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ABSTRACT: Oral tongue squamous cell carcinoma (OTSCC) is an aggressive cancer associated with poor prognosis. Methods for determining the aggressiveness of OTSCC from analysis of the primary tumour specimen are thus highly desirable. We investigated whether genomic instability and proliferative activity (by means of Ki-67 activity) could be of clinical use for prediction of locoregional recurrence in 76 pretreatment OTSCC paraffin samples (stage I, n=22; stage II, n=33; stage III, n=8; stage IV, n=13). Eleven surgical tumour specimens were also analysed for remnants of proliferative activity after preoperative radiotherapy. Ninety-seven percent of cases (n=72) were characterised as being aneuploid as measured by means of image cytometry. Preoperative radiotherapy (50-68 Gy) resulted in significant reduction of proliferative activity in all patients for which post-treatment biopsies were available (P-value=0.001). Proliferative activity was not associated with response to radiation in stage II patients. However, we report a significant correlation between high proliferation rates and locoregional recurrences in stage I OTSCC patients (P-value=0.028). High-proliferative activity is thus related to an elevated risk of recurrence after surgery alone. We therefore conclude that Ki-67 expression level is a potentially useful clinical marker for predicting recurrence in surgically treated stage I OTSCC.
British Journal of Cancer 10/2008; 99(7):1121-8. · 5.04 Impact Factor
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ABSTRACT: The primary aim of this study was to investigate if the expression of the DNA damage identifying protein DNA-PKcs known to be involved in DNA repair after treatment with ionising radiation can be used as a predictive marker for radiotherapy (RT) response in cervical cancer. Formalin-fixed primary tumour biopsies from 109 patients with cervical cancer, FIGO-stage IB-IIA, treated with preoperative brachytherapy followed by radical surgery were analysed by immunohistochemistry. In addition, correlation studies between early pathological tumour response to radiation and expression of Ku86, Ku70, Mdm-2, p53 and p21 in primary tumours were also performed. We found that tumour-transformed tissue shows positive immunostaining of DNA-PKcs, Ku86 and Ku70, while non-neoplastic squamous epithelium and tumour-free cervix glands show negative immunoreactivity. Expression of DNA-PKcs positively correlated with both Ku86 and Ku70, and a statistically significant correlation between the Ku subunits was also found. After RT, 85 patients demonstrated pathologic complete remission (pCR), whereas 24 patients had residual tumour in the surgical specimen (non-pCR). The main finding of our study is that there was no correlation between the outcome of RT and the expression of DNA-PK subunits. Positive p53 tumours were significantly more common among non-pCR cases than in patients with pCR (P=0.031). Expression of p21 and Mdm-2 did not correlate with the outcome of RT.
British Journal of Cancer 07/2006; 94(11):1683-9. · 5.04 Impact Factor
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ABSTRACT: Delayed chemotherapy-induced nausea is still a clinical problem, and the underlying mechanisms are poorly understood. Previous studies have suggested that corticosteroids are involved, although the mechanisms by which corticosteroids exert their antiemetic effect are largely unknown. We have previously found impaired control of delayed nausea after injection of dexamethasone. The possibility of differences in the recovery of the hypothalamic-pituitary-adrenal (HPA) axis after injection of dexamethasone was investigated in patients (n = 5) with gynaecological cancer being treated with platinum-based chemotherapy and in healthy female volunteers (n = 10). Urinary free cortisol was used to assess the levels of endogenous cortisol. Results showed that in both patients and controls injections of dexamethasone led to a significant decline in endogenous cortisol levels in 24 h and a subsequent significant recovery in the next 24 h. We conclude that the recovery of the HPA axis is rapid after a single dose of dexamethasone in patients and controls. The absence of an abnormal response pattern in patients makes it probable that the suppression and recovery of the HPA axis after injection of dexamethasone does not influence the corticosteroid-induced rebound effect on delayed platinum-induced nausea.
Supportive Care Cancer 10/2000; 8(5):431-4. · 2.60 Impact Factor
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ABSTRACT: Human papillomavirus (HPV) exists as more than 100 genotypes. It is not well-established whether the different HPV types interfere with infection or pathogenesis by each other. Possible interactions in cervical carcinogenesis between infection with the most common HPV types (6, 11, 16, 18 and 33) were studied in a seroepidemiological case- control study of 218 women with primary untreated cervical cancer and 219 healthy age-matched control women. As previously shown, HPV-16 seropositivity was associated with cervical cancer risk [odds ratio (OR), 2.39], but HPV-16 was not associated with cervical cancer risk among HPV-6 seropositive women (OR, 1.0). The relative excess risk due to interaction between HPV-6 and -16 was -2. 35 (95% confidence interval, -0.04 to -4.65), indicating significant antagonism. The results suggest that infection with HPV-6 may interfere with HPV-16-associated cervical carcinogenesis.
Journal of General Virology 12/1999; 80 ( Pt 11):2931-6. · 3.36 Impact Factor
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ABSTRACT: In women with cervical cancer, treatment causes changes in vaginal anatomy and function. The effect of these changes on sexual function and the extent, if any, to which they distress women are not known.
In 1996 and 1997, we attempted to contact 332 women with a history of early-stage cervical cancer (age range, 26 to 80 years) who had been treated in 1991 and 1992 at the seven departments of gynecological oncology in Sweden and 489 women without a history of cancer (controls) to ask them to answer an anonymous questionnaire about vaginal changes and sexual function.
We received completed questionnaires from 256 of the women with a history of cervical cancer and 350 of the controls. A total of 167 of 247 women with a history of cancer (68 percent) and 236 of 330 controls (72 percent) reported that they had regular vaginal intercourse. Twenty-six percent of the women who had cancer and 11 percent of the controls reported insufficient vaginal lubrication for sexual intercourse, 26 percent of the women who had cancer and 3 percent of the controls reported a short vagina, and 23 percent of the women who had cancer and 4 percent of the controls reported an insufficiently elastic vagina. Twenty-six percent of the women who had cancer reported moderate or much distress due to vaginal changes, as compared with 8 percent of the women in the control group. Dyspareunia was also more common among the women who had cervical cancer. The frequency of orgasms and orgasmic pleasure was similar in the two groups. Among the women who had cervical cancer, the type of treatment received had little if any effect on the prevalence of specific vaginal changes.
Women who have been treated for cervical cancer have persistent vaginal changes that compromise sexual activity and result in considerable distress.
New England Journal of Medicine 06/1999; 340(18):1383-9. · 53.30 Impact Factor
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ABSTRACT: The use of verbal category scales in assessing patient symptoms is evolving, but the extent to which reliability and precision are lost in using them as opposed to a visual analogue scale (VAS) remains uncertain. The present study analyzed the concordance between a four-point verbal category scale and a VAS in assessing nausea intensity in patients undergoing chemotherapy. The analysis of a total of 348 simultaneous ratings by 104 women over four cycles revealed good concordance between the scales. The means of the VAS ratings (range 0-100 mm) corresponding to the four verbal categories divided the scale in four almost equally large parts (no nausea = 0.7, mild = 24.8, moderate = 48.3, severe = 75.1). However, the VAS ranges were wide. On an individual level a one-step change in the verbal category was associated with an average change of 20 mm on the VAS. The choice of scale to use should be based on the need in the particular situation. When measuring intensity of nausea in patients, the VAS is a reasonable choice due to its possibly greater ability to detect changes over time. On the group level, findings on a four-point category scale and a VAS on the average seem similar.
Cancer Nursing 09/1997; 20(4):260-6. · 1.79 Impact Factor
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ABSTRACT: We investigated how residual tumour burden after cytoreductive surgery was related to the occurrence of acute and delayed nausea and vomiting in 101 ovarian cancer patients receiving their first chemotherapy course. The anti-emetic treatment included ondansetron combined with dexamethasone or placebo. After chemotherapy all patients received ondansetron only for 5 days. Two categories of tumour burden (TB) were formed according to the diameter of the greatest residual tumour (< 2 cm = minimal TB and > or = 2 cm = large TB). Self-reports of nausea and vomiting were obtained for 15 days. Other potential predictor variables were assessed and included in multivariate analyses. Patients with large compared with minimal TB had more delayed emesis, especially on days 2-7. They also had more acute nausea. The aggravating effect associated with large residual TB was more evident in patients > or = 55 years. During the second week after the chemotherapy the occurrence of nausea was higher in patients > or = 55 years than in those < 55 years. This was seen primarily in patients with large residual TB. Predictors for no delayed emesis at all were anti-emetic treatment with dexamethasone, minimal tumour burden, low neuroticism and no history of motion sickness. The increased risk of "persistent' delayed nausea and vomiting seen in older patients with large tumour burden may have important clinical implications and warrants further attention.
British Journal of Cancer 11/1996; 74(7):1114-9. · 5.04 Impact Factor
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ABSTRACT: In order to provide a large-scale evaluation of the association with cervical cancer of antibodies against human papillomavirus (HPV) antigens, sera from 233 patients with primary, untreated cervical cancer and from 157 healthy age- and sex-matched blood donors were analyzed for IgG and IgA antibodies against HPV-derived peptide antigens and against bovine papillomavirus. Several serological responses were strongly associated with cervical cancer, notably the IgG response against the HPV 16 epitopes L1:13 (Relative risk [RR]: 5.3), E2:9 (RR: 2.9), and E7:5 (RR: 4.3), and the IgA response against an HPV 18 E2-derived antigen (245:18, RR: 3.1). HPV DNA in corresponding cervical tumors was analyzed by Southern blotting (SB) and polymerase chain reaction (PCR) in 47 patients. Sixty-six percent of the patients carried HPV DNA as determined by SB, 91% of patients analyzed by PCR. Neither the antibody responses, nor the presence of HPV DNA were significantly associated with the biological properties of the tumors.
Cancer Detection and Prevention 02/1995; 19(5):381-93. · 2.52 Impact Factor
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ABSTRACT: Serum levels of squamous cell carcinoma antigen, carcinoembryonic antigen, CA 125, tissue polypeptide antigen, CRP, alpha 1-antitrypsin and haptoglobin were determined peri- and postoperatively in patients undergoing surgery for benign gynecological disease (n = 18) and postoperatively in women operated for cervical carcinoma (n = 23). The only significant changes seen after premedication, during anesthesia and during surgery were a decrease in serum concentrations of alpha 1-antitrypsin and haptoglobin. We found no postoperative changes in the serum levels of squamous cell carcinoma antigen nor in carcinoembryonic antigen values. However, the latter analyte was influenced by smoking habits. Elevated levels of CA 125 and tissue polypeptide antigen were found in the cancer patients, predominantly within the first 1-3 weeks after surgery. These levels decreased to normal values within 4-6 weeks postoperatively. The median intraindividual coefficients of variation for the tumor markers ranged between 15% and 28% in 30 control women not having surgery. In general, it would seem advisable to wait 6 weeks after surgery before monitoring with CA 125 and TPA is started.
Archives of Gynecology and Obstetrics 02/1992; 251(2):69-78. · 1.28 Impact Factor
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ABSTRACT: In order to evaluate the potentially additive information of some acute phase reactants to that provided by a general tumour marker, pretreatment concentrations of C-reactive protein, alpha 1-antitrypsin, haptoglobin, alpha 1-acid glycoprotein and tissue polypeptide antigen were determined in serum from healthy women, patients with dysplasia/or carcinoma in situ and patients with primary cervical carcinoma. Specificity varied from 95-100% and sensitivity from 16-29%. A correlation with clinical stage was found for all analytes except for alpha 1-antitrypsin. The latter was the most frequently elevated analyte in early Stages (11/43 in Stage Ib/IIa) and uniquely elevated in 7 cancer patients. Although tissue polypeptide antigen predominantly signaled in advanced stages, 3 women in early stages had elevated tissue polypeptide antigen levels. One of these women died and she was also the only woman with raised alpha 1-antitrypsin who died. It is discussed whether elevated tissue polypeptide levels might represent an unfavourable sign for the individual and if alpha 1-antitrypsin is a favourable sign in early stages of cervical carcinoma. C-reactive protein results were obscured in early stages of disease by the presence of intercurrent illness and the results were regarded as inconclusive. Haptoglobin and alpha 1-acid glycoprotein concentrations provided no additional information to serum alpha 1-antitrypsin levels. However, haptoglobin was elevated in 64% (36/56) of the women with dysplasia/carcinoma in situ of the cervix uteri.
European journal of gynaecological oncology 02/1991; 12(5):375-83. · 0.47 Impact Factor
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ABSTRACT: According to previous observations, the variations in serum alkaline DNase activity (SADA) appeared to be useful in monitoring malignant disease. In this study, SADA was measured in 625 individuals to explore nontumor-related factors which may influence SADA levels. The overall range in SADA was 0.2-82.3 kU/l. Women aged 50-79 years had higher (p less than 0.001) levels of SADA than younger females. A similar but less consistent effect of age was noticed in men (0.01 less than p less than 0.05). Older men had lower (0.01 less than p less than 0.05) SADA levels than the older women. Old women substituted with estrogens had lower (0.01 less than p less than 0.05) levels of SADA than those not treated with estrogens. SADA levels in pregnancy as well as postparturition were lower (p less than 0.001) than SADA values in nonpregnant females of similar age. In fertile women, no SADA variation was observed during the menstrual cycle and there was no significant effect of contraceptive pills. In males, SADA seemed unrelated to testosterone or cortisol levels but varied during the day. Smoking, alcohol consumption and drug therapy appeared to be without effect on SADA.
Clinica Chimica Acta 11/1989; 185(1):35-43. · 2.54 Impact Factor
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ABSTRACT: Seven tumour markers, i.e. squamous cell carcinoma antigen (SCC), cancer antigen 125 (CA 125), tissue polypeptide antigen (TPA), neopterin, C-reactive protein (CRP), carcinoembryonic antigen (CEA) and deoxythymidine kinase (TK) were analysed in sera from 104 women with benign and 61 women with malignant gynecologic diseases, in order to create tumour marker panels for various gynecologic malignancies, for monitoring and prediction of disease development. The incidence of elevated tumour marker levels, in cervical carcinoma was 78% when SCC, CA 125 and CEA were used. In ovarian carcinoma one of the markers CA 125, TPA and CEA was elevated in 91% and for endometrial carcinoma the best combination of markers was SCC, CA 125 and CEA (57%). No individual marker was superior to the above combinations. However, in patients with a fatal outcome of their malignant gynecologic disease (mean survival time from serum sampling was 16 months), the incidence of death was highest among those who had TPA elevated (91%) followed by neopterin (86%) and CRP (76%). Although intercurrent diseases affected tumour marker levels the markers picked up a majority of patients with a poor prognosis. This demonstrates the importance of interpreting tumour marker results against a background of detailed clinical information.
European journal of gynaecological oncology 02/1989; 10(6):395-405. · 0.47 Impact Factor
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ABSTRACT: The aim of the study was to acquire knowledge that can be used to refine radical hysterectomy to improve quality-of-life outcome. Data were collected in 1996-1997 by means of an anonymous postal questionnaire in a follow-up study of two cohorts (patients and population controls). We attempted to enroll all 332 patients with stage IB-IIA cervical cancer registered in 1991-1992 at the seven departments of gynecological oncology in Sweden and 489 population controls. Ninety three (37%) of the 256 women with a history of cervical cancer who answered the questionnaire (77%) were treated with surgery alone. Three-hundred fifty population controls answered the questionnaire (72%). Women treated with radical hysterectomy, as compared with controls, had an 8-fold increase in symptoms indicating lymphedema (25% reported distress due to lymphedema), a nearly 9-fold increase in difficult emptying of the bladder, and a 22-fold increase in the need to strain to initiate bladder evacuation. Ninety percent of the patients were not willing to trade off survival for freedom from symptoms. Avoiding to induce long-term lymphedema or bladder-emptying difficulties would probably improve quality of life after radical hysterectomy (to cure cervical cancer). Few women want to compromise survival to avoid long-term symptoms.
International Journal of Gynecological Cancer 16(3):1130-9. · 1.65 Impact Factor
