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.     

Lack of effect of coumarin on unscheduled DNA synthesis in precision-cut human liver slices

OBJECTIVE: To evaluate the accuracy of cytologic screening in pregnancy through routine colposcopy and to confirm the safety of conservative management of cervical intraepithelial neoplasia (CIN) in pregnancy. STUDY DESIGN: In total, 3,658 pregnant women, screened for cervical cancer with either cytology or colposcopy, were prospectively evaluated. Patients with abnormal findings underwent colposcopically directed biopsy and, in case of CIN, repeat cytology and colposcopy. Biopsy was repeated in case of suspected progression of the lesion. Suspected microinvasion was the only reason for diagnostic conization during pregnancy. After delivery, excisional treatment provided a final specimen from all patients. Diagnostic methods were compared. RESULTS: Comparison between cytology and colposcopy showed 97.1% concordance with a few false positives (2.5%) and false negatives (0.2%). Abnormal cytology and colposcopy, as compared with histology, showed similar concordances, but the risk of underestimation by cytology was significantly higher (P < .05). Initial and final histology of the 63 cases of CIN and microinvasive carcinoma showed 88.9% concordance. Progression of the lesion was not observed. CONCLUSION: These data do not justify combined use of cytology and colposcopy to improve screening for cervical cancer in pregnancy. Delayed treatment of CIN after delivery is safe.     

Independent clinical factors which correlate with failures in diagnosing early cervical cancer

Our aim was to identify independent factors that correlated with colposcopically directed biopsy's reliability as a method for diagnosing early cervical cancer. One hundred ninety-one of a total of 2265 patients who had colposcopic examinations because of abnormal Papanicolaou smears were included in this study. These patients had all undergone a hysterectomy after being diagnosed as having cervical intraepithelial neoplasia grade III by colposcopically directed biopsy. By univariate analysis, old age (P = 0.0195), achievement of menopausal status (P = 0.0046), large lesion size (P = 0.0021), and unsatisfactory colposcopy (P = 0.0017) were found to be associated with the nondiagnosis of early cervical cancer. However, multivariate analysis using stepwise logistic regression revealed that large lesion size (P = 0.003) and unsatisfactory colposcopy (P = 0.0008) were the only independent factors that correlated with nondiagnosis. Our findings indicate that in order to reach a clear-cut diagnosis, cases with either unsatisfactory colposcopy or satisfactory colposcopy with large lesions (despite a lack of histologic evidence of invasions) should undergo a diagnostic conization.     

Significance of a first-time atypical Papanicolaou smear in a young, high-risk African-American and Latino-American population

The first atypical Papanicolaou smear in young, sexually active Latino and African-American women of low socioeconomic status may be predictive of underlying cervical neoplasia and human papillomavirus infection of significant quantity. The optimal management of first-time atypia on routine Pap smear has not been established. In many clinics, colposcopically directed sampling of the cervix is recommended only if atypia persists following specific or nonspecific treatment of cervicitis or after an arbitrarily determined time interval. Others recommend immediate colposcopic evaluation. To determine the best approach to the first-time atypical Pap smear in young minority women at high risk for the development of cervical cancer, 250 such patients were evaluated with colposcopically directed biopsy of the cervix prior to any form of therapy. Pap smears were repeated at the time of colposcopy. Histologically, there was evidence of cervical intraepithelial neoplasia in 41% of patients and human papillomavirus infection in 86%. Repeat Pap smears predicted the presence of cervical intraepithelial neoplasia in only 24% of patients. Immediate colposcopic evaluation represents the most prudent approach to the first-time atypical Pap smear in young, high-risk minority women.     

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.     

Diagnostic conization of the uterine cervix. II. Comparison of histological diagnoses with cytological and colposcopic tentative diagnoses

This report presents colposcopic and cytologic misinterpretations in cases with a cervical intraepithelial neoplasia or early invasive carcinoma and benign cervical lesions and the accuracy of these two methods of screening for cervical cancer. The accuracy of the cytology and of the colposcopic impression in predicting the degree of cervical intraepithelial neoplasia and early invasive carcinoma was over 93 per cent. In patients showing benign cervical lesions the cytology is more accurate in predicting the correct histologic change with 94,2 per cent than the colposcopic impression with 63,1 per cent. The suspicious smears (Papanicolaou III) are discussed.     

Evaluating cervical neoplasia. LEEP as an alternative to cold knife conization

OBJECTIVE: To determine how the loop electrosurgical excision procedure (LEEP) compares to cold knife conization in providing an adequate diagnostic specimen. STUDY DESIGN: Between 1991 and 1995, 95 patients underwent either diagnostic LEEP or cold knife conization at Allegheny University Hospitals. The indications for the procedure were a cytologic/histologic discrepancy, unsatisfactory colposcopic evaluation, positive endocervical curettage or exclusion of invasion. RESULTS: Severe thermal artifact rendered the LEEP specimens uninterpretable in 4.4% of cases. A median number of two passes were required for LEEP excision of the transformation zone. The number of passes correlated with the amount of thermal artifact detected (P = .034). Regarding recurrence patterns, normal follow-up cervical cytology was similar for both groups: 96.7% in the LEEP group vs. 100% in the cold knife conization group. CONCLUSION: We conclude that LEEP is an acceptable diagnostic alternative to traditional cold knife conization. Thermal artifact remains a disadvantage that can be minimized by limiting the number of passes required to obtain a complete specimen.     

The "unsatisfactory" colposcopic examination

One hundred nine of 735 patients (14.8%) referred for colposcopic evaluation had "unsatisfactory" examinations. Of 108 women 40 years of age or over, 81 had unsatisfactory examinations (45%) as compared with 28 of 555 women under 40 (5%) (p less than 0.001). Thirty-five of the 109 patients with unsatisfactory examinations (32%) had had prior cautery or conization as compared with 141 of 626 in the "satisfactory" group (22.5%) (p less than 0.04). Seventy-three of the 99 patients on whom follow-up information was obtained had cervical conization biopsies for final diagnoses. Correlation with previously performed endocervical curettage and colposcopically directed biopsies was poor. Careful correlation of cytology, colposcopy and histopathology is necessary to achieve optimal results in the management of patients with unsatisfactory examinations. Diagnostic conization continues to play an important role in the management of patients with abnormal cervical cytology.     

Desulphation of heparin by mice and guinea pig leukocytes

A series of 603 patients referred with atypical Papanicolaou smears was evaluated by repeat smears, colposcopically directed cervical biopsies, and endocervical curettage. These techniques as a unit can establish an accurate outpatient diagnosis superior to any of these modalities used alone and comparable with findings in conization and hysterectomy specimens. Endocervical curettage has made a unique contribution to the evaluation of such patients; these curettings have allowed examination of tissue fragments and are more reliable in diagnosing neoplasia than are endocervical smears. Invasive carcinoma and its precursors confined to the anatomic endocervical canal can be recognized by this technique, and conversely the absence of neoplastic epithelium in adequate endocervical curettings rules out occult carcinoma. Indications for conization of the cervix are discussed in reference to the other biopsy and cytologic findings, and guidelines are presented for patient management, stressing clinicopathologic correlation and cooperation.     

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.     

Quality of life of women with stress urinary incontinence with or without pollakiuria]

BACKGROUND: The optimal management of low grade Papanicolaou (Pap) smear abnormalities remains controversial. This center's experience with recommending cytologic follow-up for women with atypical cells of undetermined significance (ASCUS) or low grade squamous intraepithelial lesions (LSIL) was reviewed to determine outcome and patient/physician compliance. METHODS: The records were reviewed on women with Pap smears reported as either ASCUS (320) or LSIL (112) who did not have a history of dysplasia. The cytologic and colposcopic follow-up for a 2-year period was obtained from the laboratory data base that includes the colposcopy and cancer referrals for this region. Repeat Pap smear in 6 months was recommended. If patients subsequently demonstrated high grade SIL (HSIL) or persistent ASCUS or LSIL over three time intervals, colposcopic evaluation was recommended. RESULTS: The outcome was determined by the most significant diagnosis among the follow-up Pap smears or colposcopic biopsies. 29% of patients were lost to follow-up. Of the remaining patients, 70.5% reverted to normal or benign cellular changes, 25.3% persisted as ASCUS or LSIL, and 5.2% progressed to HSIL. The majority of patients (68%) were referred for colposcopy for persistent mildly abnormal Pap smears. The timing of referral ranged from 3-30 months. CONCLUSIONS: These results suggest that cytologic follow-up of women with low grade Pap smear abnormalities will identify a large number whose smears will regress to normal. A small but significant proportion of women showed subsequent HSIL. Most HSIL was detected within 1 year of the initial abnormal Pap smear and the majority of intervening Pap smears also were abnormal. Approximately one third of patients did not have follow-up within the study system and their outcome was uncertain. Although the recommendations are standard, patterns of follow-up and referral to colposcopy varied widely, suggesting that the guidelines need to be reinforced to both patients and physicians. [See editorial on pages 1-4, this issue.]     

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.     

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.     

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.     

Conservative management of options for patients with dysplasia involving endocervical margins of cervical cone biopsy specimens

OBJECTIVE: Our purpose was to study the feasibility of conservatively managing selected cases of dysplasia involving endocervical cone margins. STUDY DESIGN: A retrospective review of patients conservatively managed after being found to have squamous cell dysplasia involving the endocervical margins of their cervical cone biopsy specimens. In phase I patients who had cold-knife conization with positive endocervical margins underwent repeat Papanicolaou smears and colposcopy, with biopsies and endocervical curettage as indicated. Those found free of disease were followed up with frequent Papanicolaou smears. In phase II patients with dysplasia to the endocervical resection edges on loop electrical excision procedure biopsy specimens were followed up with frequent cytologic studies. RESULTS: In phase I, 31 patients with positive endocervical margins on cold-knife conization and no evidence of dysplasia on reevaluation were followed up for 1 to 18 years. Dysplasia was detected in one patient during cytologic surveillance. In phase II, 11 patients were followed up for 12 to 31 months; only one patient has dysplasia. CONCLUSION: Selected patients with squamous cell dysplasia at endocervical cone biopsy margins may avoid additional surgery.     

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.     

Usefulness of early detection of uterine collum carcinoma

Systematic screening of preinvasive and invasive lesions of uterine cervix by exfoliative cytology is justified by present morphologic and physiologic knowledge of the cervical epithelium. This technically easy screening procedure should be performed by the family doctor. If the result is positive, the case should be turned over to the gynecologist. Systematic repeated screening permits nearly complete eradication of invasive cervical carcinoma.     

Cervical intraepithelial neoplasia in HIV seropositive patients

In order to assess the frequency of cervical intraepithelial neoplasia (CIN) in a high risk population, 32 women infected with human immunodeficiency virus (HIV), with no AIDS-related symptoms, underwent colposcopic, cytologic and histologic examinations of the uterine cervix. In seven cases (21.9%) cervical smears showed dysplasia and in nine cases (28.1%) histologic evaluation indicated CIN. No invasive carcinomas were observed. In seven of the nine women CIN was associated with lesions due to human papillomavirus infection (HPV). These data confirm that HIV-positive women are at increased risk for developing neoplasias in the lower genital tract and are in need of regular and careful cytologic and, in particular, colposcopic and histologic examinations.     

Colposcopic evaluation of patients with abnormal cervical cytology

A total of 1580 new patients underwent colposcopic evalution in the Dysplasia Clinic at Nassau County Medical Center. Of these patients, 186 had abnormal Papanicolaou smears associated with pregnancy, 150 were referred because of in utero exposure to diethylstilbestrol, and 1244 were referred because of abnormal cervical cytologic smear or suspicious cervical or vaginal lesion. Further analysis of this latter group revealed that 1184 (95%) patients had satisfactory colposcopic evaluation, and directed biopsy showed the following: 10 cases of invasive cervical carcinoma, 9 of carcinoma in situ with microinvasion, 118 of cervical carcinoma in situ, 110 of severe dysplasia, and 424 cases of mild to moderate cervical dysplasia. All of these patients subsequently were treated accordingly. Evaluation of final histologic specimen revealed a very high correlation with colposcopically guided biopsies. In 54 patients, where colposcopic evaluation was unsatisfactory, diagnostic cold knife conization was performed. Final histologic diagnosis disclosed a more advanced lesion in 30 patients (or 56%) of this group. The result of this study shows that satisfactory colposcopic evaluation is a highly accurate method of evaluation of abnormal cervical and vaginal cytologic smear.     

Pap smear screening in an urban STD clinic. Yield of screening and predictors of abnormalities

BACKGROUND: Pap smear screening studies in STD clinics have reported high rates of squamous intraepithelial lesions (SIL); however, there are limited data on levels of unsatisfactory smears of characteristics associated with cytologic abnormalities. GOAL: To assess the yield to Pap smear screening in an STD clinic and to evaluate the rates of and risk factors for atypia, low-grade SIL (LSIL), and high-grade SIL (HSIL). STUDY DESIGN: A chart review of the clinic records of women undergoing Pap smear screening between 1991 and 1994 was conducted. Results were assessed from two different screening protocols, the first using a Dacron swab to obtain the endocervical sample and the second using a cytobrush. RESULTS: Of 2034 Pap smears, 1313 (64.6%) were negative, 202 (9.9%) were unsatisfactory, 257 (12.6%) were atypical, 211 (10.4%) had LSIL, and 51 (2.5%) had HSIL. With the change to the cytobrush protocol, the rate of unsatisfactory smears decreased from 14.4% to 3% (p < 0.001), atypia increased from 10% to 16.7% (p < 0.001), and HSIL rose from 1.7% to 3.7% (p < 0.001). By multivariate analysis, atypia was associated with genital warts (odds ratio (OR) 1.53, 95% confidence interval (CI): 1.16-2.02); LSIL with younger age (p < 0.001, for trend), black race (OR 1.51, 95% CI: 1.08-2.10), genital warts (OR 1.81, 95% CI: 1.33-2.47), and an abnormal appearance of the cervix on examination (OR 2.49, 95% CI: 1.85-3.35); and HSIL with a previous abnormal Pap smear (OR 2.48, 95% CI: 1.08-2.10). Overall, abnormality rates were significantly higher in adolescents (35.5%) than older women (21.7%) (p < 0.01). CONCLUSIONS: Obtaining satisfactory Pap smears among women undergoing screening in an STD clinic is feasible and cytologic abnormalities are common. These results continue to support the need for Pap smear screening in STD clinics, but the high rates in adolescents, a group in whom the natural history of cytologic abnormalities has not been well-defined, raise questions about the need to develop age-appropriate screening and management strategies.