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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.

Background Screening for cervical cancer based on testing for human papillomavirus (HPV) increases the sensitivity of detection of high-grade (grade 2 or 3) cervical intraepithelial neoplasia, but whether this gain represents overdiagnosis or protection against future high-grade cervical epithelial neoplasia or cervical cancer is unknown. Methods In a population-based screening program in Sweden, 12,527 women 32 to 38 years of age were randomly assigned at a 1:1 ratio to have an HPV test plus a Papanicolaou (Pap) test (intervention group) or a Pap test alone (control group). Women with a positive HPV test and a normal Pap test result were offered a second HPV test at least 1 year later, and those who were found to be persistently infected with the same high-risk type of HPV were then offered colposcopy with cervical biopsy. A similar number of double-blinded Pap smears and colposcopies with biopsy were performed in randomly selected women in the control group. Comprehensive registry data were used to follow the women for a mean of 4.1 years. The relative rates of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected at enrollment and at subsequent screening examinations were calculated. Results At enrollment, the proportion of women in the intervention group who were found to have lesions of grade 2 or 3 cervical intraepithelial neoplasia or cancer was 51% greater (95% confidence interval [CI], 13 to 102) than the proportion of women in the control group who were found to have such lesions. At subsequent screening examinations, the proportion of women in the intervention group who were found to have grade 2 or 3 lesions or cancer was 42% less (95% CI, 4 to 64) and the proportion with grade 3 lesions or cancer was 47% less (95% CI, 2 to 71) than the proportions of control women who were found to have such lesions. Women with persistent HPV infection remained at high risk for grade 2 or 3 lesions or cancer after referral for colposcopy. Conclusions The addition of an HPV test to the Pap test to screen women in their mid-30s for cervical cancer reduces the incidence of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected by subsequent screening examinations.

Objective. To construct a simple scoring system for colposcopic examination that can facilitate education of colposcopists and increase the accuracy of evaluation. Design. Prospective clinical study. Setting and population. Two hundred ninety-seven examinations of women referred for colposcopy in western Sweden. Methods. Five variables were scored: acetowhiteness, margins and surface, vessels, lesion size, and iodine staining. Each variable could be assigned one of three ordered values. Multiple logistic regression was used in order to assess the ability of each single score to predict high-grade lesions (HGL) in histology (cone or biopsy). Main outcome measures. Histopathology. Results. All five variables independently predicted for HGL. The analysis resulted in an 'ideal' weighted scoring system, which showed good sensitivity and specificity. Rounding off of each weight gave a more useful and simpler scoring system with values of 0, 1, or 2 without any significant change in performance. The possible tot...

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%.

Objective To evaluate all cases of cervical cancer associated with pregnancy during 16 years in the Western Region of Sweden. Design Retrospective, descriptive cohort study. Setting and population All women with cervical cancer, diagnosed during pregnancy or within 6 months after parturition, between 1993 and 2008. Methods The study was based on data from different registers and medical records. Main outcome measures Incidence, diagnostic measures, treatment and outcome of disease. Results Cervical cancer was diagnosed in 47 women (15.6/100 000 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. Conclusion Early 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.

Screening for cervical cancer by testing for human papillomavirus (HPV), the major cause of the disease, reportedly increases the sensitivity of detecting high-grade (grade 2 or 3) cervical intraepithelial neoplasia (CIN). It is not clear, however, whether this reflects protection against future high-grade CIN or cervical cancer, or whether it represents over-diagnosis. This Swedish population-based screening program randomly assigned 12,527 women ranging in age from 32 to 38 years to have either an HPV test plus a Pap test (n = 6257, the intervention group) or a Pap test alone (n = 6270, the control group). Those having a positive HPV test and a normal Pap test were offered a second HPV test at least 1 year later, and those persistently infected with the same high-risk type of HPV were offered colposcopy with cervical biopsy. A similar number of double-blinded Pap smears and colposcopies with biopsy were done in randomly selected control women to avoid ascertainment bias. The average follow-up interval was 4.1 years. Initially, 51% more women in the intervention group than in the control group had grade 2 or 3 CIN or cancer. On subsequent screening, the proportion of women in the intervention group who had grade 2/3 lesions or cancer was 42% less, and the proportion with grade 3 lesions or cancer was 47% less than the proportion of control women having such lesions. The increased incidence of grade 2 lesions found at initial screening in the intervention group was not followed by a significant reduction of such lesions at later screening. Women with persistent HPV infection remained at high risk of grade 2 or 3 lesions or cancer after being referred for colposcopy. Five women in the control group and one in the intervention group were found to have invasive squamous-cell carcinoma. Four in each group developed adenocarcinoma in situ or adenocarcinoma. All of these women with advanced changes were HPV-positive at baseline. The improved sensitivity of HPV testing in women in their mid-30s who are screened for cervical cancer is not solely a result of over-diagnosis. It can be ascribed-at least in part-to the earlier diagnosis of cervical lesions that do not regress on follow-up screening.

Objective To evaluate whether colposcopically directed cervical biopsies during pregnancy are associated with surgical/obstetric complications and to examine the natural course (regression, persistence, progression) of dysplasia during pregnancy. Design Prospective clinical study. Setting and population University Hospital and 251 pregnant women with atypical cervical cytology in early pregnancy. Methods The patients were investigated by colposcopically directed punch biopsies, colposcopically directed loop-biopsies or LEEP-cones. The histology results during pregnancy were compared with those after delivery to evaluate the natural course of dysplastic lesions during pregnancies. Postoperative complications were recorded. Obstetric outcome was recorded and compared with the 54 919 other births in the same geographical area during the study period. Main outcome measures Persistence, regression and progression of cervical dysplasia, surgical complications after diagnostic procedure, incidence of preterm birth, mode of delivery. Results 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 and the miscarriage rate was low (0.8%). There were no differences in mode of delivery, preterm birth or other obstetrical variables between the study group and the large control cohort. Conclusion Investigation of atypical cytology during pregnancy with biopsy including large loop excisions is a safe procedure with regard to surgical complications and obstetrical outcome. There is a high rate of persistence and regression of dysplasia during pregnancy.

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.Prospective clinical study.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.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.Colposcopic score (Swede score) and histology (CIN1, 2, 3; AIS; cancer).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.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.

BACKGROUND: 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. METHODS: We used the database from the intervention arm (n = 6,257 women) of a population-based randomized trial of double screening with cytology and HPV DNA testing to evaluate the efficacy of 11 possible cervical screening strategies that are based on HPV DNA testing alone, cytology alone, and HPV DNA testing combined with cytology among women aged 32-38 years. The main outcome measures were sensitivity for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) within 6 months of enrollment or at colposcopy for women with a persistent type-specific HPV infection and the number of screening tests and positive predictive value (PPV) for each screening strategy. All statistical tests were two-sided. RESULTS: Compared with screening by cytology alone, double testing with cytology and for type-specific HPV persistence resulted in a 35% (95% confidence interval [CI] = 15% to 60%) increase in sensitivity to detect CIN3+, without a statistically significant reduction in the PPV (relative PPV = 0.76, 95% CI = 0.52 to 1.10), but with more than twice as many screening tests needed. Several strategies that incorporated screening for high-risk HPV subtypes were explored, but they resulted in reduced PPV compared with cytology. Compared with cytology, primary screening with HPV DNA testing followed by cytological triage and repeat HPV DNA testing of HPV DNA-positive women with normal cytology increased the CIN3+ sensitivity by 30% (95% CI = 9% to 54%), maintained a high PPV (relative PPV = 0.87, 95% CI = 0.60 to 1.26), and resulted in a mere 12% increase in the number of screening tests (from 6,257 to 7,019 tests). CONCLUSIONS: Primary HPV DNA-based screening with cytology triage and repeat HPV DNA testing of cytology-negative women appears to be the most feasible cervical screening strategy.

BACKGROUND. The objective of this study was to evaluate whether liquid-based cytology (LBC) can improve high-standard cervical cancer screening cytology further. The primary endpoint was histopathologic high-grade lesions in current and subsequent screening rounds. The secondary endpoints were cytologic diagnosis and inadequate samples. METHODS. Women were randomized to smear taking by conventional Papanicolaou (Pap) smear or LBC according to the time of appointment. Eight thousand eight hundred ten conventional Pap smears and 4674 LBC samples were included. Evaluations of atypical cytology and referral to colposcopy and treatment were performed as routine procedures. Histopathologic diagnoses were retrieved from a regional database 8 months after the study was closed. The mean follow-up was 2 years and 9 months. RESULTS. Inadequate samples were observed in 0.3% of LBC samples versus 0.7% of Pap smears (P = .002). The total fraction of nonbenign diagnoses in cytology was 4.5% versus 3.5%, respectively (P < .001). Histopathologic evaluation was made on 570 patients constituting 4.6% of the LBC samples and 4% of the Pap smears. Forty percent more high-grade lesions were identified as a result of LBC sampling (1.20% vs 0.85%; P = .05). The influence of the sampling method was significant for all variables (odds ratio [OR], 1.60; 95% confidence interval [95% CI], 1.12–2.28) for high-grade lesions that were identified by histology when adjusting for age and screening unit in a logistic regression model. At the second follow-up 2 years and 1 month later, the OR was decreased only slightly (1.51; 95% CI, 1.13–2.01). CONCLUSIONS. In the ongoing cervical screening program of western Sweden, liquid cytology produced a significantly higher yield of histologic high-grade lesions compared with conventional Pap smears. Cancer (Cancer Cytopathol) 2007. © 2007 American Cancer Society.

This article describes the development of a simple scoring system for colposcopic grading of high-grade cervical dysplasia. Two different clinic populations with a 48% and a 35% rate of high-risk lesions were used to develop the model, which was based on data accumulated from March 2001 to June 2003 during colposcopic examination of women referred for abnormal cytology. Colposcopically directed biopsies were taken of all suspicious areas using punch biopsy, laser cone, or large loop excision of the transformations zone (LLETZ). Only patients with histopathology of the cervix were included in the study (n = 297). All colposcopic examinations were graded by experienced colposcopists for acetowhiteness of the epithelium, lesion margin and surface contour, vessel pattern, lesion size, and iodine staining. A three-point scoring system was used for each colposcopic characteristic (see Table 1). Benign conditions were seen in 30% of the histopathologic samples, and koilocytosis or cervical intraepithelial neoplasia (CIN 1) was diagnosed in 25%. Forty-four percent of the samples contained high-grade lesions, including cervical intraepithelial neoplasia (CIN) 2 (13%), CIN 3 (28%), and invasive cancer (3%). Using the biopsy diagnosis of high-grade CIN (defined as CIN 2 or greater) as a standard, an "ideal" grading system was constructed that assigned each colposcopic characteristic a weighted value that would produce the best sensitivity and specificity performance for the model. These values were then rounded off to simplify the final grading system shown in Table 1. When the colposcopic lesion characteristics were analyzed by multiple logistic regression, acetowhiteness had the highest correlation to high-grade dysplasia, followed by lesion margin and surface contour, lesion size, iodine staining, and vessel pattern. The distribution of total colposcopic scores for each lesion was then analyzed for the sensitivity and specificity to predict a CIN 2 lesion or greater. No patient with CIN 2 had a colposcopic score of four or less. Only two patients had a score of five. Ninety-five percent of the patients with CIN 2 or greater had a colposcopic score of six or higher. Only 10% of women with CIN 1 or less had a colposcopic score of eight or more. Four women in the series had glandular dysplasia and received scores of eight to 10. All had adenocarcinoma in situ on final histologic evaluation. There were 10 invasive cancers diagnosed. Five women had squamous cell carcinoma, four had adenocarcinoma, and one had a mixed adenosquamous carcinoma. The colposcopic scoring index graded one of these patients with seven points; the other nine received scores of eight to 10. As a control, another 199 women patients were diagnosed with benign, low-grade, or high-grade cervical dysplasia based on the general colposcopic impression of the experienced examiner without using any formal grading system. Eighteen of 85 biopsy-proven high-grade lesions were underdiagnosed by colposcopic impression and six of 114 low-grade lesions were misidentified as high-grade (sensitivity = 79% and specificity = 95%).

alpha 2-Antiplasmin and alpha 2-macroglobulin have been studied during the menstrual cycle, pregnancy and parturition in healthy women, and during use of various types of contraception in both healthy and diabetic women, and compared with a reference group of healthy men and women. alpha 2-Antiplasmin showed a slight sex difference, with higher values in women. The luteal phase of the menstrual cycle showed slightly higher values than the other phases. alpha 2-Antiplasmin increased during pregnancy, decreased (probably due to consumption) during labor and increased again in the puerperium. Treatment with neither combined contraceptive pills nor low dose progestogen pills gave any changes in alpha 2-antiplasmin. alpha 2-Macroglobulin showed low values during menstruation. The increase during pregnancy and treatment with combined contraceptive pills is in accordance with earlier findings. It is concluded that synthesis and metabolism of alpha 2-antiplasmin are under hormonal influence. The role of alpha 2-antiplasmin in the decreased fibrinolysis in pregnancy is discussed.

Twenty-three young women with insulin-dependent diabetes were randomly allocated to contraceptive treatment with either a progestogen only (Lynestrenol 0.5 mg) (LYN) or a combined oral contraceptive (OC) (ethinyl estradiol 50 micrograms + lynestrenol 2.5 micrograms) (EE + LYN). After six months treatment the medication was withdrawn for at least two months, after which the patients were placed on the other preparation. Diabetes control and serum and high density lipoprotein (HDL) lipids were assessed before and after 1, 3 and 6 months of treatment. Low-dose LYN administration did not alter the insulin requirement, blood glucose or body weight while the combined EE + LYN treatment increased the insulin requirement (p less than 0.01) without altering blood glucose or body weight. Low-dose LYN reduced serum triglycerides (p less than 0.001), serum cholesterol (p less than 0.001) and serum phospholipids (p less than 0.01) without affecting HDL lipids, while EE + LYN gave an inconsistent increase in serum triglycerides (p less than 0.01) but no change in HDL lipids. These findings confirm our earlier results and we conclude that EE + LYN influences diabetes control slightly more (although still not seriously) than the low-dose LYN. It is suggested that insulin-dependent diabetics (in contrast to non-diabetics) are more sensitive to the influence of 19-norprogestogens than to alkylated estrogens, with respect to lipid metabolism.

Thirtyeight women with insulin-dependent diabetes were randomly allocated to contraception with either a progestogen only (Lynestrenol 0.5 mg daily) (LYN), a combined oral contraceptive (OC) (Ethinyl oestradiol 50 μg + Lynestrenol 2.5 mg) (EE + LYN) or a non-hormonal intrauterine device (IUD). Diabetes control (i.e. insulin dosage, blood and urinary glucose and body weight) and the lipid concentration in serum and in high density lipoprotein (HDL) were assessed before and during six months use of the respective contraceptives. In the LYN group urinary glucose excretion increased 10% in spite of unchanged blood glucose, body weight and insulin requirement. All serum lipids decreased; triglycerides by 40% (P < 0.01), cholesterol by 13% (P < 0.01) and phospholipids by 12% (P = 0.06), without alteration of HDL lipids. In the group using combined OC (EE + LYN) the insulin requirement increased by 7% (P < 0.01) without any change in body weight or blood and urinary glucose. Serum as well as HDL lipids remained unchanged. In the IUD group neither diabetes control nor serum or HDL lipids were altered. It is concluded that in insulin-dependent diabetics the progestogen (LYN) has little influence on diabetes control but has a marked, though probably not adverse, effect on lipid metabolism. The combined OC (EE + LYN) may impair glucose homeostasis slightly but has little influence on serum or HDL lipids. These findings seem to differ from those obtained in non-diabetics during administration of contraceptive steroids and these differences suggest that absence of endogenous insulin production enhances the effects of progestogen and reduces the effects of synthetic oestrogens on lipid metabolism.

Triglycerides, cholesterol and phospholipids in serum and high density lipoproteins (HDL) were assessed in 11 women with previous gestational diabetes before and repeatedly during 6 months of low dose progestogen (lynoestrenol = LYN) contraceptive administration. Eight of these women also were followed in an identical manner during non-hormonal contraception (IUD) and 6 of them during combined oral contraceptive administration (EE + LYN). During the use of IUD or LYN administration neither serum nor HDL lipids changed. The combined OC, EE + LYN, increased serum triglycerides progressively: 73% (P less than 0.01) after 6 months concomitant with a 100%-increment of HDL triglycerides (P less than 0.01) HDL-cholesterol and -phospholipids were not consistently changed. The EE + LYN induced alterations differed from the effects of LYN alone (P less than 0.01). During the use of IUD or LYN administration neither serum nor HDL lipids changed. The combined OC, EE + LYN, increased serum triglycerides progressively: 73% (P less than 0.01) after 6 months concomitant with a 100%-increment of HDL triglycerides (P less than 0.01). HDL-cholesterol and -phospholipids were not consistently changed. The EE + LYN induced alterations differed from the effects of LYN alone (P less than 0.01). These results suggest that low dose progestogens, such as LYN, could be considered as contraceptive alternatives in women with gestational diabetes. However, combined OC should be avoided in these patients. The present findings differ from those obtained in insulin-dependent diabetics and suggest that a diabetic prediposition enhances the effects of synthetic oestrogens and/or diminishes some of the effects of progestogens on lipid metabolism.

Intravenous glucose tolerance tests (IVGTT) with simultaneous assessment of plasma insulin and analyses of the fatty acid composition of serum lecithin and cholesterol esters were performed in 11 women with previous gestational diabetes before and repeatedly during 6 months' administration of a low-dose progesterone (lynestrenol = LYN). 8 of these women were also followed in an identical manner during 6 months of nonhormonal contraception (intrauterine device = IUD) and additionally 6 of these women were followed also during the use of a combined oral contraceptive (OC) (ethinyl estradiol + lynestrenol - EE + LYN). LYN did not alter the IVGTT or plasma insulin but decreased the proportion of polyunsaturated fatty acids (PUFA) in serum lecithin (p less than 0.01) and cholesterol esters (p less than 0.01) where oleic acid was reciprocally increased (p less than 0.05). After 6 months' use of IUD, on the other hand, the k value of IVGTT increased by 45% (p less than 0.01) without significant changes in plasma insulin. In both lecithin and cholesterol ester PUFA increased (p less than 0.05) and cholesterol ester oleate decreased (p less than 0.01); i.e., virtually the reversal of the changes seen during LYN administration. The combined OC, EE + LYN, caused a decrease in the k value by 27% (p less than 0.05) which was apparent even when compared to the effects of LYN alone. EE + LYN also increased (p less than 0.05) lecithin palmitate and decreased stearate (p less than 0.05) and had a concomitant tendency to lower PUFA and increase oleic acid in both lecithin and cholesterol esters. These results indicate that LYN has little influence on the glucose tolerance in women predisposed to diabetes but may provide poorer conditions for dietary treatment of subclinical diabetes than do nonhormonal IUDs. The combined CO, EE + LYN, on the other hand, promptly diminishes glucose tolerance and may also have an unfavorable influence on liver metabolism.