Showing papers on "Cervix published in 1994"

Molecular pathogenesis of cancer of the cervix and its causation by specific human papillomavirus types.

Abstract: Less than 10 years after publication of the hypothesis of a papillomavirus etiology of cancer of the cervix (zur Hausen 1975, 1976, 1977), the DNAs of the first cervical cancer-associated human papillomavirus (HPV) types were cloned and characterized. These DNAs are regularly and frequently found in biopsies obtained from cervical cancer patients throughout the world (Durst et al. 1983; Boshart et al. 1984).

In vivo diagnosis of cervical intraepithelial neoplasia using 337-nm-excited laser-induced fluorescence

Abstract: Laser-induced fluorescence at 337-nm excitation was used in vivo to differentiate neoplastic [cervical intraepithelial neoplasia (CIN)], nonneoplastic abnormal (inflammation and human papilloma viral infection), and normal cervical tissues. A colposcope (low-magnification microscope used to view the cervix with reflected light) was used to identify 66 normal and 49 abnormal (5 inflammation, 21 human papilloma virus infection, and 23 CIN) sites on the cervix in 28 patients. These sites were then interrogated spectroscopically. A two-stage algorithm was developed to diagnose CIN. The first stage differentiated histologically abnormal tissues from colposcopically normal tissues with a sensitivity, specificity, and positive predictive value of 92%, 90%, and 88%, respectively. The second stage differentiated preneoplastic and neoplastic tissues from nonneoplastic abnormal tissues with a sensitivity, specificity, and positive predictive value of 87%, 73%, and 74%, respectively. Spectroscopic differences were consistent with a decrease in the absolute contribution of collagen fluorescence, an increase in the absolute contribution of oxyhemoglobin attenuation, and an increase in the relative contribution of reduced nicotinamide dinucleotide phosphate [NAD(P)H] fluorescence as tissue progresses from normal to abnormal in the same patient. These results suggest that in vivo fluorescence spectroscopy of the cervix can be used to diagnose CIN at colposcopy.

Enhancement of Regression of Cervical Intraepithelial Neoplasia II (Moderate Dysplasia) With Topically Applied All-trans-Retinoic Acid: a Randomized Trial

Abstract: Author(s): Meyskens, FL; Surwit, E; Moon, TE; Childers, JM; Davis, JR; Dorr, RT; Johnson, CS; Alberts, DS | Abstract: BackgroundRetinoids enhance differentiation of most epithelial tissues. Epidemiologic studies have shown an inverse relationship between dietary intake or serum levels of vitamin A and the development of cervical dysplasia and/or cervical cancer. Pilot and phase I investigations demonstrated the feasibility of the local delivery of all-trans-retinoic acid (RA) to the cervix using a collagen sponge insert and cervical cap. A phase II trial produced a clinical complete response rate of 50%.PurposeThis randomized phase III trial was designed to determine whether topically applied RA reversed moderate cervical intraepithelial neoplasia (CIN) II or severe CIN.MethodsAnalyses were based on 301 women with CIN (moderate dysplasia, 151 women; severe dysplasia, 150 women), evaluated by serial colposcopy, Papanicolaou cytology, and cervical biopsy. Cervical caps with sponges containing either 1.0 mL of 0.372% beta-trans-RA or a placebo were inserted daily for 4 days when women entered the trial, and for 2 days at months 3 and 6. Patients receiving treatment and those receiving placebo were similar with respect to age, ethnicity, birth-control methods, histologic features of the endocervical biopsy specimen and koilocytotic atypia, and percentage of involvement of the cervix at study. Treatment effects were compared using Fisher's exact test and logistic regression methods. Side effects were recorded, and differences were compared using Fisher's exact test.ResultsRA increased the complete histologic regression rate of CIN II from 27% in the placebo group to 43% in the retinoic acid treatment group (P = .041). No treatment difference between the two arms was evident in the severe dysplasia group. More vaginal and vulvar side effects were seen in the patients receiving RA, but these effects were mild and reversible.ConclusionsA short course of locally applied RA can reverse CIN II, but not more advanced dysplasia, with acceptable local side effects.ImplicationsA derivative of vitamin A can reverse or suppress an epithelial preneoplasia, lending further support to the notion that chemoprevention of human cancer is feasible.

Precancerous Lesions of the Cervix

Abstract: The histopathological classification of a disease should reflect both current concepts of its pathogenesis as well as its clinical behavior. Over the last 50 years our understanding of the pathobiology and behavior of cervical cancer precursors has evolved considerably. As a result, the terminology used to classify preinvasive lesions of the cervix has frequently changed.40 Although these changes in nomenclature and the resulting lack of a uniform terminology have been an ongoing source of confusion to both gynecologists and pathologists, each change has actually reduced the number of specific pathological categories and has made clinical decision-making more straightforward.

Is Trichomonas vaginalis a Cause of Cervical Neoplasia? Results from a Combined Analysis of 24 Studies

Abstract: The authors conducted this combined analysis of available data from studies with information on this issue to clarify the association between Trichomonas vaginalis infection and cervical neoplasia. They performed MEDLINE searches (1966-1993) using the key words and phrases trichomonas vaginitis and neoplasms cervix for articles published in English and searched citations of the articles obtained from MEDLINE. A total of 24 articles (two cohort studies and 22 case-control) were included in this data analysis. In the analysis the studies were evaluated for heterogeneity using Breslow-Day tests for homogeneity of the odds ratios and of rate ratios. If the odds ratios from studies are heterogeneous it is not appropriate to combine them using the Mantel-Haenszel method. Also publication bias was evaluated by assessing the association between the observed effect size and the variance of the effect size using a rank correlation test. The combined summary relative risk for the two cohort studies was 1.93 (95% confidence interval: 1.22-2.65) indicating an approximate doubling of the risk of cervical neoplasia in the presence of T. vaginalis infection. The attributable risks among exposed subjects and among the source population were 47.4% and 2.1% respectively. Results of the 22 retrospective studies were much less consistent. However most of them demonstrated a significant positive association. This combined analysis suggests that there is an association between T. vaginalis and the risk of cervical neoplasia but that such infections account for only 2% of cervical neoplasia. (authors)

Small cell carcinoma of the cervix. A clinicopathologic study of 26 patients

Abstract: Background Small cell carcinoma of the cervix is a rare and aggressive tumor. Most gynecologic oncology centers have little experience with this tumor, and only small series have been published. Methods Twenty-six patients with small cell carcinoma of the uterine cervix were treated at the Norwegian Radium Hospital. Clinical data, immunohistochemical characteristics, and infection with human papillomavirus were studied. Results Twelve tumors were of oat cell type and 14 of intermediate cell type. Twelve tumors were associated with other forms of carcinoma: squamous cell carcinoma (6 tumors), adenocarcinoma (5 tumors), and adenocarcinoma in situ (1 tumor). Neuroendocrine differentiation was expressed in 79% of the tumors. Human papillomavirus (HPV)-18 was detected in 40% of the tumors and HPV-16 in 28%. Fifteen patients had Stage I disease, 7 had Stage II, 2 had Stage III, and 3 had Stage IV. Fourteen patients with Stage I and II disease underwent radical hysterectomy with pelvic lymph node dissection. In four, the operation was preceded by intracavitary radiation treatment. The patients with Stage II, III, and IV disease were treated with a combination of intracavitary radium, external beam radiation therapy, and chemotherapy. The 5-year survival rate was 14%. Four patients are alive, one with recurrent disease 50 months after diagnosis. Three patients free of disease have been followed up 26, 54, and 101 months, respectively. Conclusions Small cell carcinoma of the cervix is an aggressive tumor with a propensity for rapid recurrence; it is associated with high mortality.

Association Between Cervical Inflammation And Cervical Shedding Of Human Immunodeficiency Virus DNA

Abstract: This study evaluated the prevalence and correlates of cervical human immunodeficiency virus (HIV) DNA in a group of 92 HIV-seropositive Kenyan prostitutes. HIV seropositivity was confirmed by enzyme-linked immunosorbent assay and Western blot. HIV DNA amplification was performed via polymerase chain reaction. Data were evaluated using standard statistical methods. Risk factor effects were assessed by multivariate logistic regression. Cervical HIV DNA was found in 36 women (39%) during their initial visit. There was a significant correlation between cervical HIV and cervical inflammation (odds ratio [OR] 7.2; 95% confidence interval [CI] 2.1-24.6). The adjusted OR for the association between cervical HIV DNA and cervical inflammation was 8.7 (95% CI 2.0-37.2).

Screening for cervical intraepithelial neoplasia in north east Scotland shows fall in incidence and mortality from invasive cancer with concomitant rise in preinvasive disease.

Abstract: Objective : To assess the effect of screening for cervical intraepithelial neoplasia on the incidence of and mortality from invasive squamous cell carcinoma of cervix in north east Scotland and to discover why cases of invasive cancer still occur. Design : (a) Analysis of data on cases of cervical intraepithelial neoplasia obtained from the cytology data bank; (b) analysis of data on 612 women presenting with invasive squamous cancer during 1968-91, obtained from cancer registry and hospital records; (c) analysis of death rates obtained from the registrar general9s (Scotland), and annual reports, the Information Services Division of the Home and Health Department (Scotland), and local records for 1974-91; (d) case-control studies on 282 cases of invasive cancer and 108 deaths which occurred in 1982-91. Cases were matched with two controls both for age and for having a negative smear test result at the time of presentation of the case. Setting - North east Scotland (Grampian region, Orkney, and Shetland). Subjects - Women (n - 306608) who had had cervical smear tests between 1960 and 1991. Results : There had been substantial increase in cases of cervical intraepithelial neoplasia grade III since 1982. The incidence of invasive cancer has fallen since the start of screening in 1960, the fall occuring mainly in the well screened age group 40-69 years. There was a rise in women aged under 40 and over 70. Women with invasive disease seen between 1982 and 1991 mostly presented at stage I. Of these, half were unscreened, one third were poorly screened, 11% were found in retrospect to have had abnormal cells, 3% had recurrence of disease after treamtne for cervical intraepithelial neoplasia grade III, and 3% were lost to follow up. Death rates had fallen, most noticeably in women aged 45-64, who had had the opportunity to be screened and rescreened. There was a disturbing rise in deaths among women under 45. Most deaths (65%) occurred in unscreened women. Case-control studies showed that the longer the time and absence of a smear test before presentation the higher was the risk of invasive cancer and of death. Conclusions : Screening has been effective in reducising the incidence of the mortality from cervical cancer in north east Scotland. Most cases and deaths occurred in unscreened women or in those who had had few smears at long intervals. An increase in cases of cervical intraepithelial neoplasia grade III in women screened for the first time occurred during 1982-91.

Cancer Prevention in Primary Care: Screening for cervical cancer

Abstract: Cervical screening has been shown to be effective in several countries, although not by means of randomised controlled trials. A screening programme has been in operation in the United Kingdom since 1964, but it has, in the past, been beset with problems of organisation, accountability, and commitment. The introduction in 1988 of a systematic call and recall system and the setting up of an NHS cervical screening programme national coordinating network has brought a greater sense of coherence. Coverage of the target population in England between 1989-90 and 1992-3 increased from 61% to 83%, and there is a strong indication that cervical screening is now beginning to reach those most at risk - namely, older women from lower social classes. Primary care is central to the overall success of the cervical screening programme. General practitioners are in a unique position to invite women for a smear test, to take smears, to ensure that abnormal smear test results are followed up, and to check on reasons for non-attendance. Numerous studies have looked at the involvement of general practice in cervical screening, identifying many ways in which the programme can be improved. Many practices are now running well organised and effective programmes. * This is the seventh in a series of articles looking at how cancer can be prevented in general practice In England and Wales during 1988, 4467 new cases of invasive carcinoma of the cervix were registered (4940 in the United Kingdom as a whole), making it the eighth commonest cancer in women. Although only 15.5% of cases occur in women under 35, it is the most common cancer in this age group, accounting for 25% of all new cancers. Since the early 1970s there has been a significant increase in the incidence of both carcinoma in situ and invasive …

Epidemiology of cervical human papillomavirus infections.

Abstract: This update will summarize recent advances regarding the epidemiology of human papillomavirus (HPV) infections of the cervix. Readers interested in earlier, more comprehensive reviews are referred to two excellent summaries by Koutsky et al. (1988) and Schneider and Koutsky (1992). This update will be restricted to cervical HPV infection and will not include recent advances in the epidemiology of cutaneous HPV types or genital types infecting sites other than the cervix (e.g., aerodigestive tract).

Functions of human papillomavirus proteins.

Abstract: Cervical cancer is the second leading cause of deaths from cancer among women worldwide with approximately 500 000 deaths annually. Epidemiologic studies have implicated a sexually transmitted agent as a cause of cervical cancer, and molecular virology studies over the past 10 years have established a strong association between specific human papillomavirus (HPV) types and certain anogenital carcinomas, including cervical cancer (reviewed in zur Hausen and Schneider 1987). Over 65 different HPV types have now been described, and each is associated with a specific clinical entity (DeVilliers 1989). Approximately 20 or 25 HPVs have been associated with anogenital lesions; these HPVs have been further classified as either “low-risk” or “high-risk” types based on the preneoplastic character of the clinical lesions with which they are associated. Low-risk HPVs such as HPV-6 and HPV-11 are generally associated with venereal warts or condyloma acuminata which only rarely progress to malignancy. The high-risk HPVs include HPV-16 and HPV-18 and these are associated with squamous intraepithelial neoplasias which are potentially precancerous. In the cervix, they are associated with cervical intraepithelial neoplasia, or CIN. These CIN lesions are considered preneoplastic in that a small percentage of high-grade CIN lesions will progress to cervical cancer. Approximately 70% of human cervical cancers contain either HPV-16 or HPV-18 DNA (zur Hausen and Schneider 1987). Indeed, HPV-16 and HPV-18 DNA were originally isolated from human cervical carcinoma tissues (Durst et al. 1983; Boshart et al. 1984). Other high-risk HPVs, including types 31, 33, 35, 39, 45, 51, and 52, have subsequently been identified and have also been associated with CIN lesions and with invasive cervical carcinomas. All together, approximately 85% of cervical cancers can be shown to contain DNA of one of the high-risk HPV types (Riou et al. 1990).

Sexually Transmitted Diseases and Other Risk Factors for Cervical Dysplasia Among Southwestern Hispanic and Non-Hispanic White Women

Abstract: Objective. —To assess risk factors for high-grade cervical dysplasia among southwestern Hispanic and non-Hispanic white women. Design. —Clinic-based case-control study. Setting. —University-affiliated gynecology clinics. Subjects. —Cases were Hispanic and non-Hispanic white women with biopsy-proven high-grade cervical dysplasia (n=201). Controls were Hispanic and non-Hispanic white women from the same clinics with normal cervical epithelium (n=337). Methods. —Study design included interviews focused on histories of sexually transmitted diseases, sexual behavior, reproductive histories, hygienic practices, contraceptive use, cigarette smoking, and diet. Laboratory studies included bacterial and protozoal cultures of the cervix; hybridization tests to identify human papillomavirus (HPV) genome with commercial (ViraPap and ViraType) and polymerase chain reaction—based assays; and serum antibody tests for herpes simplex virus,Chlamydia trachomatis, syphilis, hepatitis B, and hepatitis C. Results. —For both ethnic groups combined, after adjustment for ethnicity, age, and sexual behavior, the strongest risks for cervical dysplasia were associated with cervical HPV infection as identified by ViraPap (odds ratio [OR], 12.8; 95% confidence interval [Cl], 8.2 to 20.0) or with polymerase chain reaction (OR, 20.8; 95% Cl, 10.8 to 40.2). Other factors associated with dysplasia included cigarette smoking at the time of diagnosis (OR, 1.8; 95% Cl, 1.2 to 2.8); low income (OR, 2.2; 95% Cl, 1.2 to 4.0); low educational level (OR, 6.2; 95% Cl, 3.4 to 11.1); history of any sexually transmitted disease (OR, 1.9; 95% Cl, 1.3 to 2.7); and seroprevalence of antibodies to hepatitis B (OR, 1.8; 95% Cl, 0.9 to 3.5). For Hispanic women, HPV 16/18 identified by ViraType was strongly associated with cervical dysplasia (OR, 171.0; 95% Cl, 22.8 to 1280.5). Antibodies to herpes simplex virus type 2 were not associated with dysplasia in Hispanic women but were significantly associated with dysplasia among non-Hispanic whites. Risks associated with cigarette smoking also varied by ethnic group. Conclusions. —The strongest risk factor associated with high-grade cervical dysplasia among clinic attendees was HPV infection. Although most of the risk factors we examined showed similar associations for dysplasia for both ethnic groups, our data suggest that several different risk factors may be relevant to the development of cervical dysplasia in Hispanics compared with non-Hispanic whites who attend the same clinics. (JAMA. 1994;271:1181-1188)

Association between HLA-DQB1 alleles and risk for cervical cancer in African-American women.

Abstract: Squamous-cell carcinoma of the cervix and its precursor lesions are associated with human papillomavirus (HPV) infection. Epidemiological studies indicate that HPV infection in itself is not sufficient for cervical-cancer induction, suggesting that other factors contribute to carcinogenesis. We have investigated the potential role of host genetic background as one such factor. We screened a series of squamous-cell carcinomas of the cervix for HLA-class-II DQB1* alleles by the polymerase chain reaction and site-specific oligonucleotide probe hybridization and for HPV type from African-American women using a local, ethnically matched control panel. Statistically significant associations for increase in relative risk for cervical cancer were seen for DQB1*0303 and DQB1*0604. DQB1*0201 and the heterozygote DQB1*0301/*0501 showed a decrease in relative risk for cervical cancer. HPV typing revealed no association between virus type and DQB1 alleles. Our results confirm other studies showing an increase in relative risk for cervical cancer associated with HLA-DQ3 alleles in Caucasians.

Survival trend after invasive cervical cancer diagnosis in Sweden before and after cytologic screening. 1960-1984.

Abstract: Background. Cytologic screening can reduce mortality from cervical cancer by detection and removal of premalignant lesions. Conceivably, mortality is further reduced because more women with invasive disease are diagnosed at an earlier. curable stage. This hypothesis can be assessed in Sweden, where population-based screening programs were introduced successively over about a decade starting in 1964. Methods. Record linkages permitted complete follow-up through 1986 of all 17,377 patients with invasive cervical cancer diagnosed in Sweden from 1960 through 1984. We analyzed relative survival rates that describe the survival of patients after elimination of the effects of causes of death other than cancer of the cervix. Results. Prognosis improved substantially in patients younger than age 50 years at diagnosis; from 1960–1964 to 1980–1984, the 5-year relative survival rate increased from 69.8% to 88.8% at age 20–29 years, from 71.7% to 85.5% at age 30–39 years, and from 68.6% to 77.9% at age 40–49 years. The excess mortality was thus reduced by more than half in patients diagnosed when younger than 40 years. In contrast, only slight or no improvement was noted in those diagnosed at older ages when screening was less extensive. In all time periods, a strong association was found between older age at diagnosis and poorer prognosis. Conclusion. Although alternative explanations for our findings must be seriously considered, the most obvious interpretation is that cytologic screening reduces mortality from cervical cancer by earlier diagnosis of invasive disease.

Detection Of High-Risk Human Papillomavirus In The Cervix And Semen Of Sex Partners

Abstract: To investigate the possibility of sexual transmission of human papillomavirus (HPV), 53 married couples were examined for the presence of HPV-16 and -18 DNAs in the uterine cervix and semen using the polymerase chain reaction method. Twenty-three of the 53 women and 12 of the 53 male partners were positive for HPV-16 DNA. No HPV-18 DNA was detected in samples from any of the partners. In 27 pairs, both partners were negative for HPV DNA in cervix or semen; in the remaining 26 pairs, at least 1 of the partners was HPV-16-positive. In 9 (35%) of these 26 pairs, both partners were infected. Furthermore, 9 (75%) of the 12 women with HPV-positive partners were HPV-positive, while 9 (39%) of the 23 men with HPV-positive female partners were HPV-positive. These findings suggest an increased risk of HPV transmission via sexual intercourse, thereby underscoring the importance of preventive care against HPV infection during intercourse.

p53 mutations in cervical carcinogenesis--low frequency and lack of correlation with human papillomavirus status.

Abstract: p53 gene aberrations are common in human malignancies, and recent studies suggest that in cervical carcinoma p53 function is inactivated either by complex formation with human papillomavirus (HPV) E6 product or by gene mutation. Using polymerase chain reaction (PCR) followed by denaturing gradient gel electrophoresis (DGGE), we examined the mutational status of the four 'hotspot' regions of the p53 gene in 47 primary cervical carcinomas. HPV status was determined, also by PCR. In 20 of these cases, we examined for loss of heterozygosity (LOH) on chromosome 17p13. In the 47 carcinomas, and in a further 68 biopsy specimens from normal, premalignant and malignant cervix, we investigated aberrant immunocytochemical expression of p53. Immunocytochemically, abnormal p53 expression was detected in 13 of 115 cases (8/57 carcinomas). Somatic mutation in p53 was detected in 1 of 47 cervical carcinomas; 36 were positive for HPV 16, 18 or 33. A low level of allele loss (3 out of 20 cases) was detected on chromosome 17p, occurring in both HPV-positive and HPV-negative cases, and in cases with and without p53 mutations. We conclude that somatic mutation in the hotspot regions of the p53 gene occurs infrequently in cervical carcinomas; that immunocytochemically detectable levels of p53 are also infrequent; and that there is no consistent correlation between p53 mutational status, LOH on chromosome 17p or HPV status in these cancers.

Human papillomavirus detection by hybrid capture and its possible clinical use

Abstract: AIMS--To determine the sensitivity of the hybrid capture method for human papillomavirus (HPV) detection and potential clinical uses as a screening method for the identification of cervical intraepithelial neoplasia. METHODS--The presence of oncogenic types of HPV was tested for in samples taken from the cervix at colposcopy, and compared with detection by polymerase chain reaction (PCR) in 60 patients. Both sets of results were corrected with the pathology determined by biopsy and smear cytology. RESULTS--Hybrid capture detection showed 86% agreement with PCR. Eighty three percent of CIN 3 lesions, 62% of CIN 2, 59% of CIN 1 and 21% of normal controls were positive for oncogenic HPV types. CONCLUSION--The hybrid capture detection method is reliable, sensitive, and easy to use. The addition of HPV testing to cytological screening would detect a greater proportion of cervical dysplasia with a higher false positive rate.

Method for the diagnosis of cervical changes

Abstract: The present invention relates to a method and instrumentation for detecting the changes in cervical connective tissues associated with cervical dilation or effacement. This method uses an optical system to determine changes by laser or other light induced native fluorescence spectroscopies (LIF) of cervix. The method is non-invasive and instant. It operates by shining excitation light of a selected wavelength on cervical tissue and measuring fluorescent emissions. The measurement is completed in seconds. This method is an excellent fit with the clinical needs for determining the status of cervical dilation.

An electronic approach to the detection of pre-cancer and cancer of the uterine cervix: a preliminary evaluation of Polarprobe.

Abstract: We report on the testing of a prototype of an electronic device for the detection of cervix cancer and its precursors, known as the Polarprobe. The device monitors three aspects of the cervix tissue; two relate to optical properties and the other to dielectric characteristics. The response to tissue stimulation takes the form of an energy pattern which, in conjunction with spectroscopic discriminants, can be digitized to prepare an algorithm. The pattern algorithms are sufficiently characteristic to be afforded names which correspond to tissue states recognizable as normal or abnormal by the clinician. On a tissue observation basis the previously established recognition algorithms derived from 106 volunteers produced assessments which related strongly to colposcopy/histology diagnoses obtained on 77 additional volunteers. This concordance between colposcopy/histology and Polarprobe diagnoses on this primary analysis subgroup ranged from 85% on low-grade intraepithelial abnormalities, and 90% on high-grade cervical intraepithelial squamous neoplasia, to 99% on invasive cancer. An extrapolation of these results suggests false-positive/false-negative rates in the order of 10% are achievable with the current Polarprobe device.