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PubMed2003

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) negatively affect overall survival in carcinoma of the cervix treated with radiotherapy.

PURPOSE: The purpose of this study was to examine a variety of biomarkers in carcinoma of the cervix to better characterize (1). the natural history of the disease, (2). response to radiotherapy (RT), and (3). potential for new therapeutic strategies. MATERIALS AND METHODS: Fifty-five patients with Stage IB-IVA carcinoma of the cervix, treated with definitive intent RT, and on whom tumor tissue blocks were available were included in this study. Charts were reviewed for clinical parameters and disease status. Immunohistochemistry was performed for epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), CD34, topoisomerase II alpha (topo-II), and cyclooxygenase-2 (COX-2). Univariate and multivariate Cox proportional hazards modeling was performed with disease-free survival (DFS) and overall survival (OS) as the end points. Biomarkers were evaluated for correlation between various prognostic factors. RESULTS: In this series of 55 patients with carcinoma of the cervix treated with definitive RT, only stage was significant on univariate analysis for DFS (p < 0.0001). On univariate analysis, increasing FIGO stage (p < 0.0001) and membranous staining of EGFR (p < 0.037) indicated diminished OS. On multivariate analysis for DFS, COX-2, VEGF, and stage were significant (p = 0.012, p = 0.014, and p = 0.03, respectively), with increased expression indicating a worse prognosis. For OS, multivariate analysis revealed that VEGF, EGFR, and FIGO stage were significant (p = 0.005, p = 0.011, and p < 0.0001, respectively). Significant direct correlations were identified between VEGF and CD34 (p = 0.04), COX-2 and topo-II (p = 0.04), COX-2 and grade (p = 0.04), and tumor size and clinical stage (p = 0.04). CONCLUSION: Multivariate analysis revealed that increased staining for VEGF and COX-2 indicated diminished DFS, and VEGF and EGFR identified patients at increased risk of death. A significant direct correlation between VEGF and CD34 implicates the process of angiogenesis. Topo-II is a proliferative marker and it correlated directly with COX-2, indicating that expression of COX-2 may be greater in more proliferative tumors. Increased expression of EGFR, VEGF, and COX-2 has identified patients with a worse prognosis in cancer of the cervix. These data support the investigation of therapeutics that target these proteins in carcinoma of the cervix.

Adenocarcinoma↗
PubMed1997

Heterogeneity of polarographic oxygen tension measurements in cervix cancer: an evaluation of within and between tumor variability, probe position, and track depth.

PURPOSE: To evaluate the heterogeneity of cervix cancer oxygenation as measured using the Eppendorf polarographic electrode and define the optimal number of measurements required to adequately sample a cervix cancer. METHODS AND MATERIALS: Two to 6 tracks with 20-30 measurements per track were obtained in each of the 44 patients evaluated. One hundred sixty-eight tracks and 4719 measurements formed the basis of this analysis. Median pO2 and hypoxic proportion (HP5), defined as the percentage of pO2 values <5 mmHg, were calculated for each track and for each tumor. Within-tumor (W) and between-tumor (B) variability in oxygenation was evaluated using a variance component analysis. The standard error of the measured HP5 with each additional track in each patient was analysed as a function of the total number of tracks. RESULTS: The ratio W/W + B was 0.67 and 0.76 for median pO2 and HP5, respectively, indicating that multiple measurements are needed to adequately sample a tumor. The median value of the standard error of the HP5 decreased from 7.0 to 4.0% from the first to the fifth track, respectively. It was estimated that adding the sixth track would only result in a small change (<0.3%) in the standard error. There was no significant difference in oxygen tension measurements as a function of the location of the measurements around the circumference of the cervix or the depth along the measurement tracks. CONCLUSIONS: There is significant within tumor variability in oxygen tension in cervix cancer. Five tracks with 20-30 measurements per track is optimal to sample the oxygenation status of a cervix cancer. The present data does not suggest that there is a significant difference related to the position in the tumor at which the pO2 measurements were taken.

Adult↗
PubMed2003

Induction of labour with a favourable cervix and/or pre-labour rupture of membranes.

Premature rupture of membranes (PROM) occurs in 8% of term deliveries. In this situation labour induction with prostaglandins, compared with expectant management, results in a reduced risk of chorioamnionitis, neonatal antibiotic therapy, neonatal intensive care (NICU) admission, and increased maternal satisfaction. The use of prostaglandin is associated with an increased rate of diarrhoea and use of analgesia/anaesthesia. Compared with oxytocin, prostaglandin induction results in a lower rate of epidural use and internal fetal heart rate monitoring but a greater risk of chorioamnionitis, nausea, vomiting, more vaginal examinations, neonatal antibiotic therapy, NICU admission and neonatal infection. Women should be informed of the risks and benefits of each method of induction.Misoprostol is gaining increasing interest as an alternative induction agent. It appears to be an effective method of labour induction with term PROM. Further research is needed to identify the preferred dosage, route and interval of administration, and to assess uncommon maternal and neonatal outcomes. There has been limited research on the use of prostaglandins, including misoprostol, for induction of labour with a favourable cervix and intact membranes. Compared with intravenous oxytocin (with and without amniotomy), labour induction using vaginal prostaglandins in women with a favourable cervix (with and without PROM) results in a higher rate of vaginal delivery within 24 hours and increased maternal satisfaction. In women with a favourable cervix, artificial rupture of membranes followed by oral misoprostol has similar time to vaginal delivery compared with artificial rupture of membranes followed by oxytocin. Further research with prostaglandins, including misoprostol, is needed to evaluate other maternal and neonatal outcomes in women being induced with a favourable cervix. No form of prostaglandin induction in women with PROM or favourable cervix has proven clearly superior to oxytocin infusion.

Administration, Intravaginal↗
PubMed2000

Angiogenesis in the uterine cervix.

Our objective was to present current data pertaining to angiogenesis of the uterine cervix. We conducted a computerized search to identify relevant studies published in the English language literature. MEDLINE, Current Contents and Index Medicus were searched utilizing the terms: angiogenesis, uterine cervix, intraepithelial neoplasia, squamous cell carcinoma, and adenocarcinoma, from 1966 through June 1999. In contrast to the cyclic phases of the menstrual cycle of the ovary and endometrium in which angiogenesis plays a significant physiologic role, angiogenesis in the uterine cervix is involved primarily in neoplastic processes. These include intraepithelial disease, human papilloma-related disease, and microinvasive and invasive squamous cell and adenocarcinoma of the cervix. In invasive squamous cell and adenocarcinoma of the uterine cervix, angiogenesis appears to be a prognostic indicator for overall survival and disease-free survival. Initial trial studies with anti-angiogenic (angio-inhibitor) therapy such as TNP-470 have been reported and concurrent antitumor activity observed in a limited number of patients with advanced (inoperable or metastatic) disease.

Journal Article↗
PubMed1996

The continuing increase in adenocarcinoma of the uterine cervix: a birth cohort phenomenon.

BACKGROUND: Adenocarcinoma of the uterine cervix has been reported to be increasing among young white women and earlier studies suggest a birth cohort pattern for the observed increase. No study, however, has examined the time trends of adenocarcinoma of the cervix by birth cohort. METHODS: Using Surveillance, Epidemiology, and End Results (SEER) data through 1990, the current study is designed to examine the time trends of invasive adenocarcinoma by birth cohort. An age-period-cohort model was fitted to the annual-age-specific rates to identify the components of birth cohort and time period as determinants of the observed time trends. RESULTS: The results from this study clearly show that invasive adenocarcinoma of the uterine cervix has been increasing in both whites and blacks, but the increase is statistically significant only among whites, reaching 4.2 percent per year for those born since 1935. The results also show that the recent increase in invasive adenocarcinoma started among those born around the mid 1920s, and a strong birth cohort effect is largely responsible for the observed increase. CONCLUSION: Invasive adenocarcinoma of the uterine cervix is increasing among recent birth cohorts. Analytical epidemiological studies are urgently needed to explore the risk factors responsible for the increase. The time trends for adenocarcinoma of the cervix should also be carefully monitored in the coming years.

Adenocarcinoma↗
PubMed2000

Risk factors for pre-cancerous lesions of the cervix.

Studies on risk factors for pre-cancerous lesions of the uterine cervix have shown strong association with sexual practice. Women with multiple sexual partners and intercourse at early age are at high risk. A role of male partners in further enhancing the risk has been identified. All these support the hypothesis relating to a sexually transmissible aetiological agent. An extensive review of the literature on the risk factors for pre-cancerous lesions of cervix has been carried out. The risk factors were grouped into genital, sexual, chemical, dietary and life factors. Human papilloma virus (HPV) is the major infectious aetiological agent associated with the development of pre-cancerous lesions of cervix. Other co-factors such as multiple sexual partners of the male as well as the female and early age of first intercourse are also involved at the critical aetiological step of progression from low-grade to high-grade lesions. The role of other infectious agents in terms of supportive or interactive effects is not clear. No independent effect for herpes simplex virus 2 on risk is observed. Other risk factors include cigarette smoking, oral contraceptive usage, certain nutritional deficiencies and poor personal hygiene. However, it is not clear whether these factors operate independently from HPV. There is no consistency in the independent effect of these factors on the development of low- to high-grade lesions of cervix. There is a similarity in the patterns of risk between pre-cancerous lesions of the cervix and cervical cancer. Monogamy, late commencement of sexual activity, personal hygiene and use of barrier contraceptive methods help towards primary prevention. In the long-term, primary prevention of cervical neoplasia through HPV immunization of population may be a possibility.

Coitus↗
PubMedDate not supplied

Recurrence of carcinoma cervix in the scar of previous cesarean section: a case report.

Although rare, reports of carcinoma cervix recurring in abdominal incision, episiotomy scars, laparoscopic port sites, and drain sites are available. However, recurrence in the scar of a previous cesarean section (CS) is unreported. A 49-year-old female with a diagnosis of keratinizing squamous cell carcinoma (SCC) of cervix, stage IIB, was treated by radical radiotherapy. She had undergone CS, through midline abdominal incision, for three previous deliveries. Twenty months later, she presented with a nodule of size 2.5 x 2 cm(2) on the 26-year-old abdominal CS scar. Infiltration of the skin and extension into the deeper structures of the abdominal wall was present in an area of 5 x 4 cm(2). There was no evidence of disease on the cervix. A fine-needle aspiration cytologic examination from the nodule revealed keratinizing SCC. Ultrasonography and computerized tomography scan revealed a mass lesion along the abdominal CS scar with subcutaneous nodule and peritoneal extension. Multiple metastatic lesions were present in the liver. She was treated with chemotherapy and radiotherapy. The patient has lived for more than 12.5 months. The first report of recurrence of carcinoma cervix in a CS scar is presented. Literature on surgical scar recurrence in carcinoma cervix is reviewed.

Adenocarcinoma↗
PubMedDate not supplied

Telomerase activity in the vaginal margins of radical hysterectomy in patients with carcinoma of the cervix: correlation with histology and human papillomavirus.

This study was undertaken to evaluate the telomerase activity both in the tumor and in the vaginal margins of radical hysterectomy in patients with squamous cell carcinoma (SCC) of the cervix. Thirty-three patients with SCC of the cervix (study group) and 13 patients with uterine myoma (control group) were prospectively studied. Tissue samples were taken from the tumor or cervix, anterior vaginal margin (AVM), and posterior vaginal margin (PVM). The specimens were analyzed by histopathology, by a telomerase PCR-TRAP-ELISA kit, and by polymerase chain reaction using human papillomavirus (HPV) DNA. The telomerase activity was significantly higher in the tumor than in the benign cervix (P < 0.001). There was no difference in telomerase activity in the AVM and PVM in patients with cervical carcinoma compared to the control group. Telomerase activity was associated with the presence of histologic malignancy in the PVM of patients submitted to radical hysterectomy (P= 0.03). This association was not observed with the presence of HPV in AVM or PVM in the study group. Telomerase activity is a marker of histologic malignancy in patients with SCC of the cervix. There was no association between the telomerase activity and the presence of HPV in vaginal margins of patients submitted to radical hysterectomy.

Adult↗
PubMed1999

Carcinoid syndrome caused by an atypical carcinoid of the uterine cervix.

Neuroendocrine tumors of the cervix are rare and are often under- or misdiagnosed. Because these tumors are very aggressive, early diagnosis and subsequent treatment are warranted. We describe a 46-yr-old woman with carcinoid syndrome caused by an atypical carcinoid of the uterine cervix. At age 44, she had dysplasia on Pap smear and underwent total abdominal hysterectomy with the diagnosis of adenocarcinoma. Fourteen months postoperatively, she developed the carcinoid syndrome and was found to have numerous liver metastases. Histological and immunohistochemical investigations of biopsy specimens from the patient's liver lesions and original cervical lesion ("adenocarcinoma") suggested that this woman had a primary atypical carcinoid of the uterine cervix with metastases to the liver. Treatment with octreotide and alkylating agents decreased the episodes of flushing and diarrhea within 8 weeks. If an adenocarcinoma of the uterine cervix is diagnosed, atypical carcinoid should be in the differential diagnosis. Symptoms of the carcinoid syndrome should be pursued and, if present, a urinary 5-hydroxyindolacetic acid level should be obtained. Timely diagnosis of a neuroendocrine tumor of the cervix may improve survival.

Adenocarcinoma↗
PubMed1977

Mass screening in Sweden for cancer of the uterine cervix. Results and epidemiologic effect.

The mass screening program in Sweden for cancer of the uterine cervix, which was started in 1964, is now almost nation-wide. Approximately a quarter of a million women are screened every year. The attendance varies between 55 and 90%. Approximately two per cent of the screened female population is invited to further examination or treatment. The yield through the mass screening program varies between 3.5 and 10 positive cases per 1000 examined women. The incidence of cancer of cervix is decreasing. This is most evident in those counties, which have been carrying out the screening program for about ten years. The stage distribution in cancer of the cervix has not been changed by the screening program. Mortality in cancer of the cervix is unchanged. There has been an enormous increase in the number of diagnosis of cancer in situ of the cervix, which is a difficult practical problem.

Adolescent↗
PubMed1988

Diagnostic accuracy of outpatient endocervical curettage using conventional and Vabra curettage of the cervix.

With the object of examining the diagnostic accuracy of and pain reaction to endocervical curettage (ECC) either by using a new instrument, Vabra mc cervix, or with a conventional 3 mm metal curette, 298 patients with histologically verified cervical intraepithelial neoplasia (CIN) or cytological suspicion have been involved in a consecutive prospective randomized trial. One hundred and forty-eight patients underwent curettage with the Vabra instrument (vabrasio) followed by conventional curettage; 150 underwent the same procedure, but in reverse order. In 114 patients, CIN was ascertained in one or both trials. Vabra mc cervix found normal histology in 23 of these patients (20%), whereas conventional curettage showed normal histology in 58 patients (51%). Quantitatively, Vabra mc cervix extracted significantly more tissue material than did conventional curettage. The pain intensity when using of Vabra mc cervix was less severe. The present study showed diagnostic accuracy of Vabra mc cervix to be 80% (95% confidence limits: 63.38-80.73), compared with 49% (95% confidence limits: 35.17-54.35) when using conventional curettage.

Ambulatory Surgical Procedures↗
PubMed1990

Second primary cancer after treatment of invasive carcinoma of the uterine cervix, compared with those arising after treatment for in situ carcinomas. An effect of irradiation? A cancer registry study.

A cancer registry cohort of 16,704 cases of invasive carcinoma of the uterine cervix and 56,116 cases of in situ carcinomas of the uterine cervix was followed up and second new primary cancers were recorded. The invasive carcinomas contributed 127,118 woman-years at risk and the in situ carcinomas contributed 453,362 woman-years at risk. The main treatment for the invasive carcinomas had been radiotherapy and for the in situ carcinomas, conization and other types of surgical intervention. 767 new primaries occurred after treatment of invasive carcinoma of the uterine cervix, compared with 644.5 expected. O/E is 1.19. After the in situ carcinomas, 1,421 malignant tumors were observed, vs. 1,188.0 expected (O/E 1.19). If, however, cases of invasive carcinoma of the uterine cervix after in situ carcinomas are excluded, the ratio observed/expected is 1.10. For some sites the increased observed/expected ratios were found after both invasive and in situ carcinomas, which speaks for some common carcinogenic effect other than irradiation (for instance, in bronchus and trachea, pharynx, nose, sinus and larynx, but also in rectum, urinary bladder, other female genital organs, pancreas, lymphosarcoma, as well as acute and non-lymphatic leukemia). A lower risk than expected--after both in situ and invasive carcinoma of the uterine cervix--is observed for breast cancer, cancer of the corpus uteri and for multiple myeloma. However, analyses based on time since treatment provide evidence of a carcinogenic effect of irradiation, especially in intensively irradiated organs such as bladder, rectum, corpus uteri and ovary, and also for acute and non-lymphatic leukemia.

Adult↗
PubMed2002

Endobronchial metastasis of uterine cervix cancer: a two case reports and a review of the literature.

Endobronchial metastasis from uterine cervix cancer defines a bronchoscopically visible nonpulmonary neoplasm metastatic to the bronchus and histologically identical to cervix cancer. Endobronchial metastasis of uterine cervix cancer is rare, therefore, it is difficult to diagnose without pulmonary symptoms or abnormal radiological findings. Moreover, endobronchial metastasis of a nonpulmonary neoplasm is difficult to differentiate from a primary pulmonary neoplasm. The incidence of endobronchial metastasis is increasing because of the regular use of fiberoptic bronchoscopy and the longer survival of cancer patients. This study describes our experience of two patients with pulmonary symptoms and abnormal radiologic findings during the follow up of uterine cervix cancer, who were diagnosed as having endobronchial metastasis from uterine cervix cancer, and includes a brief review of related articles.

Adult↗
PubMed2002

Lymphoepithelioma-like carcinoma of the uterine cervix.

CONTEXT: It has been proposed that Epstein-Barr virus (EBV) plays a role in the etiology of lymphoepithelioma-like carcinoma (LELC) in diverse anatomic locations. In contrast to Asian women, Western women have a low prevalence of LELC of the uterine cervix, and EBV genomes have not been identified. OBJECTIVE: To assess the presence of EBV in LELC of the uterine cervix in 4 white Western women. DESIGN: We collected 4 cases of LELC of the uterine cervix between 1990 and 2000. We performed histologic and immunohistochemical analyses of formalin-fixed, paraffin-embedded tumor samples. We amplified tumor DNA with polymerase chain reaction to detect EBV, human papillomavirus, and simian virus 40 DNAs. RESULTS: Immunohistochemically, tumor cells were positive for cytokeratins and showed strong expression of p53 and MIB-1. Staining for the oncoprotein c-Erb-B2 was focally positive, and staining for Bcl-2 and progesterone receptors was negative. Only one case showed focal nuclear staining for estrogen receptors. All cases had a dense infiltrate of mature lymphocytes expressing T-cell antigens CD45RO, CD3, and CD8. Polymerase chain reaction analysis did not detect EBV, human papillomavirus, or simian virus 40 DNA sequences in any of the 4 cases. One case had positive serologic results for anti-EBV antibodies, indicating a mild or chronic infection. CONCLUSIONS: LELC of the uterine cervix shows the immunohistochemical profile of an aggressive tumor in spite of its good prognosis, in which CD8 cytotoxic suppressor lymphocytes could play an important role. Based on our results, the role of EBV, human papillomavirus, or simian virus 40 in the pathogenesis of LELC of the uterine cervix in Western women remains unclear.

Aged↗
PubMed1999

Lymphocyte-infiltrated FIGO Stage IIB squamous cell carcinoma of the cervix is a prominent factor for disease-free survival.

BACKGROUND: The data of histopathological factors affecting prognosis of patients with FIGO Stage IIB squamous cell carcinomas of the cervix are rarely known. The purpose of this study was to evaluate the histopathological factors rendering therapeutic failure in patients with FIGO Stage IIB. METHODS: Survival and prognostic factors were analyzed in 83 patients with FIGO stage IIB squamous cell carcinoma of the cervix treated with radical hysterectomy and retroperitoneal lymphadenectomy between 1980 and 1989. The relapse-free and overall survival rate was 61.4%. RESULTS: Univariate analysis demonstrated that the degree of lymphoreticular cells infiltrating the cervix, lymph node metastases, barrel shape of the cervix, lymph-vascular space invasion, more than three lymph nodes involved, and bulky tumor size (i.e. tumor size larger than 4 cm) were of prognostic significance in disease-free survival. However, pronounced lymphoreticular cells infiltrating the cervical cancer was the only independent factor to disease-free survival in patients with FIGO stage IIB squamous cell carcinoma treated with radical hysterectomy and retroperitoneal lymph node dissection using multivariate analysis. CONCLUSIONS: We concluded that the immune function of the host might play a crucial role in the process of anti-neoplasm even if local advanced carcinoma of the cervix is noted. Individual therapies may very well have limited efficacy based on the patient's tumor or the inherent host response. How to strengthen the power of the host's immune system may offer another thinking process to treat such a subgroup of patients. More studies are required.

Carcinoma, Squamous Cell↗
PubMed1998

Risk factors for cancer cervix: a case control study.

The present hospital based, group matched case control study was carried out at Gynaecology clinic, Govt. Medical College Hospital, Nagpur, to study risk factors for cancer cervix and investigate their independent and interactive role in the outcome of cervical cancer. The study included 230 cases of cancer cervix and equal number of controls, group matched for age. Univariate analysis included 17 hypothesised risk factors for cancer cervix and identified significance of 10 risk factors. However multiple logistic regression (MLR) analysis recognised and confirmed the significance of illiteracy, poor genital hygiene, long duration of married life, multiparity and early menarche in the ultimate outcome of cancer cervix. Estimates of Attributable Risk Proportions (ARP) and Population Attributable Risk Proportion (PARP) endorsed the etiological and preventable role of these risk factors, respectively. Considering the public health impact of elimination of these risk factors on the cancer cervix problem in this population, development of a preventive strategy based on these risk factors would be an appropriate step towards curtailment of this "Biggest Scourge of womankind".

Case-Control Studies↗
PubMed1999

Malignant lymphoma of the cervix. An unusual presentation and a rare disease.

Malignant lymphomas arising in the uterus are uncommon and are more commonly seen in the cervix than the corpus. Involvement of the cervix as part of a systemic lymphoma is more common than primary lymphoma, but the cervix as the site of presentation is unusual. We report two cases of malignant lymphoma of the cervix. The first patient, a 52-year-old woman, was referred to colposcopy following persistent low grade dyskaryosis on cervical cytology. At colposcopy a Lletz biopsy was performed and a diagnosis of CIN 1 and focal CIN 2 was made. In addition the subepithelial zone revealed a non-Hodgkin's (NHL) B-cell follicular lymphoma. The patient was subsequently staged as NHL Stage 3E. The second patient, a 35-year-old woman, was referred to the gynaecology department with a history of abnormal vaginal bleeding and two abnormal smears. Subsequent cervical biopsy revealed a high grade, large cell, malignant lymphoma, diffuse, B-cell. The patient was staged as Stage IE. Primary lymphoma of the uterine cervix as illustrated in the second case is very unusual. One case had negative cytology and one case had abnormal cells of uncertain origin. This highlights the difficulty of diagnosing cervical lymphoma, a rare but treatable malignancy, on cytology and suggests that cervical biopsy is needed for the confirmation of the diagnosis.

Adult↗
PubMed1999

Abnormal Fhit expression in malignant and premalignant lesions of the cervix.

Genetic analysis of cervical cancer has demonstrated frequent allelic loss in the 3p chromosomal region. The newly described gene FHIT is located at chromosome region 3p14.2, and its expression has been demonstrated previously by reverse transcription-PCR to be abnormal in a majority of cervical cancer cell lines. In this study, 98 different lesions of the cervix were examined for Fhit expression by immunohistochemical staining. Whereas normal cervical epithelium demonstrated diffuse, moderate to intense cytoplasmic staining, many pathological lesions of the cervix displayed reduced or absent Fhit expression. Sixty-one percent of squamous carcinomas and 40% of adenocarcinomas of the cervix had abnormal Fhit expression. Sixty-five preneoplastic lesions of the cervix were examined. Eleven of 33 high-grade squamous intraepithelial lesions and 1 of 12 low-grade squamous intraepithelial lesions had abnormal Fhit expression. In summary, Fhit expression is frequently abnormal in both glandular and squamous cervical cancers, with a higher frequency of Fhit alterations observed in squamous lesions. In addition, abnormal Fhit expression can be detected in some preneoplastic lesions of the ectocervix. Alterations in Fhit expression may be an important marker of early progression in the development of cancers of the cervix.

Acid Anhydride Hydrolases↗