic images presented on slides and to select the biopsy site. Eleven cases were independently interpreted twice with an interval of 2-3 months by all observers. No information about the cytological classification was available. In each case the "majority assessment" was considered as the standard, being "no CIN" in 2 cases, CIN I in 4 cases, CIN II in 3 cases, and CIN III in 2 cases. Intraobserver concordance was 66.7%, the kappa value was 0.54. Interobserver agreement was found to be 52.4 and 51.0% in the first and second sessions, respectively, while the mean kappa values were 0.41 and 0.33, respectively. In selecting the site for biopsy, 77.4% of all observers agreed while the same site was selected in 85.3% of cases by the individual colposcopist in the two sessions. Overall, CIN I and II interpretations revealed lower levels of agreement than no CIN or CIN III interpretations. It is concluded that observer variability in interpreting colposcopic images and selecting the site for biopsy is in the same range as observer variation in other subjective diagnostic tests such as cytology and histopathology. This variation should be taken into account in the colposcopical management of patients with abnormal cytology.     

Natural history of false-negative papanicolaou smears: a prospective study using screening colposcopy in addition to cytology

The regular Papanicolaou (Pap) smear is cornerstone of women's preventive healthcare. The introduction of the regular Pap smear as a screening tool for cervical cancer has markedly decreased the number of deaths from cervical cancer. During the past decade, however, the rate of death from cervical cancer has remained relatively static. This screening method is known to have a high rate of false-negative results; therefore, serial examinations are necessary for optimal sensitivity. The sensitivity of the routine pelvic examination is further increased with the addition of colposcopy to cytologic screening. Patients identified as having disease by colposcopy and biopsy but not by Pap smear (false-negative), are followed up, and the progression of their disease is documented until the Pap smear reflects the known change. A total of 276 patients whose Pap tests showed "no abnormal cells" and mild dysplasia (CIN-1 [cervical intraepithelial neoplasia]) by colposcopy and biopsy, who opted not to be treated, were followed up as a function of time. The results of the Pap test on the 276 patients progressed to a low-grade squamous intraepithelial lesion (LGSIL) or higher within 42 months. In this study, false-negative Pap tests that were identified by simultaneously performed colposcopy became positive within 42 months; therefore, careful repetitive screening is necessary. The author argues that a definitive, prospective study on the addition of colposcopy or similar adjunct procedure to the routine pelvic examination, in selected cases, is needed.     

Genetic damage in exfoliated cells of the uterine cervix. Association and interaction between cigarette smoking and progression to malignant transformation?

OBJECTIVE: To determine, through the micronucleus (MN) test, the cytogenetic effects of cigarette smoking on exfoliated cells from the uterine cervix in women with normal smears and women with inflammatory atypia, squamous intraepithelial lesion (SIL) (cervical intraepithelial neoplasia [CIN] 1-3) and cervical cancer. STUDY DESIGN: The study group consisted of 200 women divided into three subgroups: group 1 (n = 116), women periodically undergoing cervical cytology and residents of Salvador-Bahia; group II (n = 57), women residing in S?o Paulo and previously selected because of a possible cytopathologic test positive for such conditions as human papillomavirus infections or malignant or premalignant cervical lesions (CIN 1-3); group III (n = 27), inmates of the Tatuapé Penal Institution, S?o Paulo. All the women underwent cytologic and colposcopic examination, and biopsies were performed on 68 of them. RESULTS: Considering the samples as a whole and using the chi(2) test for rare events, the number of MNs in smokers was significantly greater than in nonsmokers. It was also greater in women with larger exposure to smoking. The occurrence of MN was significantly lower in women with normal smears (smokers and nonsmokers) than in those showing any kind of pathologic alteration. In nonsmokers the occurrence of MN was similar between those with inflammatory atypia (IA) or low grade (L) SIL (CIN 1) and significantly higher in women with more severe lesions or high grade (H) SIL (CIN 2 and 3). Smokers with LSIL (CIN 1) showed a higher number of MNs than nonsmokers with a comparable diagnosis and smokers with IA. No differences were observed when compared with smokers with HSIL (CIN 2 and 3). MN occurrence was not associated with other risk factors for SIL or cancer development, such as age at first coitus, number of sexual partners, multiparity and use of hormonal contraceptives. CONCLUSION: These results suggest that the mutagenic effect of cigarette smoking occurs in cervical cells and that the progression of SIL is associated with increased frequency of chromosomal damage. Moreover, the data suggest that cigarette smoking introduces an additional risk to the progression of low grade LSIL (CIN 1). MN testing would be helpful in monitoring smokers with this kind of lesion.     

Diagnosis and therapy of CIN in pregnant women

BACKGROUND: CIN is the most frequent neoplasm in pregnancy. At present, in Italy, Pap test and colposcopy are not included in routine examinations in prenatal visits. METHODS: In this study, we submitted 560 pregnant women to Pap test during prenatal visits. In case of abnormal or doubtful smears a colposcopy and target biopsy were performed. RESULTS: Of the 560 women studied, 124 had genital bleeding and the other 436 were asymptomatic. Six cases of CIN symptomatic women and 5 cases in the asymptomatic ones. In no cases we thought necessary a therapeutic operation. We limited the therapy to a follow-up. CONCLUSIONS: In our opinion, it is necessary to treat CIN during pregnancy.     

Genomic variation of human papillomavirus type 16 and risk for high grade cervical intraepithelial neoplasia

BACKGROUND: Epidemiologic studies have demonstrated strong and consistent associations between the detection of human papillomavirus (HPV) type 16 DNA and the risk of cervical intraepithelial neoplasia (CIN) and cervical cancer. However, HPV16 is also the most common type of HPV in the normal population, and only a minority of women with HPV16 infection develop cervical cancer. Studies of genomic heterogeneity in HPV16 have demonstrated the presence of multiple variant forms in all human populations examined to date. It is conceivable that the natural variants of HPV16 in a given population may not have the same biologic behavior. PURPOSE: This study was designed to determine the association between natural variants of HPV16 and the risk of biopsy-confirmed CIN 2 or 3, the most important precancerous lesions of the uterine cervix. METHODS: Prospective studies were conducted among 1) women attending a university and 2) women presenting to a sexually transmitted disease clinic. Subjects were eligible for inclusion in this investigation if the initial cytologic findings did not reveal CIN 2-3 and HPV16 DNA was detected by means of a polymerase chain reaction (PCR)-based method in one or more cervical or vulvovaginal samples. Eligible subjects were followed every 4 months with cervical Pap smears and colposcopic examinations. Women were referred for biopsy if cytology or colposcopy suggested CIN 2-3. Two groups of HPV16 variants, prototype-like and nonprototype-like, were determined by means of single-strand conformation polymorphism (SSCP) analysis of PCR products from the noncoding region of the viral genome. Representative SSCP patterns from HPV16 variants were further characterized by direct DNA sequencing of the PCR products. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated by Cox regression analysis. RESULTS: Prototype-like variants accounted for 79% of the HPV16 detected in university students and 86% of the virus detected in patients presenting to the sexually transmitted disease clinic. CIN 2-3 was confirmed by biopsy in nine of 57 HPV16-positive women attending the university and in 10 of 66 HPV16-positive women presenting to the sexually transmitted disease clinic. Among university students, those with HPV16 nonprototype-like variants were 6.5 (95% CI = 1.6-27.2) times more likely to develop CIN 2-3 than those with prototype-like variants. A similar association was observed among women presenting to the sexually transmitted disease clinic (RR = 4.5; 95% CI = 0.9-23.8). CONCLUSIONS: This study suggests that the risk of developing CIN 2-3 is not the same with all variants of HPV16 and that nonprototype-like variants confer a greater risk compared with prototype-like variants. The important genomic differences underlying this increased risk of CIN 2-3 remain to be determined.     

A repeated element in the regulatory region of the MNK gene and its deletion in a patient with occipital horn syndrome

Primary care physicians are in an excellent position to identify women most at risk for cancer precursors. They can use a variety of modalities, including colposcopy thus reducing patient anxiety and waiting time. This article describes a training program for such a service, which includes at least 100 colposcopy examinations under supervision. It is applicable outside a hospital clinic setting. Subsequent practice must have a referral base sufficient to maintain competence as well as economic viability. All GP colposcopists in the Perth area attend regular quality assurance meetings. An audit has shown that properly trained GPs can achieve a level of competence equivalent to that expected of their specialist colleagues (89% concordance between colposcopic impression and histology). The format of the audit was based on that of the Royal Australian College of Obstetricians and Gynaecologists (RACOG). Treatment must be performed by experts. General practice is the appropriate location for community screening studies using colposcopy.     

Diagnosis and therapy of cervical intraepithelial dysplasia in Austria: a survey

PURPOSE: To assess the present state of diagnosis, therapy and follow-up of cervical intraepithelial neoplasia (CIN) in Austria. MATERIAL AND METHODS: 100 questionnaires were sent to all departments of Gynecology and Obstetrics in Austria. The anonymous questionnaire consisted of 22 multiple choice questions. It was possible to choose one or more answers by ticking applicable boxes, with the option in individual cases of giving additional information in the form of free text. RESULTS: 55 (55%) departments returned their answered questionnaires, indicating growing consciousness of quality control in medicine. It was found that in the collection of cytologic specimens 67% of the departments used a wooden spatula and cotton swabs. Management of patients with Pap smears indicating low grade squamous intraepithelial lesion (LSIL) and abnormal colposcopy, in 36 (65%) departments consisted of punch biopsy for histological diagnosis. After 3 recurrent Pap smears indicating LSIL, 76% of the hospitals treated such patients by conization, regardless of the histological grade of the lesion. Following inadequate resection of CIN III by conization, operative management of patients was the most commonly used regimen. CONCLUSION: We regard the results of this survey as a basis for the development of further quality management strategies in the prevention, diagnosis and therapy of cervical intraepithelial neoplasia in Austria.