Human papillomavirus DNA and antibodies to human papillomaviruses 16 E2, L2, and E7 peptides as predictors of survival in patients with squamous cell cervical cancer (original) (raw)
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International Journal of Cancer, 1994
Human papillomavirus (HPV) is a main factor in cervical carcinogenesis. However, data on the correlation of HPV with clinical features and the prognosis of cervical carcinoma remain controversial. The HPV status (positivity, type, copy number) in unfixed tissue specimens of 205 primary invasive cervical carcinomas was determined by Southern blot hybridization. A correlation with comprehensive clinical and histopathologic data and long-time survival was evaluated. HPV DNA was detected in 73% of the cases; 83% of the HPV-positive tumors contained HPV 16. HPV 16 was predominant among squamous-cell carcinomas (SCC) (p = 0.05). HPV 16 copy number was higher in keratinizing tumors (p < 0.05), and elevated levels of the SCC antigen were more common in patients positive for HPV 16 (p < 0.03). No association was found between the HPV status and 8 other clinical and histopathologic variables. Multivariate analysis after a median follow-up of 73 months demonstrated longer survival for patients with lower clinical stage (p = 0.001) and keratinizing SCC (p = 0.005). Women with HPV-negative tumors had a higher risk of death (RR 1.51; p = 0.07). HPV
Human papilloma virus has no prognostic significance in cervical carcinoma
European Journal of Cancer, 1996
The prognostic significance of the detection of HPV (human papilloma virus) DNA in cervical carcinoma was evaluated in 223 cases treated &om January 1988 to November 1989. HPV DNA was detected by PCR (polymerase chain reaction) on fkesh tumour specimens obtained before therapy was started. HPV DNA of any type was detected in 93.3% of all tumours, HPV16 was the predominant type and was detected in 69% of cases. HPV18 was more fkequent in adeno-and adenosquamous carcinoma than in squamous cell carcinoma and occurred more often in poorly differentiated tumours than in more highly differentiated tumours. Patients with HPV negative tumours were on average older than patients with tumours containing HPV. Neither presence of HPV DNA nor HPV type had prognostic significance. In 63 women with early stage tumours submitted to surgery, no difference was found in the fkequency of lymph node metastasis, vessel invasion or prognosis related to HPV type. We conclude that neither the presence nor the type of HPV DNA had any prognostic significance in cervical carcinoma. Copyright 0 1996 Elsevier Science Ltd
The Open Virology Journal, 2008
The prognostic significance of human papillomavirus (HPV) DNA and E6/E7 mRNA, the presence of specific types, and the physical state of HPV DNA, were studied in 202 cervical squamous cell carcinomas. Absence or nondetectable levels of high-risk (types 16, 18, 31, 33, 35, 45, 52 and 58) E6/E7 mRNA, using the real-time nucleic acid sequence based amplification (NASBA) assay, and absence of HPV high-risk/HPV 6, 26, 66, 69, 73 (all methods collectively) were associated with poor overall survival in univariate analysis (P = 0.04 and P = 0.03, respectively) and had independent prognostic value in multivariate analysis (P = 0.01 and P = 0.03, respectively) including FIGO stage and age. Based on the individual results of type-specific PCR and in situ hybridization (ISH), the presence of HPV DNA was not found to be a prognostic factor. Likewise, concerning the presence of specific HPV types and the HPV integration status (determined by ISH), no prognostic significance was found. Mutation analyses of the TP53 gene revealed mutations in 3 of the 6 HPV negative samples (50%).
Human papillomavirus DNA and virus-encoded antigens in cervical carcinoma
The Medical journal of Malaysia, 1997
The present study was undertaken to evaluate the prevalence of HPV in formalin-fixed, paraffin-embedded cervical carcinoma tissues using PCR followed by non-radioactive Southern hybridization with type-specific oligonucleotides for HPV 16 and 18. In addition, the tissue sections were immunohistochemically screened with two monoclonal antibodies, for expression of HPV 16 L1 and HPV 18 E6 proteins. A total of 57 of 60 cervical carcinomas (95.0%) were found with HPV using both techniques. HPV 16 and HPV 18 were present in equal proportions. Results of both DNA hybridization and immunohistochemistry were in agreement for the majority of the cases. HPV 16 and 18 DNA and virus-encoded antigens, L1 and E6 were found highly prevalent in these cervical carcinomas. Due to the high prevalence of HPV with cervical carcinoma in Malaysia, the implementation of routine diagnosis for the virus in cervical biopsies would be clinically useful.
Human Papillomavirus Type 18: Association With Poor Prognosis in Early Stage Cervical Cancer
Background: Cervical carcinoma is a leading cause of mortality from cancer among women worldwide, accounting for approximately 160 000 deaths annually. Prognosis in patients with this disease is dependent on several well-established clinical features (stage of disease and age of patient) and pathologic features (lymph node status, grade of tumor, and depth of invasion). Although the features associated with poor clinical outcome have been well studied, molecular markers such as human papillomavirus (HPV) type that may reflect the underlying biologic basis for clinical behavior are poorly understood. Purpose: To test the hypothesis that differences in survival among patients with cervical carcinoma are associated with HPV DNA type, we conducted a historical cohort study of patients treated at our institutions over a 10-year period. Methods: Fresh primary tumor tissue samples from 291 women with all stages of cervical carcinoma diagnosed from April 1983 through August 1993 were rapidly frozen and stored at -70 °C until analysis. High-molecular-weight DNA was extracted and purified by homogenization, proteinase K digestion, phenol extraction, ammonium acetate salt displacement, ethanol precipitation, and ribonuclease treatment. HPV nucleotide sequences were amplified from tumor DNA samples by polymerase chain reaction with the use of both consensus LI (MY09/MY11) primers that recognize more than 25 HPV types and modifications of type-specific primers developed for HPV types 16, 18, and 6. Clinical data were abstracted from hospital, office, and tumor registry records. Univariate analysis was conducted using Student's t test and chisquared tests. Survival curves were estimated by use of the Kaplan-Meier method; differences between groups were examined by the logrank test. Multivariate survival analysis was performed according to the Cox proportional hazards model. Results: HPV DNA was detected in 247 (85%) of 291 tumors: HPV16 in 52%, HPV18 in 20%, other HPV types in 13%, and no HPV DNA in 15%. Eighty-eight percent of squamous tumors contained HPV DNA compared with 79% of adenocarcinomas, the latter harboring predominantly HPV18. Women 45 years old or younger with a history of cigarette smoking tended to have HPV DNA in their tumors, but the HPV type was not associated with established prognostic factors such as stage, grade, lymph node metastasis, or depth of stromal invasion. After a median follow-up of 38.9 months, among potential prognostic factors of patient age, histologic cell type, grade, and HPV DNA status, only stage was predictive of survival in the entire study population. However, among the 171 patients treated with type III radical hysterectomy (removal of uterus and upper vagina along with other tissues extending to the pelvic wall) and pelvic lymphadenectomy (removal of all lymphatic tissue in the pelvis), multivariate analysis determined that lymph node status (adjusted risk ratio [RR] = 3.12; 95% confidence interval [CI] = 1.35-7.21), depth of stromal invasion (adjusted RR = 3.14; 95% CI = 1.05-9.34), and the presence of HPV18 DNA (adjusted RR = 2.59; 95% CI = 1.08-6.22) were statistically significant predictors of survival. Conclusion: HPV 18 DNA type is an independent prognostic factor in patients with cervical carcinomas treated with radical hysterectomy and pelvic lymphadenectomy. Implications: The use of molecular markers such as HPV DNA type may allow the identification of patients with early stage cervical cancer at high risk for disease recurrence.
Human Papillomavirus DNA in Plasma of Patients with HPV16 DNA-positive Uterine Cervical Cancer
Japanese Journal of Clinical Oncology, 2010
The squamous cell carcinoma antigen is considered the most accurate serologic tumor marker for uterine cervical carcinoma. However, serum squamous cell carcinoma antigen levels were found to correlate significantly with clinical severity of atopic dermatitis and chronic renal failure. The present study was conducted in patients with human papillomavirus 16 DNA-positive uterine cervical cancer to determine the plasma level of human papillomavirus 16 DNA and the diagnostic values of plasma human papillomavirus DNA in these patients. Forty-three human papillomavirus 16-positive patients with cervical intraepithelial neoplasia or uterine cervical squamous cell carcinoma were recruited in this study. The diagnosis was cervical cancer in 20 patients, high-grade squamous intraepithelial lesions in 21, low-grade squamous intraepithelial lesions in 1 and negative for intraepithelial lesion or malignancy in 3 patients. Before any treatment, blood samples were collected from all patients. For analysis of human papillomavirus DNA in plasma of patients with cervical cancer, quantitative polymerase chain reaction fluorescent assay for human papillomavirus 16 was performed using human papillomavirus 16 primers and SYBR Green dye using the LightCycler 480 SW1.5 apparatus. Plasma human papillomavirus 16 DNA was detected in only 30.0% of the patients with human papillomavirus 16-positive cervical cancer and in none of normal controls. The copy number of plasma human papillomavirus 16 DNA was higher in patients with invasive cancer than in those with cervical intraepithelial neoplasia (CIN3), micro-invasive cancer and in normal individuals. These results indicated that the plasma human papillomavirus DNA level could be potentially used as a marker of low-invasive cervical cancer tumors in patients with normal squamous cell carcinoma antigen levels before treatment.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2002
Human papillomaviruses (HPVs) play a central role in the development of cervical carcinoma. Plasma DNA from 232 patients taken at diagnosis or after treatment for invasive cervical cancer (n = 175) or carcinoma in situ (n = 57) and 60 normal controls were examined for HPV-16 or HPV-18 E7 DNA by conventional and real-time quantitative PCR assays. We found HPV-16 or HPV-18 E7 DNA in 6.9% (11 of 175) of invasive cervical cancer cases (18.1% of cases positive for HPV-16 or HPV-18 at the genital tract), 1.8% (1 of 57) of carcinoma in situ, and 1.7% (1 of 60) of normal controls by conventional PCR. Quantitative PCR identified the highest concentrations of HPV DNA (copy number of HPV/ml of plasma) in patients with invasive cervical cancer (mean, 11,163; median, 183.5), followed by a level of 8 in the single carcinoma in situ case and 0 copies in the normal control initially positive by conventional PCR. HPV DNA can be detected in the plasma of some patients with HPV-positive cervical tumor...