| 1. |
- Andersson, Elin, 1975, et al.
(författare)
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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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Ingår i: 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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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Journal of clinical microbiology. - 1098-660X. ; 49:11, s. 3794-3799
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Tidskriftsartikel (refereegranskat)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. |
- Jar-Allah, Tagrid, et al.
(författare)
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Abnormal cervical cytology is associated with preterm delivery: A population based study
- 2019
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 98:6, s. 777-786
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Increasing evidence suggests that cervical intraepithelial neoplasia, with or without subsequent treatment, is associated with preterm delivery. We aimed to explore the association between abnormal cervical cytology of different severity and the subsequent obstetric outcomes such as preterm delivery. Material and methods: The historical register-based cohort study comprised 19822 women in the Western Region of Sweden who had at least one abnormal cervical cytology from 1978 to 2012 before the age of 45 and a subsequent singleton delivery. The reference group comprised 39644 women with normal cervical cytology and a subsequent singleton delivery, matched by age and parity. Data were retrieved from the Swedish National Cervical Screening Registry, linked to the Swedish Medical Birth Register and Statistic Sweden. The study outcomes were spontaneous preterm delivery before 37 and 34weeks, low birthweight (≤2500g), small-for-gestational-age, preterm premature rupture of membranes and neonatal mortality. Multivariable log binominal regression analyses were applied. Results: Preterm delivery before 37weeks was more common among women with abnormal cervical cytology compared with reference group: 6% vs 4.5%; adjusted relative risk 1.30 (95% confidence interval 1.21-1.39). High vs low-grade abnormal cervical cytology implied a higher risk: 7% vs 5.8% (P<0.001). Early preterm delivery before 34weeks, preterm premature rupture of membranes and low birthweight, but not small-for-gestational-age and neonatal mortality, were significantly more common in women with abnormal cervical cytology compared with the reference group. Conclusions: Abnormal cervical cytology may imply an increased risk of preterm delivery. Further studies are needed to investigate whether that risk is related to treatment.
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| 4. |
- Kärrberg, Cecilia
(författare)
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Cervical dysplasia and cervical cancer in pregnancy: diagnosis and outcome
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- ABSTRACT:Cervical cancer is one of the most common types of cancer that is diagnosed during pregnancy. The primary aim in investigation of atypical cervical cytology during pregnancy is to exclude cancer so that further treatment of the lesion can be postponed until after delivery. However, there are difficulties in colposcopic evaluation of cervix due to specific changes and cancer can be overlooked if not multiple biopsies are obtained, but these invasive interventions may increase the risk of bleeding from the vascularized cervix and further obstetrical complications. Thus, there is need for means to reduce the number of biopsies and to find biomarkers that can exclude cervical cancer among pregnant women with atypical cervical cytology. In this thesis, pregnant women were evaluated with the Swede score colposcopic scoring system, due to atypical cervical cytology, dysplasia in biopsy or signs of malignancy in a prospective clinical study. Five colposcopic variables, acetowhiteness, margins plus surface, vessel patterns, lesion size and iodine staining were scored. Colposcopically directed biopsies were taken from all lesions and histology was compared with the Swede score sum. All CIN2+ lesions and cancers had total scores of ≥5and ≥8, respectively. All variables except iodine staining were found significant predictors of CIN2+. In prediction of CIN3+, lesion size, vessel patterns and margins plus surface were significant factors. In a prospective clinical study, surgical/obstetric complications due to colposcopically directed cervical biopsies, loop-biopsies, or LEEP-cones were evaluated. The histology results during pregnancy were compared to that after delivery to evaluate the natural course of dysplastic lesions. Obstetric outcome was recorded and compared to the 54919 other births in the same geographical area during the study period. Only a minor part (12.3%) of the dysplastic lesions showed progression during pregnancy with 54.6% and 33.1% showing persistence and regression, respectively. No surgically-related postoperative bleeding that needed surgical (diathermy/suture) treatment occurred. The miscarriage rate was low (0.8%). There were no differences in mode of delivery, rate of premature birth or other obstetrical variables between the study group and the control cohort. In a retrospective clinical study, medical records were evaluated of all women with cervical cancer diagnosed during pregnancy or within 6 months after parturition between 1993 and 2008 in the Western region of Sweden. Cervical cancer was diagnosed in 47 women (15.6/100 000 deliveries). Sixteen women were diagnosed after abnormal vaginal bleeding and/or discharge. The other women were asymptomatic and diagnosed by abnormal cervical smear or clinical signs at vaginal examination. Nine women had ASCUS as presenting cervical atypia. Cancer was diagnosed in the 1st trimester in 2 women, in the 2nd trimester in 14, in the 3rd trimester in 5 and post-partum in 26 women. Twenty women underwent cesarean section due to cancer, combined with the Wertheim-Meigs procedure in six women. Sixteen women having stage IA1 cancer underwent conization as final treatment. Six women died of the disease. Liquid-based cytology samples were analysed for high-risk-HPV DNA genotype (an In-house real-time DNA PCR assay and the commercial Linear Array®), high-risk-HPV E6/E7 mRNA (a recently developed In-house real-time mRNA PCR assay and the commercial PreTectTM HPV-Proofer) and p16INK4a immunocytochemistry in pregnant women with normal cytology and atypical cytology. This study followed an initial study of different HR-HPV tests in mainly non-pregnant populations. In pregnant women stepwise logistic regression analysis showed that the p16 INK4a test and the In-house real-time mRNA PCR test were the most suitable tests in detecting high-grade lesions. In summary, 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 and analysis of p16 INK4a positivity and HR-HPV mRNA may be useful supplementary tests in pregnant populations with atypical cytology to accurately detect high-grade lesions. Investigation of atypical cytology during pregnancy with biopsy including large loop excisions is a safe procedure in regards to surgical complications and obstetrical outcome. There is a high rate of persistence and regression of dysplasia during pregnancy. Early detection of cervical cytological atypia and proper follow-up during pregnancy may lead to the detection of an increased proportion of stage I cancer, thereby avoiding radical operative procedures.
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| 5. |
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| 6. |
- Kärrberg, Cecilia, et al.
(författare)
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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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Ingår i: Acta obstetricia et gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349.
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Kärrberg, Cecilia, et al.
(författare)
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Support for down-staging of pregnancy-associated cervical cancer
- 2015
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Ingår i: Acta Obstetricia Et Gynecologica Scandinavica. - : Wiley. - 0001-6349. ; 94:6, s. 654-659
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo evaluate all cases of cervical cancer associated with pregnancy during 16years in the Western Region of Sweden. Setting and populationAll women with cervical cancer, diagnosed during pregnancy or within 6months after parturition, between 1993 and 2008. MethodsThe study was based on data from different registers and medical records. Main outcome measuresIncidence, diagnostic measures, treatment and outcome of disease. ResultsCervical cancer was diagnosed in 47 women (15.6/100000 deliveries). Sixteen women had abnormal vaginal bleeding and/or discharge. The other women were asymptomatic and diagnosed by abnormal cervical smear or clinical signs at vaginal examination. Nine women had atypical squamous cells of uncertain significance as presenting by cervical atypia. Twenty-two women had stage IA, 17 stage IB1, six stage IB2 and two stage IIA cancer. Cancer was diagnosed in the first trimester in two, in the second trimester in 14, in the third trimester in five and postpartum in 26 women. Histology revealed squamous cell carcinoma in 36 women, adenocarcinoma in eight, and adenosquamous carcinoma in three. Twenty women underwent cesarean section due to diagnosed or clinically suspected cancer, combined with the Wertheim-Meigs radical hysterectomy in six women. Sixteen women with stage IA1 cancer without signs of vascular invasion underwent conization as definitive therapy. Six women died of the disease. ConclusionEarly detection of cervical cytological atypia and proper follow-up during pregnancy led to detection of a high proportion of stage I cancer cases, which could be cured with fertility-sparing therapy.
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| 8. |
- Wiik, Johanna, et al.
(författare)
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Associations between cervical intraepithelial neoplasia during pregnancy, previous excisional treatment, cone-length and preterm delivery: a register-based study from western Sweden
- 2022
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Excisional treatment of cervical intraepithelial neoplasia (CIN) has been associated with increased risk of preterm delivery (PTD), although the underlying mechanism is as yet unclear. Studies on formalin-fixed excised tissue indicate that the risk increases with cone-length, but the magnitude of increase is uncertain, especially in case of minor excisions (≤10 mm), as well compared to women with untreated CIN during pregnancy. This study assesses the impact of cone-length at previous treatment for CIN as well as diagnosis of CIN during pregnancy on the risk of PTD. METHODS: A register-based cohort study in western Sweden linking cervical cytology, histology, and treatment data from the Swedish National Cervical Screening Registry to data on obstetric outcomes in singleton pregnancies 2008-2016 from the Swedish Medical Birth Registry. These groups were compared for PTD and other obstetric outcomes: (1) women with one excisional treatment (n=3250, including a subgroup (n=2408) with cone-length measured before fixation; (2) women with untreated CIN diagnosed during pregnancy (n=1380); and (3) women with normal cytology (n=42,398). Logistic regression analyses were adjusted for socioeconomic and health-related confounders. RESULTS: Treated women had increased risk of PTD (adjusted odds ratio (aOR) 1.60, 95% confidence interval (CI) 1.21-2.12), spontaneous PTD (aOR 1.95, 95% CI 1.40-2.72) and preterm prelabor rupture of membranes (pPROM) (aOR 2.74, 95% CI 1.66-4.51) compared to the CIN during pregnancy group. ORs were similar when compared to the normal cytology group. Risks of these outcomes increased with cone-length. Mean cone-length was 9.1 mm. Cone-length ≤10 mm was associated with increased risk of PTD (aOR 1.41, 95% CI 1.02-1.94), spontaneous PTD (aOR 1.73, 95% CI 1.18-2.54), and pPROM (aOR 2.44, 95% CI 1.40-4.28), compared to the CIN during pregnancy group. The PTD risk was similar for cone-lengths 3-10 mm, thereafter increasing by 15% with each additional millimeter. CONCLUSIONS: This study suggests that all excisional treatment, including small cones, are associated with increased risk of PTD and pPROM. Risks increase further with cone-length. In women of reproductive age, clinicians should aim to remove all CIN but minimal healthy cervical tissue. Cone-length should be recorded at treatment, for future prenatal risk estimation.
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| 9. |
- Wiik, Johanna, et al.
(författare)
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Associations of treated and untreated human papillomavirus infection with preterm delivery and neonatal mortality: A Swedish population-based study
- 2021
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 18:5
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Tidskriftsartikel (refereegranskat)abstract
- Background Treatment of cervical intraepithelial neoplasia (CIN) is associated with an increased risk of preterm delivery (PTD) although the exact pathomechanism is not yet understood. Women with untreated CIN also seem to have an increased risk of PTD. It is unclear whether this is attributable to human papillomavirus (HPV) infection or other factors. We aimed to investigate whether HPV infection shortly before or during pregnancyAU , as:well Hereandelsewhere as previous treat- ; IchangedHPVin ment for CIN, is associated with an increased risk of PTD and other adverse obstetric and neonatal outcomes. Methods and findings This was a retrospective population-based register study of women with singleton deliveries registered in the Swedish Medical Birth Register 1999–2016 (n = 1,044,023). The study population had a mean age of 30.2 years (SD 5.2) and a mean body mass index of 25.4 kg/m (SD 3.0), and 44% of the women were nulliparous before delivery. Study groups were defined based on cervical HPV tests, cytology, and histology, as registered in the Swedish National Cervical Screening Registry. Women with a history of exclusively normal cytology (n = 338,109) were compared to women with positive HPV tests (n = 2,550) or abnormal cytology (n = 11,727) within 6 months prior to conception or during the pregnancy, women treated for CIN3 before delivery (n = 23,185), and women with CIN2+ diagnosed after delivery (n = 33,760). Study groups were compared concerning obstetric and neonatal outcomes by logistic regression, and comparisons were adjusted for socioeconomic and health-related confounders. HPV infection was associated with PTD (adjusted odds ratio [aOR] 1.19, 95% CI 1.01–1.42, p = 0.042), preterm prelabor rupture of membranes (pPROM) (aOR 1.52, 95% CI 1.18–1.96, p < 0.001), prelabor rupture of membranes (PROM) (aOR 1.24, 95% CI 1.08–1.42, p = 0.002), and neonatal mortality (aOR 2.69, 95% CI 1.25–5.78, p = 0.011). Treatment for CIN was associated with PTD (aOR 1.85, 95% CI 1.76–1.95, p < 0.001), spontaneous PTD (aOR 2.06, 95% CI 1.95–2.17, p < 0.001), pPROM (aOR 2.36, 95% CI 2.19–2.54, p < 0.001), PROM (aOR 1.11, 95% CI 1.05–1.17, p < 0.001), intrauterine fetal death (aOR 1.35, 95% CI 1.05–1.72, p = 0.019), chorioamnionitis (aOR 2.75, 95% CI 2.33–3.23, p < 0.001), intrapartum fever (aOR 1.24, 95% CI 1.07–1.44, p = 0.003), neonatal sepsis (aOR 1.55, 95% CI 1.37–1.75, p < 0.001), and neonatal mortality (aOR 1.79, 95% CI 1.30–2.45, p < 0.001). Women with CIN2+ diagnosed within 3 years after delivery had increased PTD risk (aOR 1.18, 95% CI 1.10–1.27, p < 0.001). Limitations of the study include the retrospective design and the fact that because HPV test results only became available in 2007, abnormal cytology was used as a proxy for HPV infection. Conclusions In this study, we found that HPV infection shortly before or during pregnancy was associated with PTD, pPROM, PROM, and neonatal mortality. Previous treatment for CIN was associated with even greater risks for PTD and pPROM and was also associated with PROM, neonatal mortality, and maternal and neonatal infectious complications.
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