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We have previously demonstrated in primary cancer of the uterine cervix that tumor hypoxia, as determined polarographically, is strongly associated with clinical malignant progression of the disease. Having applied a similar methodological approach to investigate loco-regional relapses, we found a pronounced shift to more hypoxic oxygenation profiles in the recurrent tumors than in the primary tumors. Median pO 2 values in 53 pelvic recurrences were significantly lower than the median pO 2 values of 117 primary tumors of comparable sizes (7.1 ؎ 1.1 mmHg vs. 12.1 ؎ 1.0 mmHg, p ‫؍‬ 0.0013). The differences in tumor oxygenation between primary and recurrent tumors mirrored the differences in the patients' 5-year survival probabilities. In the cohort of patients with pelvic relapses, median tumor pO 2 We have shown in primary cancer of the uterine cervix that tumor hypoxia as determined polarographically, not only indicates decreased radiocurability but is generally associated with an aggressive behavior of the disease (Höckel et al., 1993a, b; 1996a, c). Here, we report the results of tumor oxygenation measurements in loco-regional recurrences of cervical cancer. The results further support the thesis that tumor hypoxia is associated with malignant progression (Brizel et al., 1996; Höckel et al., 1996a). MATERIAL AND METHODS PatientsSince 1989 we have been prospectively measuring tumor oxygenation in patients with primary cancer of the uterine cervix of Ͼ2 cm clinical tumor size, and in patients with pelvic recurrences that are transvaginally accessible for electrode insertion. The study has been approved by a Medical Ethics Committee. All patients gave informed consent before being enrolled in the study. TumorsA thorough clinical work-up was performed in all patients with primary and recurrent cancers to completely characterize each tumor. Tumor sizes and locations were assessed in all cases by experienced gynecologic oncologists by inspection, palpation and endoscopy (under anesthesia, if necessary) and pelvic computed tomography (CT) and/or magnetic resonance imaging (MRI) scans. The histological type of all primary and recurrent tumors was verified by core biopsies. Tumor oxygenation measurementsTumor oxygenation was measured pre-therapeutically with an Eppendorf polarographic system. pO 2 readings were performed in conscious patients in the lithotomy position along linear tracks, first in the subcutaneous fat of the mons pubis followed by tumor measurement. Details of the pO 2 measurement in primary cervical cancer have been reported (Höckel et al., 1991;1993a, b;1996a). Pelvic recurrences had to be (1) visible or palpable transvaginally and (2) of more than 2 cm in size for tumor oxygenation measurements. Two measuring tracks at different intravaginal entry points in the direction of the major tumor mass were taken.Along one track, 25-35 point measurements 0.7 mm apart starting at a tissue depth of 5 mm were recorded. Atmospheric pressure and intravaginal temperature were monitored at the time of the pO 2 ...

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The objective of this study was to assess whether the presence of human papillomavirus (HPV) DNA and/or several genotypes of HPV DNA in cervical cancer are correlated with several clinicopathologic parameters of well-defined prognostic significance and whether virologic parameters are predictors of long-term survival in cancer patients. Two hundred twenty three cases of cervical cancer patients included in this retrospective study underwent follow-up evaluation. Survival and cause of death were examined for 204 (91.4%) patients, with a mean follow-up time of 4.4 years. HPV DNA was detected using the highly sensitive polymerase chain reaction (PCR) method followed by HPV DNA sequencing for HPV genotyping. These results were correlated with well-defined clinicopathologic parameters and survival data. HPV DNA was detected by PCR in 150 of 193 (73.4%) tissue specimens of cervical cancer patients. DNA sequence analysis revealed the presence of HPV 16 (n = 68, 45.3%), HPV 18 (n = 49, 32.6%) and rare HPV types (n = 33, 22.1%). HPV genotypes correlated significantly with histologic tumor types, node status, tumor oxygenation, blood vessel invasion, and lymph space involvement. The presence of HPV DNA in cervical cancer as well as the genotype of HPV 16 could also be confirmed as significant prognostic factors in the univariate Cox regression analysis (RR 2.856, P < 0.003 resp. RR 3.444, P < 0.0001). In the multivariate analysis, however, HPV DNA status failed to be of prognostic relevance. Exclusively HPV 16 appears to have an independent impact on the overall survival in cervical patients (RR 3.653, P < 0.002). We conclude that the detection of HPV 16 genotype may play an important adjunct role in assessing prognosis of cervical cancer patients. The clinical impact of the presence of HPV DNA in primary tumors of uterine cervix remains to be investigated in further studies, and the exact mechanisms by which HPV influences the prognosis of cervical cancer patients have to be defined.

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