Colposcopic management of abnormal cervical cytology in pregnancy

Two hundred sixty-five pregnant women with abnormal Papanicolaou smears underwent colposcopy; 248 of them underwent directed cervical biopsies. Correlation of cytology with histology indicated concordancy within one grade in 202 of 241 patients (84%). Cytology was significantly more advanced than directed cervical biopsy in 15% and significantly less advanced in 1%. None of the 163 patients with moderate dysplastic cytology or less had microinvasive or invasive disease. Cervical conization was performed on 23 women, 4 of whom underwent modified radical hysterectomy for microinvasive carcinoma. Sixteen of 18 patients undergoing conization in pregnancy were available for postpartum follow-up and had persistent cervical dysplasia. Of 242 women followed conservatively, without pregnancy conization, 88 underwent postpartum evaluation. There were no false negatives in the antepartum evaluation of malignancy.     

Invasive cancer of the cervix in British Columbia: a review of the demography and screening histories of 437 cases seen from 1985-1988.

The charts of 437 patients with newly diagnosed invasive cervical cancer seen in British Columbia during 1985-1988 were reviewed to determine the age at diagnosis, stage of disease, and histology of the lesions. The patient's immigration status and country of birth were also examined. Two hundred forty-two patients (55%) were age 50 or over and 149 (34%) had preclinical stage IB disease. One hundred seventy of these patients (39%) had never had a cytologic examination before presenting with clinical symptoms, and 45 additional patients had not had cytology for 5 or more years before presenting with invasive disease; thus, a total of 215 cases (49%) fell into the category of "no cytology or cytology longer than 5 years ago." All negative smears were reviewed and in 39 patients (15%) having previous cytology, abnormal cells had been missed or undercalled. Native Indian women made up 10% of the cases of invasive carcinoma, a disproportionately large number as they represent only 2% of the British Columbian population. Of the 27 Native Indian patients in this series, 16 (59%) had never had a cytologic examination. Eighty-five (30%) of 276 women born in Canada had never had a cytologic examination, compared with 34 (71%) of 48 immigrants resident in the country for fewer than 10 years. Twenty-four patients were over the age of 60 with a history of negative Papanicolaou smears. We conclude that, if further gains are to be made in the reduction of death rates from invasive cervical carcinoma, new means must be found to encourage women to participate in Papanicolaou smear screening programs. In particular, special efforts must be made to attract specific groups, such as the Native Indian population and older recent immigrants.     

How frequently need vaginal smears be taken after hysterectomy for cervical intraepithelial neoplasia?

A retrospective longitudinal review identified 341 women who had had a hysterectomy in association with CIN 3, in Tayside Region, during the years 1967-1977; 219 (64%) had completed 10 years of cytology follow-up and of 140 women eligible for 15-year smears 79 (56%) completed the 15-year follow-up. Eight (4%) of the 219 patients developed abnormal cytology, but in six, smears reverted to normal spontaneously. Two patients had persistently abnormal smears and vaginal intraepithelial neoplasia (VAIN) was diagnosed. Only one patient completing 15-year follow-up had an abnormal smear and VAIN later diagnosed. No patient over this 15-year period developed invasive vaginal carcinoma. Sixty vaginal carcinomas were identified during the period 1957-1987 from the gynaecology cancer register; only one was associated with a previous diagnosis of CIN 3 at hysterectomy. With such data we would propose screening 6-monthly during the first post-operative year and then at 2 years. If these smears were normal, the patient could then revert to the normal screening programme.     

How frequently need vaginal smears be taken after hysterectomy for cervical intraepithelial neoplasia?

Summary. A retrospective longitudinal review identified 341 women who had had a hysterectomy in association with CIN 3, in Tayside Region, during the ycars 1967–1977; 219 (64%) had completed l0 years of cytology follow-up and of 140 women eligible for 15-year smears 79 (56%) completed the 15-year follow-up. Eight (4%) of the 219 patients developed abnormal cytology, but in six, smears reverted to normal spontaneously. Two patients had persistently abnormal smears and vaginal intraepithelial neoplasia (VAIN) was diagnosed. Only one patient completing 15-year follow-up had an abnormal smear and VAIN later diagnosed. No patient over this 15-year period developed invasive vaginal carcinoma. Sixty vaginal carcinomas were identified during the period 1957–1987 from the gynaecology cancer register; only one was associated with a previous diagnosis of CIN 3 at hysterectomy. With such data we would propose screening 6-monthly during the first postoperative year and then at 2 years. If these smears were normal, the patient could then revert to the normal screening programme.     

Evaluation of Serial Cervical Cytology in the Assessment of Preinvasive Cervical Neoplasia

Examination was made of the cervical cytology in 107 patients who underwent cone biopsy with a subsequent diagnosis of severe dysplasia or carcinoma in situ (105) or microinvasive carcinoma (2). Multiple smears had been performed for each patient over a period of time. From the total number of smears a 'false-negative' cervical cytology rate of 10.3 per cent was found. The time interval from the initial abnormal smear until definitive surgical treatment was carried out was calculated. The cervical smear prior to cone biopsy was found to correlate with the histological diagnosis in only 46.7 per cent. The implications of performing repeated cervical cytology are discussed and a firm recommendation is made that patients with abnormal cervical smear be promptly referred to definitive treatment.     

Comprehensive cytologic screening in patients undergoing voluntary abortions

This is a report of comprehensive cervical screening performed for all patients requesting abortion at the New York Medical College Metropolitan Hospital center from July 1, 1970 through December 1, 1972, a total of 6619 patients. Those with negative cytology had abortions performed. At first patients with abnormal smears had multiple punch biopsies and endocervical curettage at the time of uterine evacuation. They remained hospitalized until the pathology report was available. Later the uterine evacuation was deferred and patients with abnormal smears were referred to the colposcopy clinic where the atypical areas of the transformation zone were biopsied and the endocervical canal curetted. Cervical conization was performed immediately following suction curettage in patients with carcinoma in situ and in patients with severe dysplasia. Of the 6619 patients, 6367 had negative smears, 160 atypical, 28 with moderate or severe dysplasia or carcinoma in situ, and 2 invasive carcinoma. Of the 160 with atypical cytology cervical punch biopsies were negative in 104 with mild dysplasia in 56. Of the 28 with more severe changes cervical punch or cone biopsy revealed carcinoma in situ in 16, severe dysplasia in 5, moderate dysplasia in 5, and mild dysplasia in 2. The 2 patients thought to have invasive carcinoma were shown to have carcinoma in situ. Invasive carcinoma was not shown in any woman requesting pregnancy termination. Mean age of the 30 patients with severe changes was 24.7 years, the youngest 19 and the oldest 28. Mean parity of this group was 3. Ethnic background of all patients was similar to the population served. Age range for the total group was 13 to 42 years with 90.6% under 30 and 60% para 1 or less. When concimitant sterilization was desired hysterectomy was performed in cases of moderate dysplasia as well as severe dysplasia and carcinoma in situ. Patients with dysplasia are thought to run almost 100 times the risk of cervical cancer than those with negative smears. Cytologic screening is considered an integral part of any abortion program.     

False-negative Pap smear in uterine malignancy

For the period 1964 to 1976, Papanicolaou smears of 384 patients with uterine malignancies admitted to Cook County Hospital were studied. There were 36 negative Pap smears in a group of 307 patients with invasive cervical carcinoma (11.7% false-negative rate), and three negative Pap smears in a group of 45 patients with in situ squamous cell carcinoma of the cervix (6.6% false-negative rate). Forty-seven of 77 patients with endometrial carcinoma had negative cytologic examinations (51.9% false-negative rate). Because routine cervicovaginal cytology is not as satisfactory for the detection of endometrial carcinoma as it is for squamous cell carcinoma of the cervix, the importance of other screening techniques for endometrial carcinoma is discussed.     

Automated quantitative fluorescent image analysis of cervical cytology

Cervical cytology from 122 patients with histories of one or more abnormal Pap smears were studied using slide-based automated quantitative fluorescence image analysis (QFIA) in order to determine the usefulness of the QFIA technique in detecting neoplasias. The purpose of the study was to evaluate the accuracy and validity of QFIA as a cytological method for the early detection of cervical cancer, based on comparisons with the conventional Pap smear and histopathology. The results of the analysis demonstrated that the sensitivity of the automated QFIA cytology was 100% for high-grade neoplasms (CIN III and invasive carcinoma), compared with 82% for the Pap smear. Evaluation of lower grade neoplasms was also performed. Initial analyses of the data indicate that QFIA, which uses objective biochemical criteria to identify cells with increased nuclear nucleic acid content, is a more sensitive detector of cervical neoplasia of all grades than is conventional Pap cytology.     

A comprehensive program for cervical cancer detection and management.

OBJECTIVE: The purpose of this study was to document some of the results of a comprehensive provincial cytology and colposcopy program for the year 1988 and also to review the impact on the incidence and mortality rates for a clinical carcinoma of the cervix. STUDY DESIGN: This study is a retrospective analysis of the cytologic results of all patients examined provincially in 1988 and a review of the clinical records of patients diagnosed with invasive cancer and those who died of disease. RESULTS: In 1988 490,985 women (40% of all women over the age of 15 in the population) were screened, with 9.2% showing abnormal cells. A total of 79% of women screened were less than 50 years old and accounted for 86.3% of all abnormal smears. Women less than 35 years old were more likely than older women to have moderate dyskaryosis or worse. CONCLUSION: Intensive comprehensive cytology and colposcopy programs reduce not only the incidence and mortality of clinical carcinoma of the cervix but also rates of in situ disease and other precursors.     

The invasive potential of carcinoma in situ of the cervix

Nine hundred and forty-eight patients with carcinoma in situ (CIS) of the cervix diagnosed histologically have been followed from five to 28 years. Among the 817 patients who had normal cytology follow-up, 12 (1.5%) developed invasive carcinoma. A second group of 131 patients continued to produce abnormal cytology consistent with cervical neoplasia, and 29 (22%) of them developed invasive carcinoma of the cervix or vaginal vault. Patients with continuing abnormal cytology after initial management of CIS of the cervix are 24.8 times more likely to develop invasive carcinoma than women who have normal follow-up cytology. Further, when compared with the population at large, the chances of patients with normal follow-up cytology developing invasive cervical or vaginal vault carcinoma increase 3.2-fold over women who have never had CIS of the cervix.     

Aggressive evaluation for atypical squamous cells in Papanicolaou smears

A retrospective study was done on women who had atypical Papanicolaou smears and were referred for immediate colposcopy. The smears were obtained during January 1985 to March 1989 at Edwards Air Force Base, California. Excluded from the evaluation were abnormal Papanicolaou smears with hyperkeratosis, parakeratosis and koilocytotic atypia suggestive of human papillomavirus (HPV) infection. The evaluation included colposcopy, colposcopically directed biopsies, endocervical curettage and repeat Papanicolaou smears. A total of 101 patients were included in the study. Cervical intraepithelial neoplasia (CIN) was seen in 29.7% (30 patients): 12.9% (13) CIN I, 12.9% (13) CIN II and 3.9% (4) CIN III. Carcinoma was seen in 3.9% (4) of the patients: 2.9% (3) was carcinoma in situ, and 0.99% (1) was invasive squamous cell carcinoma, stage IIb. HPV and dysplastic lesions were seen together in 19.8% (20) of the patients. HPV was seen alone in 45% (46). Twenty-one patients (20.8%) had no apparent lesions on colposcopy, although one developed microinvasive keratinizing squamous cell carcinoma within 36 months of colposcopy. Many significant lesions can go undetected for extended periods of time in women with atypical Papanicolaou smears, resulting in delayed management. Referral for immediate colposcopy is advocated strongly.     

Cervical cytology in folic acid deficiency of pregnancy

Abnormal cervical cytology was discovered among pregnant women demonstrating deficient levels of serum folate, neutrophil hypersegmentation, and megaloblastic bone marrow maturation. In a double blind evaluation, the abnormal cells were not seen on smears acquired from a control group of normal pregnant patients. Cytologic preparations obtained later in the developing deficiency state had a greater chance of showing abnormal cytology. Therefore, this cellular change precedes overt folate depletion in pregnancy by many weeks and represents another subclinical manifestation of the disease. With folic acid therapy, the observed cytologic alterations may revert to normal in a period of days. It is apparent that squamous cell alterations in vaginal smears of pregnant patients do not necessarily reflect precancerous lesions. The finding of abnormal cytology in pregnancy, while demanding conventional investigation, should suggest the possibility of associated folic acid deficiency.     

'Abnormal' Papanicolaou smears and colposcopy in pregnancy: ante- and post-partum findings

Abnormal Papanicolaou smears and colposcopic findings suggesting human Papilloma virus (HPV) infection and cervical intraepithelial neoplasia (CIN) may occur during pregnancy. Condylomata acuminata often grow rapidly during pregnancy and may regress spontaneously following delivery. However, the post-partum outcome of the untreated ante-partum abnormal cytologic smear and colposcopy has not been defined clearly. Seventy-three pregnant patients were examined by colposcopy because of genital warts and/or abnormal Papanicolaou smears. Cytologic, colposcopic and histologic re-evaluation was conducted after delivery. Only one of the patients had a normal ante-partum colposcopic examination. This number increased to 15 after delivery. Forty-one patients had normal post-partum cytologic smears, but only 13 had normal histology. Abnormal post-partum cytology was highly predictive of abnormal colposcopy and histology. In contrast, normal post-partum cytology was not very accurate in predicting normal colposcopy and histology. It is concluded that a few pregnant patients may have partial regression of clinical HPV infection and abnormal cytology and colposcopy after delivery. However, the majority will continue to have abnormal findings 4 months following delivery in spite of normal post-partum cytology and even colposcopy.     

Positive predictive value of liquid-based and conventional cervical Papanicolaou smears reported as malignant

OBJECTIVES: The predictive value of cervical Papanicolaou (Pap) smears reported as "positive for malignancy," especially those obtained by the liquid-based method, has not been adequately assessed. The objectives of this study are to determine the positive predictive value of Papanicolaou smears with features of malignancy, to compare the accuracy of Papanicolaou smears obtained by the liquid-based method to those obtained by the conventional technique in this setting, and to study the factors influencing a false-positive cytologic diagnosis of malignancy. MATERIALS AND METHODS: Pap smears significant for malignant cytology were identified at Fletcher Allen Health Care Hospital in Burlington, VT, from May 1, 1995, to April 30, 2001. A retrospective review of the hospital records and pathology reports was performed documenting patient characteristics, the collection technique, and the final histology. An independent review of the cytology and histology was performed. The positive predictive value and false-positive rate of malignant cytology were calculated for the liquid-based and conventional Pap smear techniques. RESULTS: A total of 472,743 Pap smears were performed during the period specified. One hundred four Pap smears were reported as positive for malignancy, yielding a prevalence rate of 0.02%. A total of 68 patients had paired cytology and histology specimens. Malignant cytology was identified in 36 smears obtained by the liquid-based technique and 32 smears obtained by the conventional technique. A true-positive result, meaning malignant cytology confirmed by the presence of invasive carcinoma on histology, was obtained in 61 of 68 (89.7%) patients. A false-positive result, meaning malignant cytology not confirmed by histology, was obtained in 7 of the 68 (10.3%) patients. The false-positive rate of malignant cytology was 8.4% for the liquid-based technique and 12.5% for the conventional technique. All 7 false-positive smears were diagnosed with high-grade dysplasia by histology. Three of the 7 patients with high-grade dysplasia had previous treatment for dysplasia, one of whom was also pregnant at the time of the smear. CONCLUSIONS: Malignant cervical Papanicolaou smear cytology has a high positive predictive value in the setting of gynecologic and nongynecologic malignancies. Previous treatment for cervical dysplasia or pregnancy may influence the false-positive rate of malignant cytology.     

Colposcopic evaluation of patients with abnormal cervical cytology.

Because of suspicious or abnormal smears, 620 patients were referred to the Colposcopy Clinic of the British Columbia Cancer Institute between 1st March 1973 and 31st December 1974; it was possible to make a colposcopic examination in 549 of these patients (88.5 per cent). The colposcopic impression was within one histological grade of a colposcopically-directed biopsy in 476 patients (86 per cent). There were 221 patients who had a cone biopsy after a colposcopically-directed biopsy and in 192 of these (87 per cent) the two biopsies were within one histological grade of each other; but there were two patients with occult invasive carcinoma in a cone biopsy and only carcinoma in situ in a directed biopsy. In the same group of 221 patients the colposcopic evaluation and final diagnosis (the most advanced histological lesion seen in biopsy) agreed in all but seven patients.     

Different Detectability of High-Risk HPV in Smears from Incident and Prevalent High-Grade Squamous Intraepithelial Lesions of the Cervix

Human papillomavirus (HPV) status in cervical smears from cervical intraepithelial neoplasia (CIN) 2/3 diagnosed in 36 of 892 women with a history of normal cytology and colposcopy (incident CIN 2/3) was compared with CIN 2/3 in 40 patients with a history of abnormal cytology (prevalent CIN 2/3). In all patients cervical smears for HPV testing and cytology and two cervigrams were taken. The scrapes were collected in hybrid capture assay solution and analyzed with the hybrid capture and general primer/type-specific primer polymerase chain reaction system (GP/TS-PCR) after DNA extraction. Patients with incident and prevalent CIN 2/3 were similar with respect to age. By GP/TS-PCR carried out under suboptimal conditions due to DNA extraction, HPV DNA was detected in 69.4% (25 of 36) of smears from incident CIN 2/3 compared to 95% (38 of 40) in prevalent CIN 2/3 (P= 0.003). Using hybrid capture, smears of incident CIN 2/3 were HPV positive in 50% (18 of 36) compared to 80% (32 of 40) in prevalent CIN 2/3 (P= 0.006). High-risk HPVs were significantly less common in smears from incident CIN 2/3 compared with prevalent CIN 2/3: 36.1% vs 72.5% by GP/TS-PCR (P= 0.001) and 47.2% vs 80% by hybrid capture assay (P= 0.003), respectively. Virus load in HPV-positive smears of prevalent CIN 2/3 was significantly higher than of incident CIN 2/3 using semiquantitative PCR (P= 0.0005). Thus, high-risk HPV types were detected less frequently and in lower concentration in smears from incident CIN 2/3 than in smears from prevalent CIN 2/3.     

Previous cytology in patients with carcinoma of the cervix

The cytologic history of 317 patients with uterine cancer, in a mass survey using mobile units, was reviewed. They included 152 cases of carcinoma in situ of the cervix, 151 cases of invasive epidermoid carcinoma of the cervix, 11 cases of adenocarcinoma of the cervix, one case of verrucous squamous cell carcinoma and 2 cases of adenocarcinoma of the endometrium. There was no history of cytology in 17.1% of CIS or in 29.8% of invasive epidermoid carcinoma in the preceding 3 years (same order in the following); in the preceding 5 years the figures were 24.3% and 23.6% respectively. Suspicious or positive cytology noted more than once were 22.2% and 21.7% in the preceding 3 years, and 24.3% and 23.6% of the cases in the preceding 5 years. At least 2 negative Papanicolaou smears were 19.1% and 20.5% in the preceding 3 years, and 28.3% and 28.5% of the cases in the preceding 5 years. The yearly rate of suspicious and/or positive cytology in the preceding 5 years fluctuated between 13.5% and 30.4% in CIS, and between 9.1% and 23.0% in invasive epidermoid carcinoma. They showed no significant rise or trend. Verrucous squamous cell carcinoma as well as adenocarcinoma of the cervix and of the endometrium not infrequently showed successive negative cytology.     

Cytologic cancer prevention with smears of the uterine cervix and endocervical canal in pregnancy]

This study was performed to evaluate the importance of obtaining prepartum Papanicolaou smears routinely. 1,417 patients receiving pregnancy care had normal prenatal Pap smears. 88 (5.85%) had abnormal prepartum Pap smears. Thirteen (14.8%) of the abnormal smears showed squamous dysplasia, 2 (2.3%) showed an adenocarcinoma or squamous invasive carcinoma. The results of this study support the practice of performing Pap smears during prenatal care.     

Should patients with mild atypia in a cervical smear be referred for colposcopy?

Summary. Significant premalignant disease of the cervix was found in 37% of women referred to a colposcopy clinic because of a smear that showed no more than mildly atypical cells, and in 49% of women whose smears showed mild dyskaryosis. This did not seem to be related to the number of times the abnormal smear had been repeated and was not confined to patients whose smears had been reported by only one laboratory. In another group of 102 women whose first abnormal smear was graded as atypical: 10 had cervical intraepithelial neoplasia; 9 still had abnormal smears and 27 had been lost to follow-up, possibly because the potential importance of this finding was not recognised by the doctor to whom the smear report had been returned. Women with mildly atypical or mildly dyskaryotic smears are at considerable risk of having cervical intraepithelial neoplasia. All patients with a smear report showing dyskaryosis of any degree of severity should be referred for colposcopy. Those with atypical cytology should be referred for colposcopy if a second smear, repeated after 3 months, is not normal.