Newsletter

Table of Contents

26.05.2003

Newsletter Nr. 21

Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer.
Epidemiologic classification of human papillomavirus types associated with cervical cancer
Effect of tibolone treatment on intima-media thickness and the resistive indices of the carotid arteries
Semen quality of male smokers and non-smokers in infertile couples.

1. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer

Although tumor-infiltrating T cells have been documented in ovarian carcinoma, a clear association with clinical outcome has not been established. The authors performed immunohistochemical analysis of 186 frozen specimens from advanced-stage ovarian carcinomas to assess the distribution of tumor-infiltrating T cells and conducted outcome analyses. Molecular analyses were performed in some tumors by real-time polymerase chain reaction. CD3+ tumor-infiltrating T cells were detected within tumor-cell islets (intratumoral T cells) in 102 of the 186 tumors (54.8 percent); they were undetectable in 72 tumors (38.7 percent); the remaining 12 tumors (6.5 percent) could not be evaluated. There were significant differences in the distributions of progression-free survival and overall survival according to the presence or absence of intratumoral T cells (P<0.001 for both comparisons). The five-year overall survival rate was 38.0 percent among patients whose tumors contained T cells and 4.5 percent among patients whose tumors contained no T cells in islets. Significant differences in the distributions of progression-free survival and overall survival according to the presence or absence of intratumoral T cells (P<0.001 for both comparisons) were also seen among 74 patients with a complete clinical response after debulking and platinum-based chemotherapy: the five-year overall survival rate was 73.9 percent among patients whose tumors contained T cells and 11.9 percent among patients whose tumors contained no T cells in islets. The presence of intratumoral T cells independently correlated with delayed recurrence or delayed death in multivariate analysis and was associated with increased expression of interferon-gamma, interleukin-2, and lymphocyte-attracting chemokines within the tumor. The absence of intratumoral T cells was associated with increased levels of vascular endothelial growth factor. The presence of intratumoral T cells correlates with improved clinical outcome in advanced ovarian carcinoma.

Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN, Rubin SC, Coukos G. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003 Jan 16;348(3):203-13.

2. Epidemiologic classification of human papillomavirus types associated with cervical cancer.

Infection with human papilloma virus (HPV) is the main cause of cervical cancer, but the risk associated with the various HPV types has not been adequately assessed. Data were pooled from 11 case-control studies from nine countries involving 1918 women with histologically confirmed squamous-cell cervical cancer and 1928 control women. A common protocol and questionnaire were used. Information on risk factors was obtained by personal interviews, and cervical cells were collected for detection of HPV DNA and typing in a central laboratory by polymerase-chain-reaction-based assays (with MY09/MY11 and GP5+/6+ primers). HPV DNA was detected in 1739 of the 1918 patients with cervical cancer (90.7 percent) and in 259 of the 1928 control women (13.4 percent). With the GP5+/6+ primer, HPV DNA was detected in 96.6 percent of the patients and 15.6 percent of the controls. The most common HPV types in patients, in descending order of frequency, were types 16, 18, 45, 31, 33, 52, 58, and 35. Among control women, types 16, 18, 45, 31, 6, 58, 35, and 33 were the most common. For studies using the GP5+/6+ primer, the pooled odds ratio for cervical cancer associated with the presence of any HPV was 158.2 (95 percent confidence interval, 113.4 to 220.6). The odds ratios were over 45 for the most common and least common HPV types. Fifteen HPV types were classified as high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82); 3 were classified as probable high-risk types (26, 53, and 66); and 12 were classified as low-risk types (6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and CP6108). There was good agreement between our epidemiologic classification and the classification based on phylogenetic grouping. In addition to HPV types 16 and 18, types 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82 should be considered carcinogenic, or high-risk, types, and types 26, 53, and 66 should be considered probably carcinogenic.

Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, Snijders PJ, Meijer CJ; International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003 Feb 6;348(6):518-27

3. Effect of tibolone treatment on intima-media thickness and the resistive indices of the carotid arteries.

In a prospective study the effect of tibolone treatment on the intima-media thickness (IMT) of the common carotid artery (CCA) and the resistive indices (RIs) of the CCA and internal (ICA) and external (ECA) carotid and the vertebral arteries (VAs) in twenty postmenopausal women whithout cardiovascular disease were assessed as sonographic markers of atherosclerosis. The ulrasound measurements were made at baseline and after 12 weeks of tibolone treatment.Three months of tibolone treatment decreased the IMT of the CCA (mean +/- SD) from 0.70 +/- 0.22 mm (95% confidence interval [CI], 0.60-0.80) to 0.47 +/- 0.17 mm (95% CI, 0.39-0.55) by 28%. Resistive indices of the CCA, ICA, and VA also decreased significantly.The present study showed that tibolone treatment decreases both the IMT of the CCA and RI of the CCA, ICA, and VA, which appears to be related to its anti-atherosclerotic effect. Nevertheless, the clinical implications of these findings are yet to be investigated.

Erenus M, Ilhan AH, Elter K. Effect of tibolone treatment on intima-media thickness and the resistive indices of the carotid arteries. Fertil Steril. 2003 Feb;79(2):268-73.

4. Semen quality of male smokers and non-smokers in infertile couples.

In a cohort study the effect of cigarette smoking on main sperm variables was investigated in 655 smokers and 1,131 non-smokers. Cigarette smoking was associated with a significant decrease in sperm density (-15.3%), total sperm count (-17.5%), total number of motile sperm (-16.6%), and citrate concentration (-22.4%). The percentage of normal forms was significantly reduced in smokers, and sperm vitality, ejaculate volume, and fructose concentration were slightly but non-significantly affected. Cigarette smoking is associated with reduced semen quality.

Kunzle R, Mueller MD, Hanggi W, Birkhauser MH, Drescher H, Bersinger NA. Semen quality of male smokers and nonsmokers in infertile couples. Fertil Steril. 2003 Feb;79(2):287-91.

Gerhard Leyendecker