Management of cervical neoplasia: a 13-year experience with cryotherapy and laser.

OBJECTIVE: To evaluate whether cryotherapy is as effective as laser therapy in treating cervical intraepithelial neoplasia (CIN), and to determine the optimal time for follow up. MATERIALS AND METHODS: Patients with biopsy-proven CIN were treated with cryotherapy or laser therapy. Specific data, including grade of CIN, rate of recurrence, and time to recurrence, were compared between the groups. RESULTS: From 2240 eligible patients, 1126 were treated with laser and 1114 with cryotherapy. Ninety-two percent of patients in the laser group and 91.6% in the cryotherapy group had no evidence of CIN after a median follow up of 60 months. The 183 patients with recurrent/persistent disease were retreated with the same treatment modality as initially received. Eighty-seven of the 90 (96.7%) patients retreated with laser and 90 of the 93 patients (96.8%) retreated with cryotherapy had no further evidence of CIN. The majority (128 out of 183; 75.4%) of recurrent/persistent disease was detected within 18 months after treatment. CONCLUSIONS: CIN can be treated with similar success by cryotherapy or laser ablation. Optimal follow up would be two years for CIN1 lesions and five years for CIN2/3 lesions.

Infrared spectroscopy of exfoliated cervical cell specimens. Proceed with caution.

OBJECTIVE: To determine whether diagnostic information may be recovered from the infrared spectra of exfoliated cell specimens by using a novel spectral feature extraction method, in conjunction with linear and quadratic discriminant analysis, for spectral classification. STUDY DESIGN: Over 800 infrared spectra were included in the study, with corresponding clinical diagnoses based upon cytology and, when available, histology reports. Three sets of classification trials were carried out with the aim of distinguishing the spectra corresponding to normal specimens from CIN 1, 2 and 3. For each of these three cases, the procedure was to: (1) develop a set of provisional classification models using only a "training" subset of the spectra, and (2) test each provisional model by its ability to correctly predict the diagnoses on the basis of the remaining spectra. RESULTS: For optimal classification trials, training set classification accuracies were 68% for normal/CIN 1, 73% for normal/CIN 2 and 81% for normal/CIN 3; for the corresponding test sets the classification accuracies were 60%, 60% and 67%, respectively. CONCLUSION: The infrared spectra of exfoliated cervical cells carry information regarding the presence or absence of dysplasia, and that information is recoverable--albeit imperfectly at this stage--from the spectra of "real life" cell preparations.

The effect of vaginal microbes on in vivo and in vitro expression of human papillomavirus 16 E6-E7 genes.

Since other viruses can influence expression of human papillomavirus (HPV) 16 E6-E7 genes in vitro, this study addressed whether specific vaginal bacteria do so as well. The vaginal microflora of 18 women with cervical intraepithelial neoplasia (CIN) or normal histology and HPV 16 infection, was evaluated by quantitative culture. Expression of HPV 16 E6-E7 oncogenes was assessed in exfoliated cervical cells by quantitative polymerase chain reaction. HPV 16 expression was also quantitated in CaSki carcinoma cell line cocultured with Bacteroides fragilis or Lactobacillus acidophilus. Isolation of Lactobacillus sp. (p = 0.05) and expression of the E6*II transcript (p = 0.03) were associated with low-grade CIN or normal histology. However, changes in E6-E7 expression were not associated independently with isolation of a specific microorganism. Similarly, expression of HPV 16 E6-E7 oncogenes in vitro was unaltered in the presence of bacteria. These results suggest that vaginal microorganisms are unlikely to alter the natural history of HPV-associated CIN by influencing HPV oncogene expression.

Brush vs. spatula for cervical smears. Histologic correlation with concurrent biopsies.

In this study we compared the results of 1,293 brush smears obtained between April 23, 1990, and April 22, 1991, with those of 1,304 consecutive spatula smears from 1989. As expected, 94.1% of brush smears revealed the presence of endocervical cells as compared to 63.04% of the spatula smears (P < .0001). The number of "normal" cases was significantly (P < .001) lower in the brush smears (58.2% for the brush vs. 73.7% for the spatula). A significantly larger number (P < .001) of "abnormal" cases and low and high grade squamous intraepithelial lesions (moderate, severe, carcinoma in situ) were demonstrated in the brush smears. In the second part of the study the results of 547 brush smears with accompanying cervical biopsies obtained during the same period were studied for concordance of interpretation and were compared with 421 biopsy-accompanied spatula smears. Of the brush cases, 17.6% cytologically reported as high grade squamous intraepithelial lesions had low grade squamous intraepithelial lesions or reactive or normal histology. This discrepancy was significantly lower (P < .05) in spatula cases (8.9%). These findings suggest that in this series, although brush sampling yielded a higher pickup, it led to a tendency toward overinterpretation by cytopathologists.

Quantification of HPV-16 E6-E7 transcription in cervical intraepithelial neoplasia by reverse transcriptase polymerase chain reaction.

Human papillomavirus type 16 (HPV-16) is associated with neoplastic lesions of the uterine cervix. Viral transforming functions have been localized to the E6-E7 open reading frame (ORF) and this ORF is conserved consistently in cervical intraepithelial neoplasia (CIN). Two mRNAs, generated by alternative splicing, are expressed from the E6-E7 ORF. These are known as E6*I and E6*II, and potentially encode the viral E7 and E6 proteins, respectively. It is believed that the HPV-16 transforming ability is mediated by the E6 and E7 proteins. A quantitative RT-PCR assay, developed by us to characterize the relative expression of E6-E7 spliced transcripts, was applied to exfoliated cervical cells obtained from patients in varying stages of clinically defined CIN and who were infected with HPV-16. The relationship between viral expression, disease stage, oral contraceptive use and age was studied. No association was observed between age or oral contraceptive use and HPV-16 E6-E7 expression. However, when both E6*I and E6*II were detected, a direct correlation was observed between relative proportions of E6*I/E6*II mRNAs greater than 95%/5% and increased disease severity. This study underscores the importance of the relationship between quantities of viral transforming gene transcript and the course of cervical disease. It also suggests that quantification of HPV-16 E6-E7 transcription may be useful as a prognostic tool to identify women who are at increased risk of developing cervical cancer.

Effect of the menstrual cycle on detection and typing of human papillomavirus in uterine cervical cells.

We observe fluctuations in human papillomavirus detection and variation in genotyping between sequential cervical cell specimens analyzed by filter in situ hybridization. Furthermore, specimen adequacy for analysis varies. To determine whether these phenomena are correlated with menstrual cycle stage at the time of sampling, we analyzed cervical cell specimens from women with cervical intraepithelial neoplasia. Specimens were categorized on the basis of a 28-day menstrual cycle and were analyzed by hybridization to combined probes for virus types 6 and 11 or types 16 and 18. Specimen adequacy was determined by hybridization to a human Alu I repetitive deoxyribonucleic acid probe. Analysis of data with chi 2 revealed that fluctuations in virus detection and type variation are unrelated to menstrual cycle stage. Specimen adequacy is stage-dependent for women who take oral contraceptives. Whereas specimens can be collected at any time other than the first week of the menstrual cycle, accurate determination of infection status requires multiple assessments.

Comparison of filter in situ deoxyribonucleic acid hybridization with cytologic, colposcopic, and histopathologic examination for detection of human papillomavirus infection in women with cervical intraepithelial neoplasia.

Material from uterine cervical scrapings of 98 women with cervical intraepithelial neoplasia were analyzed by filter in situ hybridization for human papillomavirus infection. Concurrently obtained Papanicolaou smears and colposcopically directed biopsy specimens were also examined for papillomavirus infection. Hybridization was superior to cytologic and colposcopic examinations and was equivalent to histopathologic study for papillomavirus detection. Infection with virus types 6 and/or 11 was associated with milder disease, whereas virus types 16 and/or 18 infection alone or in association with types 6 and/or 11 was associated with more severe disease. Because papillomavirus infection may not be detected by cytologic or colposcopic examination and specific virus types have been documented to be associated with invasive disease, deoxyribonucleic acid hybridization analysis for at least these virus types should be carried out in conjunction with conventional procedures when evaluating women with cervical disease. Filter in situ hybridization is a simple, rapid, noninvasive procedure and has enhanced diagnostic value over conventional procedures by defining infecting virus types.

Mucometra: a rare complication of cryosurgery.

In a series of 400 patients treated for cervical intraepithelial neoplasia, 3 developed a clinical picture 6 days after the procedure that consisted of lower abdominal pain and uterine cramps. Examination revealed a closed os; on probing of the cervix, a large amount of mucus (approximately 60 ml) under tension was drained, after which there was almost immediate relief of the symptoms.

The association of sexually transmitted diseases with cervical intraepithelial neoplasia: a case-control study.

Thirty-three women with histologically confirmed cervical intraepithelial neoplasia (grades I to III, with one case of microinvasive carcinoma) and 54 women without evidence of the disease were prospectively studied to determine the relationship of genital infection to cervical neoplasia. Demographic and sexual data for patients and control subjects were collected, with standardized clinical and colposcopic evaluation by means of predefined diagnostic categories. Cultures from the cervix were examined for herpes simplex virus, cytomegalovirus, Chlamydia trachomatis, and Neisseria gonorrhoeae. Human papilloma virus infection was identified by characteristic changes of koilocytosis in cytologic or histopathologic specimen. Cultures from the vagina were evaluated for Gardnerella vaginalis, Trichomonas vaginalis, Ureaplasma urealyticum, Mycoplasma hominis, Candida albicans, and other yeasts. Separate Gram strains were prepared from endocervical secretions and from vaginal secretions. More lifetime sexual partners, larger area of transformation zone, evidence of human papilloma virus infection, and altered vaginal flora were observed in women with cervical intraepithelial neoplasia. The association of human papilloma virus infection and altered vaginal flora with cervical intraepithelial neoplasia was independent of sexual experience.