| 1. |
- Andersson, Elin, 1975, et al.
(author)
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Type-dependent E6/E7 mRNA expression of single and multiple high-risk human papillomavirus infections in cervical neoplasia.
- 2012
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In: Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. - : Elsevier BV. - 1873-5967. ; 54:1, s. 61-5
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Journal article (peer-reviewed)abstract
- Coinfection with multiple HPV types is common in cervical lesions, but the biological significance of the individual infections is difficult to establish. Expression of oncogenic E6/E7 HPV mRNA is correlated to risk of malignant progression, commercial assays for genotyping E6/E7 mRNA of all HR-HPV are lacking.
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| 2. |
- Andersson, Elin, 1975, et al.
(author)
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Type-specific HPV E6/E7 mRNA detection by real-time PCR improves identification of cervical neoplasia.
- 2011
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In: Journal of clinical microbiology. - 1098-660X. ; 49:11, s. 3794-3799
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Journal article (peer-reviewed)abstract
- DNA-based HPV assays show high sensitivity but poor specificity in detecting high-grade cervical lesions. Assays detecting mRNA of oncogenic E6/E7 show higher specificity, but lack either detection of all high-risk HPV genotypes or the capacity to specify the detected genotypes. Therefore, a real-time PCR assay detecting type-specific E6/E7 mRNA was developed and the clinical performance evaluated. 210 cervical LBC (liquid based cytology) samples from 204 women were analysed for HPV DNA and mRNA with the in house real-time PCR as well as PreTect HPV-Proofer. The sensitivity of real-time PCR mRNA-detection to detect histologically confirmed CIN2+ (cervical intraepithelial neoplasia grade 2 or higher) were 0.91, compared to 0.95 for DNA-analysis. The specificity was 0.68 compared to 0.38, and the positive predictive value (PPV) was higher for mRNA (0.67 vs 0.52) without any loss in negative predictive value (NPV). The sensitivity of the real-time PCR mRNA-test was somewhat higher than for PreTect HPV-Proofer (0.83 vs 0.75), when analysing for the same genotypes. The specificity was similar (0.76 vs 0.77). When analysing for mRNA of the eight most common genotypes in cervical cancer (HPV16, 18, 31, 33, 35, 45, 52, 58), the sensitivity to detect CIN2+ lesions was 0.87 and the specificity 0.74, with a PPV of 0.70. In conclusion, real-time PCR for detection of HPV E6/E7 mRNA transcripts can be a sensitive and specific tool in screening and investigation of cervical neoplasia. The composition of HPV-types in mRNA-testing needs to be further investigated to optimize sensitivity and specificity.
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| 3. |
- Andrae, Bengt, et al.
(author)
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Screening and cervical cancer cure: population based cohort study.
- 2012
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In: BMJ (Clinical research ed.). - : BMJ. - 1756-1833 .- 0959-8138 .- 1468-5833. ; 344
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Journal article (peer-reviewed)abstract
- To determine whether detection of invasive cervical cancer by screening results in better prognosis or merely increases the lead time until death.
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| 4. |
- Andrae, Bengt, et al.
(author)
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Screening-preventable cervical cancer risks : evidence from a nationwide audit in Sweden.
- 2008
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In: J Natl Cancer Inst. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 100:9, s. 622-9
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Journal article (peer-reviewed)abstract
- Background: The effectiveness of cervical cancer screening programs differs widely in different populations. The reasons for these differences are unclear. Routine and comprehensive audits have been proposed as an ethically required component of screening. We performed a nationwide audit of the effectiveness of the Swedish cervical cancer screening program.Methods: We identified all invasive cervical cancer cases that were diagnosed in Sweden from January 1, 1999, through December 31, 2001, and had been reported to the Swedish Cancer Registry (n = 1230 cases). We verified the diagnoses by histopathologic rereview and matched each case subject to five (population-based) age-matched control subjects who were identified from the National Population Register. The Pap smear screening histories for case and control subjects were reviewed for a 6-year period using the National Cervical Cancer Screening Register, which contains data on essentially all relevant cytological and histological diagnoses in Sweden. Odds ratios (ORs), and their 95% confidence intervals (CIs), of cervical cancer according to screening history were calculated in conditional logistic regression models. All statistical tests were two-sided.Results: Women who had not had a Pap smear within the recommended screening interval had higher risk of cervical cancer than women who had been screened (OR = 2.52, 95% CI = 2.19 to 2.91). This risk was similarly increased for all age groups (Phomogeneity = .96). The risk for nonsquamous cell cervical cancers (OR = 1.59, 95% CI = 1.20 to 2.11) was also increased. Women who had not had a Pap smear within the recommended screening interval had a particularly high risk of advanced cancers (OR = 4.82, 95% CI = 3.61 to 6.44). Among women who had been screened within the recommended interval, those with abnormal Pap smears had a higher risk of cervical cancer than those with normal smears (OR = 7.55, 95% CI = 5.88 to 9.69) and constituted 11.5% of all women with cervical cancer.Conclusions: Nonadherence to screening intervals was the major reason for cervical cancer morbidity. The screening program was equally effective for women of all ages and was also effective against nonsquamous cancers.
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| 5. |
- Elfgren, Kristina, et al.
(author)
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Colposcopic and histopathologic evaluation of women participating in population-based screening for human papillomavirus deoxyribonucleic acid persistence
- 2005
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In: Am J Obstet Gynecol. - : Elsevier BV. ; 193:3, s. 650-657
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Evaluation of colposcopic and histopathological findings in women screened for cervical human papillomavirus deoxyribonucleic acid persistence. STUDY DESIGN: A total of 12 527 women, aged 32 to 38 years old, attending the population-based cervical cancer screening program in Sweden were randomized 1:1 to mock testing or human papillomavirus deoxyribonucleic acid testing by general primer 5+/6+ polymerase chain reaction and subsequent typing. Human papillomavirus deoxyribonucleic acid-positive women with a normal Papanicolaou smear (n=341) and an equal number from the control group were human papillomavirus tested on average 19 months later. One hundred nineteen women with type-specific human papillomavirus persistence and 111 controls were referred to colposcopy, and 84.8% attended. RESULTS: Histopathology from colposcopically directed biopsies confirmed cervical intraepithelial neoplasia grade 2 or 3 in 28 of 100 of the women with human papillomavirus deoxyribonucleic acid persistence and in 2 of 95 among controls. CONCLUSION: Among women with normal Papanicolaou smear attending population-based screening, the positive predictive value of human papillomavirus deoxyribonucleic acid persistence for detection of biopsy-confirmed cervical intraepithelial neoplasia 2 or 3 was 29%.
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| 6. |
- Forslund, Ola, et al.
(author)
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Population-based type-specific prevalence of high-risk human papillomavirus infection in middle-aged Swedish Women.
- 2002
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In: Journal of Medical Virology. - : Wiley. - 1096-9071 .- 0146-6615. ; 66:4, s. 535-541
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Journal article (peer-reviewed)abstract
- Human papillomavirus (HPV) DNA testing can be used to identify women at risk of the development of cervical cancer. The cost-effectiveness of HPV screening is dependent on the type-specific HPV prevalence in the general population. The present study describes the prevalence and spectrum of high-risk HPV types found in a large real-life population-based HPV screening trial undertaken entirely within the cervical screening program offered to middle-aged Swedish women. Cervical brush samples from 6,123 women aged 32-38 years were analyzed using a general HPV primer (GP5(+)/6(+)) polymerase chain reaction-enzyme immunoassay (PCR-EIA) combined with reverse dot-blot hybridization for confirmation and HPV typing by a single assay. In this study, 6.8% (95% CI 6.2-7.5) (417/6,123) were confirmed as high-risk HPV positive. Infections with 13 different high-risk HPV types were detected, of which HPV 16 was the most prevalent type (2.1%; 128/6,123), followed by HPV 31 (1.1%; 67/6,123). Any one of the HPV types 18, 33, 35, 39, 45, 51, 52, 56, 58, 59, or 66 was detected in 3.6% (223/6,123) of the women. Infection with two, three, and five types simultaneously was identified in 32, 5, and 1 women, respectively. The combination of PCR-EIA as a screening test and reverse dot-blot hybridization as a confirmatory test, was found to be readily applicable to a real-life population-based cervical screening. The type-specific HPV prevalence found support in previous modeling studies suggesting that HPV screening may be a favorable cervical screening strategy.
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| 7. |
- Kärrberg, Cecilia, et al.
(author)
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Histological diagnosis and evaluation of the Swede Score colposcopic system in a large cohort of pregnant women with atypical cervical cytology or cervical malignancy signs.
- 2012
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In: Acta obstetricia et gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349.
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Journal article (peer-reviewed)abstract
- Objective. We evaluated the distribution of histological diagnoses in pregnant women with atypical cytology or cervical malignancy signs as well as the usefulness of the Swede Score colposcopic scoring system to reduce the need for diagnostic cervical biopsy. Design. Prospective clinical study. Setting and Population. The study comprised 261 pregnant women undergoing colposcopic investigation because of atypical cervical cytology, dysplastic biopsy changes, recurrent non-obstetric bleeding or pathological appearance of the cervix. Methods. Five colposcopic variables (acetowhiteness, margins plus surface, vessel patterns, lesion size and iodine staining) were scored with 0, 1 or 2 points. Colposcopically directed biopsies or loop electrosurgical excision biopsies were taken from all lesions. Histology was compared with the colposcopic score. Sensitivity and specificity were calculated for each variable, and the combination of all five variables, with high-grade lesions (i.e. cervical intraepithelial neoplasia (CIN2, CIN3 or adenocarcinoma-in-situ (AIS)) as endpoints. Main outcome measures. Colposcopic score (Swede Score) and histology (CIN1, 2, 3; AIS; cancer). Results. The specimens consisted of normal tissue in 19.5% of cases, low-grade lesions (i.e. CIN1, koilocytosis, glandular dysplasia of lower grade than AIS) in 26.1%, high grade lesions in 52.9% and cancer in 1.5%. All high grade lesions and cancers had total Swede Scores of ≥5 and ≥8, respectively. Vessel patterns, lesion size and margins plus surface were most important for high grade lesion detection. Conclusion. The Swede Score seems to be a useful tool in evaluating atypical cervical cytology in pregnant women and may reduce the need for diagnostic biopsies.
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| 8. |
- Lindh, Magnus, 1960, et al.
(author)
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Real-time Taqman PCR targeting 14 human papilloma virus types.
- 2007
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In: Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. - : Elsevier BV. - 1386-6532. ; 40:4, s. 321-4
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Journal article (peer-reviewed)abstract
- BACKGROUND: Subtyping of human papilloma virus (HPV) may enhance the precision of vaginal cytological assessments and will be important for investigating the effect of the recently introduced vaccine against types 16 and 18. OBJECTIVES AND STUDY DESIGN: To evaluate an in-house real-time PCR targeting HPV types 16-18-31-33-35-39-45-51-52-56-58-59-6-11, by analysing 107 liquid-based cytology specimens representing various degrees of dysplasia. RESULTS: In all, 71 samples were HPV positive, with multiple types present in 37 (52%). Comparison with Roche Linear Array on a subset of 24 of these 71 samples showed a good agreement. One or several types were detected in 17/17 (100%) samples with cervical intraepithelial neoplasia grade 2-3 (CIN 2-3), 16/19 (84%) with CIN 1, 32/43 (74%) with Atypical Squamous Cells of Undetermined Significance (ASCUS), and in 6/28 (21%) with benign cytology. Estimates of mean viral load were lower in CIN 1-3 than in ASCUS ( approximately 4000 vs. approximately 25,000 copies/1000 cells), and clearly lower in samples with benign cytology ( approximately 50 copies/1000 cells). CONCLUSION: The HPV rates in groups with different degrees of dysplasia agrees with previous reports and support a strong link between types 16/18 and severe dysplasia. The high rate of multiple type infection might influence the outcome of HPV vaccination. The possible importance of viral load should be further studied.
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| 9. |
- Lundgren-Eriksson, L., et al.
(author)
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Radio-and chemotoxicity in mice during hypothermia
- 2001
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In: Anticancer Res. - 0250-7005. ; 21:5, s. 3269-74
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Journal article (peer-reviewed)abstract
- BACKGROUND: The influence of hypothermia induced by chlorpromazine (10-15 mg/kg given intra-peritoneally) on the survival from radiation and chemotherapy exposure in C57B1-mice, with or without tumour inoculation, was studied. MATERIALS AND METHODS: The mice were exposed to either whole body irradiation (8 Gy), or doxorubicin (15 or 17.5 mg/kg i.p.), or cisplatin (20 mg/kg i. p.) and followed to ensuing death. The control mice maintained a rectal temperature of 38 degres C while those receiving chlorpromazine developed moderate hypothermia of 28 degrees C or 36 degrees C, dependent on the ambient temperature. RESULTS: Hypothermia of 28 degrees C protected the mice from radiation-induced death and acute doxorubicin toxicity, with males gaining more protection than females. The effects appeared dependent on temperature, not on chlorpromazine. Hypothermia protected the mice from acute cisplatin toxicity and increased the anti-tumour effects in both genders. Chlorpromazine itself did not cause toxicity, neither did it change the natural course of tumour progression. CONCLUSION: Hypothermia of 28 degrees C induced by chlorpromazine profoundly reduces radiation, doxorubicin-and cisplatin-induced toxicity in mice with males benefiting more than females. The hypothermia itself, not the chlorpromazine, was responsible for these effects. The anti-neoplastic activity was not compromised; rather, it was enhanced, particularly for cisplatin.
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| 10. |
- Naucler, Pontus, et al.
(author)
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Efficacy of HPV DNA testing with cytology triage and/or repeat HPV DNA testing in primary cervical cancer screening.
- 2009
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 101:2, s. 88-99
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Journal article (peer-reviewed)abstract
- Primary cervical screening with both human papillomavirus (HPV) DNA testing and cytological examination of cervical cells with a Pap test (cytology) has been evaluated in randomized clinical trials. Because the vast majority of women with positive cytology are also HPV DNA positive, screening strategies that use HPV DNA testing as the primary screening test may be more effective.
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