Cellular immunity to human basic myelin protein in women with dysplasia and carcinoma in situ of the cervix.

Sensitization to human myelin basic protein or encephalitogenic factor (EF), and antigen thought to be analogous to different human tumours, can be measured by the macrophage migration inhibition test (MMI). The MMI test was done on one occasion in 51 women with dysplasia and carcinoma in situ of the cervix; 20 women with non-malignant gynaecological conditions served as controls. Sensitization to EF was found in 71 per cent of women with carcinoma in situ and 42 per cent of women with dysplasia. None of the controls showed sensitization. Sensitization could not be related to histological evidence for cellular infiltration within the cervix.     

Studies on the prevalence and incidence rate of epithelial neoplasia of the uterine cervix by mass survey using mobile units

In this paper, we analyzed the results obtained in a mass survey using mobile units. The survey covered 276,846 women of whrom 78,018 (24.6%) were women who were being screened for the first time and the other 208,828 had been screened previously. 1) The total detection rate was 0.04% for invasive cancer, 0.03% for carcinoma in situ and 0.06% for severe dysplasia of the uterine cervix. The prevalence rate for 1,000 women was calculated as 0.40, 0.30 and 0.63 respectively. 2) The detection rate for invasive cancer, carcinoma in situ and severe dysplasia was 0.08%, 0.07% and 0.08% respectively for women who were being screened for the first time and 0.03%, 0.02% and 0.06% respectively for repeats. Through the latter results, the incidence rate for 100,000 women was calculated as 30 for invasive cancer, 20 for carcinoma in situ and 60 for severe dysplasia. 3) The detection rate for invasive cancer and severe dysplasia increased abruptly above 60 years and that for carcinoma in situ at 65 years old and over. 4) The detection rate for invasive cancer, carcinoma in situ and severe dysplasia in previously screened women showed little fluctuation by age group.     

Cervix cancer precursors in young offspring of low-income families.

The revolutionary changes in the mores and practices of adolescent sexuality have not as yet resulted in a significant increase in the rates of cervical cancer precursors in a study of 29,600 young women under age 21. The study represents women from families of low socioeconomic status. Over a 21-year period no cases of carcinoma in situ nor of invasive cervix cancer occurred. The dysplasia rate was low (0.9/1000), and when prerevolutionary and revolutionary periods were compared, there were no significant differences in the rates. Cryocautery was successful in ablating dysplasia, as was follow-up without treatment. An attempt will be made to continue to monitor these young women of the sexual revolution since the effects of their past and current participation might not be discernible for years to come.     

A study of abnormal cervical cytology in pregnant women

During the 4 year routine study of smears in 2,919 pregnant women, 33 cases of abnormals of the uterine cervix were detected (1.13%). The patients were followed with uterine cervical cytology and colposcopy and in case of need, sometimes punch biopsies were performed. The results of the cytologies, 33 cases with abnormalities were detected. There were 26 cases classified as class IIIa, 7 cases were class IIIb. All the cases underwent colposcopy. For the 17 cases that showed lesions by colposcopy, and punch biopsies were performed. The results of histologic examination were wide variety, five chronic cervicitis, one condyloma, one mild dysplasia, three moderate dysplasia, three severe dysplasia, three carcinoma in situ, and one microinvasive carcinoma. Only two cases were treated during pregnancy; one with condyloma underwent Laser vaporization and another with microinvasive carcinoma underwent LEEP conization. Other cases were given conservative treatment during pregnancy. Excluding one case for persistence smear class IIIa of histology condyloma, all the cases showed regression of dysplasia and carcinoma in situ with treatment after delivery. We conclude that lesions up to carcinoma in situ do not require intervention during pregnancy but microinvasive carcinoma is suspected, diagnostic LEEP conization is necessary, even during pregnancy.     

A study of abnormal cervical cytology in pregnant women

During the 4-year routing study of smears in 2,919 pregnant women, 33 cases of abnormalities of the uterine cervix were detected (1.13%). The patients were followed with uterine cervical cytology and colposcopy, and in case of need, sometimes punch biopsies were performed. As a result of the cytologies, 33 cases with abnormalities were detected. There were 26 cases classified as class IIIa and 7 cases were class IIIb. All cases underwent colposcopy. For the 17 cases that showed lesions by colposcopy, punch biopsies were performed. The results of histologic examination were wide: 5 chronic cervicitis, 1 condyloma, 1 mild dysplasia, 3 moderate dysplasia, 3 severe dysplasia, 3 carcinoma in situ, and 1 microinvasive carcinoma. Only two cases were treated during pregnancy, condyloma underwent Laser vaporization and microinvasive carcinoma underwent Loop electrosurgical excision procedure (LEEP) conization. Other cases were conservative treatment during pregnancy. Excluding one case for persistence smear class IIIa of histology condyloma, all the other cases with regression of dysplasia and carcinoma in situ with treatment after delivery. We conclude that lesions up to carcinoma in situ do not require intervention during pregnancy but microinvasive carcinoma is suspected, diagnostic LEEP conization is necessary, even during pregnancy.     

Behavior of mild cervical dysplasia during long-term follow-up

Five hundred and fifty-five women with cervical cytologically diagnosed mild cervical dysplasia were followed by cytology without major treatment. Biopsies were performed in 14% resulting in no significant influence on the outcome of the studied material. Regression to normal occurred in 62% (follow-up 39 months), progression to severe dysplasia/carcinoma in situ/invasive carcinoma in 16% (invasive carcinoma: two patients), and persistence of dysplasia in 22%. Life table analysis calculated the risk of progression of mild dysplasia to be 250 to 800/100,000 women/year. A comparison with the incidence of carcinoma in situ, four of 100,000 women/year, illustrates the yearly risk for a woman with mild dysplasia as 560 times greater than for a woman without cervical dysplasia to develop severe dysplasia/carcinoma in situ/invasive carcinoma.     

A study of cryosurgery for dysplasia and carcinoma in situ of the uterine cervix

We studied 22 patients with a histopathological diagnosis of severe dysplasia and 89 patients with a diagnosis of carcinoma in situ of the uterine cervix. Twenty patients (18 per cent) had negative cervical smears for four to six years after diagnosis by biopsy of the cervix. The 91 patients with persistently abnormal smears were treated by cryosurgery, using a double freeze technique with nitrous oxide. Seventy-four (86 per cent) had persistently normal cervical smears after one treatment and eight after a second treatment while nine patients required conization for recurrently abnormal cervical smears. The duration of follow-up was five or six years in 48 patients (53 per cent). In a subsidiary study, material was obtained for histological examination from 72 patients with normal smears by endocervical curettage and multiple biopsies of the cervix; 8 showed slight atypia and 2 had residual carcinoma in situ.     

Immunohistochemical demonstration of papillomavirus antigen in cervical dysplasia and vulvar condyloma

Biopsies from 30 cases of vulvar condyloma, 460 cases of cervical dysplasia, 30 cases of carcinoma in situ and 75 cases of invasive carcinoma of the cervix were screened for the presence of human papillomavirus (HPV) antigen by means of the peroxidase-antiperoxidase method. Positive reaction for HPV was detected in 14 cases of condyloma and 80 cases of dysplasia as a brown intranuclear precipitate in the superficial layer of the epithelium. None of the cases of carcinoma in situ and invasive cancer were positive for HPV. The mean age of the women with HPV-positive dysplasia was significantly lower than that of the women with HPV-negative dysplasia. Condylomatous dysplasia showed a significantly higher positive rate than did noncondylomatous dysplasia. Cases of condylomatous dysplasia with severe stromal inflammation were negative for HPV more frequently than those with mild stromal inflammation.     

The results of cryosurgical treatment in young women with cervical intra-epithelial neoplasia

A review is given of results from a 3-5-year follow-up of 105 young women treated with cryosurgery for a histopathologically verified dysplasia or carcinoma in situ of the uterine cervix. The recovery rate was 88%, with a slightly higher figure in the dysplasia group compared with that of carcinoma in situ. No invasive carcinoma was diagnosed and cases of treatment failure, all diagnosed within one year after cryosurgery, did not develop into a more severe form of neoplasia than previously. No recurrence has been noted so far and very few complications have been recorded. It is concluded that cryosurgery is an easy and effective method of treating cervical intra-epithelial neoplasia in young women. We stress, however, the importance of correct histopathological diagnosis prior to therapy and that after treatment the status of the patient must be checked with vaginal smears over a long period of time.     

Clinical studies on intravaginal administration of CDDP for dysplasia, carcinoma in situ and microinvasive carcinoma of the uterine cervix]

We attempted CDDP (cis-diaminedichloroplatinum) intravaginal administration by directly exposing the uterine cervix to CDDP in cases of dysplasia of the uterine cervix and cervical intraepithelial and micro-invasive carcinoma. Out of 12 patients, 7 had dysplasia of the uterine cervix (dysplasia was mild in 4, of an intermediate level in 1, 4 with mild dysplasia, 1 with and advanced in 2); 3 had carcinoma in situ, and 2 had microinvasive carcinoma. For CDDP intravaginal administration, a gauze tampon containing CDDP (5mg) was inserted into the vagina. CDDP administration was repeated daily for 10 days. The total dosage of CDDP administered was 50mg (new paragraph). During this period, vaginal cytologic examination was conducted and total plasma Pt content was determined daily for all. Following the completion of CDDP administration, the uterine cervices of those with dysplasia were histologically examined. For those with carcinoma in situ and microinvasive carcinoma, simple total hysterectomy was performed after intravaginal administration of CDDP to determine its therapeutic efficacy and the Pt concentration of the tissue; 1. In the 7 cases of dysplasia, dysplastic cell degeneration was observed 1-2 days after the start of intravaginal CDDP administration and these cells disappeared in all cases after its completion. 2. Sixteen histological sections of the resected cervical specimens from the 3 cases of carcinoma in situ showed complete disappearance of cancerous cells. 3. In the 2 cases of microinvasive carcinoma, no tumor cells were detected in one case; in the other case, tumor cells persisted in part of the resected specimen.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of cone biopsy in the management of carcinoma in situ of the cervix.

The success of conization in eradicating carcinoma in situ of the cervix was investigated. Between 1964 and 1973, 115 patients with carcinoma in situ of the cervix on cone biopsy were subsequently treated, within a maximum of 6 wk, by total hysterectomy. Residual significant disease (defined as carcinoma in situ or severe dysplasia) was found in the uterus of 51% of these patients. If in situ carcinoma was present at the surgical margins of resection in the cone biopsy, the incidence of residual significant disease in the uterus was 81%. Absence of in situ carcinoma at the surgical margin of the cone was associated with residual significant disease in the uterus in 31% of cases. This difference is statistically significant (P < 0.001). These cases were also analyzed with respect to age of patient, morphology of the carcinoma in situ, extent of involvement of the cone, and length of the resected endocervix. None of these variables was found to be significantly related to the incidence of residual uterine disease. It is concluded that study of resected cone margins for involvement is the only useful parameter in predicting the presence of residual disease in the uterus. However, since 31% of cones with negative margins were associated with residual disease in the uterus, hysterectomy is indicated if eradication of disease is the prime goal.     

Rapid Progression to Invasive Cervix Cancer in a Woman Infected with the Human Immunodeficiency Virus

Background: Previous studies have shown an increased risk of cervical dysplasia in women infected with human immunodeficiency virus (HIV), as well as an increased risk of progression to higher-grade lesions. It is not known whether the rate of progression is accelerated over that in immunocompetent women.Case: During September 1991, an HIV-positive woman underwent conization of the cervix showing carcinoma in situ. The surgical margins and endocervical curettings were negative for dysplasia. Papanicolaou smears 4 and 7 months after the conization also were negative. She then presented 33 months postconization with a stage Ib2 cervical carcinoma, which proved resistant to chemotherapy and pelvic radiation.Conclusion: Immunosuppression caused by HIV infection may cause a more rapid progression of cervical intraepithelial lesions to carcinoma.     

The cervix and hormonal contraception

This article reviews the histological effects of hormonal contraceptives on the cervix and assesses statistical studies examining the relationship between oral contraceptive (OC) usage and cancerous lesions of the cervix. The cervix acquires a pseudopregnant appearance under the influence of combined OCs. The Malpighian epithelium acquires a richly vascularized stroma characterized by accelerated maturation and the endocervical ectropion may be swollen, frequently with epidermoid metaplasia. Such changes increase with the duration of hormonal contraception and are more pronounced with combined than with sequential OCs. Among pathological changes that may occur are active adenomatous hyperplasia and epithelial abnormalities including dysplasia involving dyscaryotic cells with regular nuclei and no mitotic abnormality. Epithelial anomalies may present various histocytological features and are sometimes difficult to interpret. Epidemiologic study of the cervix is difficult because of the number of parameters to be considered: age at 1st intercourse, frequency of intercourse, number of partners, the formulation of the OC, and the variable duration of use which may have been interrupted by use of another method such as the IUD. Statistical studies have yielded contradictory results, with the earliest reports showing a higher incidence of dysplasia among women using OCs and most later studies showing a possible increased incidence of moderate dysplasia but no increased incidence of carcinoma in situ or invasive carcinoma. The recent study by Vessey et al. which compared 6838 parous OC users with 3154 parous IUD users over 10 years revealed invasive cancer in 13 women all of whom used OCs, with carcinomas in situ and dysplasias also more frequent in women using OCs. The duration of use was found to be a significant factor. Age and dates of marriage and 1st pregnancy were similar in subjects and controls, but no data were provided on age at 1st intercourse or number of partners. Regular cervical examinations and Pap tests should be performed for women using hormonal contraceptives to increase the probability of early detection of anomalies.     

The predictive value of LEEP specimens with involved margins for residual dysplasia

The objective of this study was to determine the percentage of loop electrosurgical excision procedure (LEEP) specimens with involved margins; also to determine factors associated with involved margins and the rate of residual dysplasia in the cervix post-LEEP. One hundred and sixty-nine women underwent LEEP excision of the cervix using standard techniques. Data concerning indications, complications, associated clinical factors, and histopathologic results were collected. Patients with involved specimen margins were examined for the presence of residual dysplasia 3 months post-LEEP. Thirty-one out of 131 (23.6%) specimens with histologically confirmed preinvasive disease had margins involved with dysplasia. Risk factors associated with margin involvement include referral Papanicolaou (Pap) smear result of high-grade squamous intra-epithelial lesion (SIL) (28/56) vs low-grade SIL (3/75) ( P < 0.0001), and human immunodeficiency virus (HIV) infection (3/3 with involved margins). Whether the LEEP was performed at initial visit (Look and LEEP) or following traditional colposcopy/ biopsy did not affect the involved margin rate. Only 18% (4/22) patients with involved margins had evidence of residual dysplasia, none with worse disease than the initial specimen. High-grade SIL on referral Pap, and HIV infection are risk factors for involved specimen margins. Additional treatment of patients with involved LEEP margins may be deferred, as more than 80% of patients will have no residual dysplasia at 3 months post procedure.     

Influence of norethynodrel and mestranol upon cervical dysplasia and carcinoma in situ

A 3-year progress investigation of the results of continuing serial cytologic, cytochemical, colposcopic, histologic, and clinical studies i nvolving 782 women is reported. These patients were selected from 60,00 0 women by a cytodiagnostic screening group before medication was given. The drug used was the steroid contraceptive Enovid, a combination of 9.85 mg norethynodrel with .15 mg mestranol. The usual daily dose of Enovid was 2, 5, or 10 mg orally. Tablets were taken in 20 doses from D ay 5 to Day 24 of the menstrual cycles. In some, continuous therapy was given at the same dosage for 60-240 days. Response was not related to dosage. Medication was begun after a cell-diagnosis was made. Frequent periodic examinations were made of cells scraped from the squamo-columnal junction of the cervix. This method was considered much more accurate than smears from the vaginal area. Some were followed for 3-4 years. No case was found in which a lesion progressed to a stage of infiltration. In the 654 women found to have normal cytology, Enovid therapy appeared to have exerted no unfavorable influence. Of the 66 women who had preexisting inflammatory lesions with precancerous tendencies, slight progression was noted in 2 (6%) and remission in 20 (30%). In 42 (64%) no change was found after Enovid medication. Of 60 patients having marked dysplasia of cells or with beginning carcinoma in situ, 3 (5%) showed remission, 15 (25%) showed fluctuation of findings, and 42 (70%) showed unaltered expected progression. Cytochemical investigations included continuing fluorescent microscopic studies to evaluate changing levels of DNA and RNA, glycogen studies, and micropolysaccharide evaluations. It is concluded that Enovid showed no carcinogenic influence even in preexisting premalignant dysplasia or carcinoma in situ of the cervix. However, periodic examinations with cervical cytologic studies are recommended for those under Enovid medication.     

Factors associated with positive margins in patients with cervical intraepithelial neoplasia grade 3 and postconization management

Objective

To evaluate the risk factors for positive margins in cervical intraepithelial neoplasia (CIN) grade 3 and the outcomes of postconization management.

Methods

A retrospective review of the records of 1113 women who underwent conization for CIN 3 between 2000 and 2008.

Results

Positive margins occurred in the following: 104 (10.7%) women with severe dysplasia versus 37 (26.2%) with carcinoma in situ; 32 (4.8%) treated with cold knife conization versus 109 (24.1%) treated with the loop electrosurgical excision procedure (LEEP); and 124 (11.6%) premenopausal versus 17 (35.4%) postmenopausal women. None of the women with severe dysplasia had invasive disease in the repeat excision specimen, whereas 3 (8.6%) women with carcinoma in situ had residual microinvasive carcinoma.

Conclusion

LEEP, carcinoma in situ, menopausal status, and larger area of lesion are risk factors for positive margins. For women with CIN 3 and positive margins, follow-up at an interval of 6 months or repeat excision are treatment options. However, when repeat excision is technically impossible, whether simple hysterectomy or radical surgery is a rational treatment option requires further investigation.     

Copper and zinc levels in serum from patients with abnormalities of the uterine cervix

Serum copper and zinc levels were determined by atomic absorption spectroscopy in 110 women with varying degrees of cervical dysplasia up to carcinoma-in-situ and in 9 women with invasive carcinoma of the cervix, and compared with levels in 21 women with no evidence of cervical dysplasia. The average serum copper and zinc levels in the control group were 1.25 mg/l and 1.02 mg/l (respectively). The mean serum copper level increased with dysplasia to 1.4 mg/l and with invasive carcinoma to 1.47 mg/l. The mean serum zinc levels were decreased in cervical intra-epithelial neoplasia (CIN) grade 1 to 0.81 mg/l and in invasive carcinoma to 0.73 mg/l. The copper:zinc ratios varied significantly between controls, patients with cervical dysplasia and patients with invasive carcinoma (p less than 0.01). Measurement of serum ceruloplasmin revealed no significant differences among the control group and the groups of patients.     

Pretreatment serum levels of C-reactive protein, alpha 1-antitrypsin, haptoglobin, alpha 1-acid glycoprotein and tissue polypeptide antigen in cervical carcinoma.

In order to evaluate the potentially additive information of some acute phase reactants to that provided by a general tumour marker, pretreatment concentrations of C-reactive protein, alpha 1-antitrypsin, haptoglobin, alpha 1-acid glycoprotein and tissue polypeptide antigen were determined in serum from healthy women, patients with dysplasia/or carcinoma in situ and patients with primary cervical carcinoma. Specificity varied from 95-100% and sensitivity from 16-29%. A correlation with clinical stage was found for all analytes except for alpha 1-antitrypsin. The latter was the most frequently elevated analyte in early Stages (11/43 in Stage Ib/IIa) and uniquely elevated in 7 cancer patients. Although tissue polypeptide antigen predominantly signaled in advanced stages, 3 women in early stages had elevated tissue polypeptide antigen levels. One of these women died and she was also the only woman with raised alpha 1-antitrypsin who died. It is discussed whether elevated tissue polypeptide levels might represent an unfavourable sign for the individual and if alpha 1-antitrypsin is a favourable sign in early stages of cervical carcinoma. C-reactive protein results were obscured in early stages of disease by the presence of intercurrent illness and the results were regarded as inconclusive. Haptoglobin and alpha 1-acid glycoprotein concentrations provided no additional information to serum alpha 1-antitrypsin levels. However, haptoglobin was elevated in 64% (36/56) of the women with dysplasia/carcinoma in situ of the cervix uteri.     

Clinical evaluation of contact Nd.YAG laser therapy of dysplasia and early cancer of the uterine cervix

For the past four years, cone and cone with cautery have been carried out by the contact Nd.YAG laser method after diagnosis with colpo.cervicoscopy in 174 cases of dysplasia and early cancer of the uterine cervix. The subjects were 82 patients with dysplasia, 75 patients with carcinoma in situ and 17 patients with microinvasive carcinoma. The cure rate based on the follow up for 6 to 50 months was 97.7%. There were 7 (4.1%) residual cases, 6 with residual mild dysplasia that required a follow up. Three cases with mild dysplasia disappeared during a follow up. In the remaining case, a semiradical hysterectomy was performed owing to Ib"occ" (8mm). Postoperative histological findings confirmed 76.2% of the preoperative findings; the rate of underdiagnosis was 23.8%. The rates of incomplete excision and underdiagnosis decreased in the cases where preoperative biopsy findings agreed with or overestimated cytologic and colpo.cervicoscopic findings. The results suggest that the laser cone is very useful as conservative therapy for early cervical neoplasia, and the cone specimen can be used to evaluate the success of the therapy and to improve future preoperative diagnosis.     

An epidemiologic study of cancer of the cervix, vagina, and vulva based on the Third National Cancer Survey in the United States.

Cases of invasive and in situ carcinoma of the lower female genital tract as reported in the Third National Cancer Survey in the United States were analyzed according to age, race, and geographic distribution. Results indicate that the incidence rates of in situ and invasive carcinoma of the cervix were greater in black than in white women, with a relative risk rate for black women of approximately two for both types of cervical carcinoma. For white women, the age-specific rates for invasive carcinoma of the cervix remained relatively constant after age 45, while for black women the age-specific rates for invasive carcinoma continued to increase after age 45. For both races, the patterns of age-specific incidence rates for in situ and invasive carcinoma of the cervix were not similar to those for carcinoma of the vagina or vulva. The pattern of age-specific incidence rates of adenocarcinoma of the cervix did not resemble those for in situ or invasive squamous cell carcinoma of the cervix. The rates for adenocarcinoma of the cervix demonstrated patterns similar to those for intraductal carcinoma of the breast. Results of the study are discussed in relationship to the field theory of carcinogenesis as developed for the lower female genital tract.