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PubMed1996

Follow-up of human papillomavirus (HPV) DNA and local anti-HPV antibodies in cytologically normal pregnant women.

The high level of progesterone during pregnancy may enhance the transcription and replication of genital human papillomaviruses (HPV) through the glucocorticoid/progesterone response element found in the long control region of the viral genome. In this study, cytologically and colposcopically healthy pregnant women were subjected to a follow-up examination. Samples from the uterine cervix were collected during early pregnancy (n = 39), in the third trimester (n = 31), and a few weeks after birth (n = 30). The presence of HPV DNA was detected by polymerase chain reaction (PCR), while local secretory anti-viral IgA antibodies were demonstrated by enzyme-linked immunosorbent assay using synthetic peptide antigens. Follow-up examination by PCR revealed HPV DNA persistence in 5 women. In 5 other cases, HPV positivity changed from negative to positive during the follow-up. There was 1 case which changed from positive to negative and 1 in which the HPV type changed during the study. Altogether, 12 of 39 women (31%) were shown to harbor HPV DNA at some time during follow-up. HPV DNA positivity increased from 18% during early pregnancy to 27% after birth (difference not significant). On the other hand, there was a significant rise in the level of local antibodies against HPV antigens (E2, E7, and L2) between samples collected in early pregnancy and those collected after birth (P < 0.0001). This may indicate the reactivation of genital HPV infections during late pregnancy.

Adolescent↗
PubMed2006

Longitudinal study of patients after surgical treatment for cervical lesions: detection of HPV DNA and prevalence of HPV-specific antibodies.

The principal aims of this study were to test whether persistence of human papillomavirus (HPV) DNA is predictive of recurrent disease in women after surgical treatment for cervical lesions, to distinguish between persistent and newly acquired HPV infection, and to observe the effect of surgical treatment on levels of HPV-specific antibodies. A group of 198 patients surgically treated for low-grade and high-grade squamous intraepithelial lesions and 35 age-matched controls were monitored for 18 months at 6-month intervals. The presence of HPV DNA in cervical smears was detected by means of consensus polymerase chain reaction, and serum levels of HPV-specific antibodies to HPV types 16, 18, 31, 33, and 45 were measured. In ten patients positive for HPV type 16 in consecutive samples, the HPV 16 variants were identified using a polymerase chain reaction specific for the long control region. Data regarding demographics, risk factors for cervical cancer, and risks related to HPV exposure were collected through a patient questionnaire. Subjects persistently positive for HPV DNA were more likely to present with cytological and/or colposcopical abnormalities. A higher reactivity to HPV-specific antibodies was observed in these women at the 18-month follow-up visit. All ten patients with HPV 16 infection detected in consecutive samples showed persistence of either the same prototype or the same variant during the follow-up period. Risky sexual behavior and smoking were more common in patients than in controls. Persistent HPV infection as demonstrated by both HPV DNA detection and antibody detection appears to be a risk factor for the recurrence of pathological findings in women after surgery. An individually based approach to surgical treatment is an important factor in the outcome of disease at follow-up.

Adolescent↗
PubMed2006

The systemic absorption of etoposide after intravaginal administration in patients with cervical intraepithelial lesions associated with human papillomavirus infection.

PURPOSE: The purpose of this study was to determine the systemic absorption and the release of etoposide in cervical tissue administered via a vaginal ovule to women diagnosed with cervical intraepithelial lesions associated with human papillomavirus (HPV). METHODS: Fifteen women with low- and high-grade intraepithelial neoplasia confirmed by colposcopic test received a 50-mg intravaginal etoposide dose three times a week for 3 weeks. At the end of the study period, paralleled with the last ovule administered, blood samples were collected over a period of 24 h, and in situ cervical samples were obtained at 3 and 10 h after drug administration. Etoposide concentrations were determined in plasma and in in situ cervical samples using the high-performance liquid chromatography method with electrochemical detection. RESULTS: Pharmacokinetic analyses of plasma data indicated low or lack of systemic exposure of etoposide after the vaginal administration. Nevertheless, high concentrations of etoposide were found in all in situ cervical samples, indicating that etoposide could be released from its pharmaceutical formulation. CONCLUSIONS: The results of the study suggest that the etoposide administered as intravaginal ovule is safe and tolerable and apparently could be a suitable option in patients with cervical intraepithelial neoplasia. Clinical results and the true impact on HPV infection and evolution of dysplasia need to be confirmed.

Absorption↗
PubMed1976

Outpatient evaluation of patients with atypical Papanicolaou smears: contribution of endocervical curettage.

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.

Biopsy↗
PubMed1976

Abnormal cervical cytology in the teen-ager: a continuing problem.

Abnormal cervical cytology is being discovered in an alarming number of sexually active teen-agers. Over an 18 month period, cytology consistent with mild dysplasia or worse was noted in 188 of 2,655 teen-agers screened. This represents a rate of 70.8 per thousand. Colposcopically directed biopsies in 65 patients revealed 15 cases of severe dysplasia-carcinoma in situ. Cryosurgery was the principle method of treatment and, combined with colposcopy, is a safe and effective means of managing these patients.

Adolescent↗
PubMed1978

Cryosurgery for the treatment of cervical intraepithelial neoplasia.

Cryosurgery was used to treat 208 patients with cervical intraepithelial neoplasia. These patients were referred to our Colposcopy Clinic for investigation of an abnormal Papanicolaou smear. Prior to treatment a colposcopically directed biopsy was taken in all cases. The regrigerant used for cryosurgery was nitrous oxide. Included in the 208 patients were 57 with mild dysplasia, 76 with moderate dysplasia, 44 with severe dysplasia and 31 with carcinoma in situ. The cure rates were 100 per cent for patients with mild dysplasia, 95 per cent for those with moderate dysplasia, 96 per cent for those with severe dysplasia and 91 per cent for those with carcinoma in situ. Cryosurgery is an effective method of treating cervical intraepithelial neoplasia, with cures obtained in 199 of 208 patients in this study.

Adolescent↗
PubMed1978

Role of endocervical curettage in colposcopy.

A series of 1,850 patients with atypical Papanicolaou smears referred to the Colposcopy Clinic at Cook County Hospital were evaluated. There were 2,000 colposcopic examinations with or without directed biopsy and 495 endocervical curettements. Records of 126 patients who had definitive diagnoses were reviewed. Of 126 patients, 41 had diagnostic conization following colposcopy-directed biopsy and endocervical curettage; 85 had only colposcopy-directed biopsy and endocervical curettage. There were two instances in which an invasive cancer was missed prior to therapy, one in the group of 41 patients (incidence of 2.4 per cent), the other in the group of 85 patients (incidence of 1.1 per cent). Cone biopsy contributed very little to establishing the diagnosis of invasive cancer following colposcopy-directed biopsy and endocervical curettage. Safety measures for endocervical curettage performed during pregnancy are presented. The management of patients evaluated by colposcopy-directed biopsy and endocervical curettement requires careful correlation of histo- and cytopathology.

Biopsy↗
PubMed1980

High-power--density carbon dioxide laser therapy for early cervical neoplasia.

A total of 115 women with various grades of CIN were treated with high-power--density, continuous time mode CO2 laser beams. During the 2-year follow-up period, residual tumor was noted in 4.34% of the treated cases. Detailed observations of the rapid healing of tissues after laser exposure were carried out in 50 women who were colposcoped every other day for 4 weeks. The CO2 laser is an acceptable instrument for use in treating early gynecologic malignancy, with its principal advantage being the precision with which it destroys tissue.

Adolescent↗
PubMed1981

The effect of condom use on squamous cell cervical intraepithelial neoplasia.

Between January 1, 1968, and July 1, 1980, 377 of a total 412 patients with biopsy-proven cervical intraepithelial neoplasia (CIN) were seen in the private office of the authors and followed for more than 6 months after biopsy and the start of treatment. Thirty-five patients were lost to follow-up. Ninety-one were treated primarily by hysterectomy. The 286 patients in whom childbearing function was to be preserved were instructed, as soon as the diagnosis of CIN was confirmed, to use a mechanical barrier (the condom) throughout intercourse. In addition to the use of the condom, 40 of the 286 underwent surgical conization and 107 underwent cryosurgery. All of these 147 patients eventually showed cytologic and colposcopic regression of the disease. One hundred and thirty-nine patients were treated with the condom alone. One hundred and thirty-six of the 139 showed complete regression of the disease. Eighteen (6.2%) of the 286 patients had late recurrences of the disease; 12 of these experienced regression again with the resumption of the use of the condom. No patients showed progression of the disease while using the condom. All grades of CIN proved to be reversible. It is recommended that a mechanical barrier at intercourse be added to any program for conservative treatment of CIN.

Adult↗
PubMed1982

Outpatient therapy: success and failure with dysplasia and carcinoma in situ.

Between 1971 and 1980, 385 patients with colposcopic biopsy-proved cervical intraepithelial neoplasia were treated by either the colposcopist or the referring physician by means of cryosurgery, electrocautery, or biopsy excision. All were observed for a minimum of 1 year, 220 between 1 and 2 years, 50 between 3 and 4 years, and 23 for 4 or more years. Therapy failed in 29 in the first year ("failures" proved by tissue examination). The failure rate among the 35 patients with carcinoma in situ was 20%, a rate significantly higher than that seen in 108 patients with severe dysplasia (7 or 6.5%) or in mild and moderate dysplasia (4.4% and 8.5%, respectively). There were 10 "recurrences" seen among those observed for more than 1 year after treatment. In eight instances the histologic severity of the recurrence was more severe than that of the original lesion. The comparative efficacy of cryosurgery and electrocautery and the success and failure rates for the colposcopists and other therapists who had not viewed the lesions prior to therapy are examined.

Adolescent↗
PubMed1982

Diagnostic significance and sequelae of cone biopsy.

All cone biopsies from our institution over a 10-year period were reviewed. Two hundred seventy-one patients underwent 274 procedures. Preoperative colposcopic evaluation markedly reduced the proportion of patients with residual cervical epithelial neoplasia (CIN). No patient in our series required conization for diagnosis of frankly invasive carcinoma. Following colposcopy and conization, 8% of patients had disease extending to the surgical margins; eight of 11 such patients (72%) with adequate follow-up had no further CIN. Colposcopy and cytology underestimate the final pathologic diagnosis in many patients with incomplete visibility of the transformation zone, so conization is mandatory in this circumstance. Conization in pregnancy was associated with increased hemorrhage; colposcopy has reduced the need for this operation in gravid patients.

Biopsy↗
PubMed1984

Laser cylindrical excision to replace conization.

This report describes the procedures and results of two techniques, which were developed by the senior author (V.C.W.), for eliminating cervical intraepithelial neoplasia involving, to some degree, the endocervical canal. These are excision by carbon dioxide laser of a tall cylinder of tissue for pure endocervical lesions and shallow excision of a similar specimen followed by peripheral vaporization. In 364 consecutive referred cases one of these two procedures was performed. A total of 15.9% of patients required attention for bleeding; most cases were managed in the clinic. Near-normal tissue mass and a squamocolumnar junction at the os were observed during 3 to 60 months of follow-up. In 95.9% of cases, over half of which were grade 3 cervical intraepithelial neoplasia, normal cytologic and colposcopic findings were demonstrated after one laser procedure. A repeat laser procedure was used to eliminate persistent disease identified at 3 or 6 months. Five hysterectomies were performed. These procedures appear to be therapeutically effective, appear to preserve organ function, and allow regeneration of cervical mass.

Adenocarcinoma↗
PubMed1984

Treatment of cervical intraepithelial neoplasia with electrocautery: report of 426 cases.

Four hundred twenty-six patients with colposcopically directed, biopsy-proved, mild, moderate, or marked dysplasia or carcinoma in situ of the cervix were treated with outpatient electrocauterization, from 1973 to mid- 1982. Of these, 413 were available for follow-up between 3 and 6 months. The initial cure rate was 85.95%, and the cure rate when a second treatment for initial failures was included was 96.6%. These patients have been followed for 1 to 5 years, and the annual follow-up rate has ranged from 65% to 80%. Recurrences were few, but did occur as late as 3 years after treatment.

Carcinoma in Situ↗
PubMed1984

Carcinoma in situ of the vagina.

A review was made of 136 cases of carcinoma in situ of the vagina seen over a 30-year period, 1953 to 1982. The patients ranged in age from 17 to 77 years, with a mean age of 55 years. One hundred sixteen patients (85%) presented with an abnormal Papanicolaou smear. Colposcopically directed biopsies were used for diagnosis in 62% of the patients. The upper one third of the vagina was the most common site of disease, with 54% of patients having unifocal lesions. A previous hysterectomy had been performed in 71% of patients, 35% of whom had undergone operation for benign disease. A concomitant, subsequent, or prior neoplasm of the lower genital tract or pelvis was noted in 109 patients. Surgical intervention in the form of either wide local excision or partial or total vaginectomy was the most frequently used method of treatment. Radiotherapy, usually in the form of a vaginal mold, was the second most commonly used method of treatment, and it was used in 27 patients. Radiotherapy and more extensive surgical treatment methods gave the best results. Four patients subsequently developed invasive carcinoma of the vagina.

Adolescent↗
PubMed1985

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.

Adolescent↗
PubMed1985

Plasma vitamin C and uterine cervical dysplasia.

Plasma concentrations of vitamin C were determined in a case-control study of women (n = 80) who had sought a Papanicolaou test in the Bronx Municipal Hospital Center. Controls (n = 34) were women having negative cytologic tests, negative colposcopic findings, and no known gynecologic dysfunction. Cases (n = 46) were defined as women who had either one positive or two consecutive suspicious Papanicolaou smears in a 12-month period. The mean concentration of vitamin C in the plasma was significantly lower in the cases than in the controls (0.36 versus 0.75 mg/dl, p less than 0.0001). Cases were further stratified according to the histopathologic diagnosis. The data direct attention to a possible etiologic association of vitamin C in human cervical epithelial abnormalities. A clinical trial with vitamin C intervention is suggested.

Adult↗
PubMed1987

The value of endocervical curettage in the management of the patient with abnormal cervical cytologic findings.

Patients with adequate colposcopic examinations and dysplasia on the endocervical curettage specimen usually undergo further diagnostic evaluation. This study evaluated 712 patients and found the frequency of positive endocervical curettage specimens to be 17.6%. Cervical conization or hysterectomy specimens were examined in 66 cases with a positive endocervical curettage. Of these, 69.7% had histologic evidence of discontinuous dysplasia in the endocervical canal. The endocervical curettage specimens were grouped by the percentage of endocervical epithelium that was dysplastic: group 1, less than 10%; group 2, 10% to 50%; group 3, greater than 50%. Confirmed histologic endocervical involvement was 80%, 56%, and 60%, respectively. The involvement of the endocervical canal also increased with increasing grade of cervical intraepithelial neoplasia. Of the 66 cases examined with positive endocervical curettage specimens, 62.1% had grade 3 cervical intraepithelial neoplasia on the ectocervix. Seven patients had positive endocervical margins, with six of these occurring in grade 3 cervical intraepithelial neoplasia lesions. Two unsuspected cases of cervical malignancy were identified by endocervical curettage.

Carcinoma↗
PubMed1987

Sexually transmitted papillomaviral infections. I. The anatomic distribution and pathologic grade of neoplastic lesions associated with different viral types.

Multiple colposcopic biopsy specimens were collected from 160 women, with sampling of principal cervical and vulvar lesions as well as secondary areas of either minor acetowhitening or normal epithelium. Papillomaviral deoxyribonucleic acid was detected by Southern blot hybridization in 197 (90%) of the 218 principal biopsy specimens and 93 (46%) of 198 secondary biopsy specimens. Although different papillomaviruses were found at different sites in 31 women, only six of 416 specimens contained multiple types within the same sample. Specific viral types were associated with specific disease patterns. Only one of 80 type 6 or 11 infections had a diagnosis greater than cervical intraepithelial neoplasia, grade 2. In contrast, 42 of 48 (90%) biopsy specimens of cervical intraepithelial neoplasia, grade 3, or invasive cancer contained type 16, 18, or 31. Nonetheless, 12 of 124 (10%) cases of condyloma and cervical intraepithelial neoplasia, grade 1, were associated with types 16, 18, and 31 infections. Of 58 women with multicentric disease, 46 had positive hybridizations for both cervical and vulvar lesions (32 showing the same type in both samples and 14 showing different viruses). Differing patterns of papillomavirus-induced disease arise partly from the predilection of specific viral types for certain anatomic sites and partly through variations in host response. Detection of viral deoxyribonucleic acid in 46% of the secondary biopsy specimens suggests that disease expression may represent focal breakdown of host surveillance within a field of latent papillomaviral infection.

Biopsy↗