A randomized trial of basing treatment on human papillomavirus and/or cytology results in low-grade cervical lesion triage.

OBJECTIVE: This study was undertaken to compare management algorithms that base treatment with loop electrosurgical excision procedure on human papillomavirus and/or repeat Papanicolaou test smear results. STUDY DESIGN: A randomized trial that referred 674 women with either atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions cytology results, detected in organized screening to treatment either (1) if they were positive in a repeat Papanicolaou test smear and/or a human papillomavirus test or (2) if they were positive in the repeat Papanicolaou test smear test only. Women who tested positive were treated, regardless of colposcopic findings. RESULTS: There were 208 of 337 (62%) women who were treated in the human papillomavirus /Papanicolaou test smear group (187/337 because of HPV positivity) and 138 of 337 (41%) in the Papanicolaou test smear only group. Histopathologically diagnosed cervical intraepithelial neoplasia grade 2 or worse was found among 112 of 337 (33.2%) women in the human papillomavirus/Papanicolaou test smear group compared with 85 of 337 (25.2%) women in the Papanicolaou test smear only group (P < .05). Twenty-one women with cervical intraepithelial neoplasia 2+ had normal colposcopy. CONCLUSION: For adequate cervical intraepithelial neoplasia 2+ sensitivity, the decision to use loop electrosurgical excision procedure needs to be based on human papillomavirus testing results and should not exclude women with normal colposcopy.

Does HPV-status 6-12 months after treatment of high grade dysplasia in the uterine cervix predict long term recurrence?

BACKGROUND: Women once treated for high grade cervical dysplasia have a high long term risk for developing new dysplasia or cancer. OBJECTIVES: To investigate if human papilloma virus (HPV)-negativity after treatment of cervical dysplasia reduces the need for frequent long term follow up. DESIGN: Case/control study based on archival smears. METHODS: Women with cervical intraepithelial neoplasi (CIN)2-3, treated for dysplasia and with recurrence of CIN2+ more than 2 years after treatment were compared with controls without recurrence, matched for age and date of treatment. High risk-HPV-DNA were analysed with PCR from two archival smears per woman. Mean follow up time was 14.6 years. RESULTS: 24% (45/189) of cases and 11% (43/378) of controls were HPV-positive in any of two smears. Odds ratio (OR)=2.5 (1.6-3.8). CONCLUSION: HPV-status 6-12 months after treatment of high grade dysplasia is of limited value for the design of long term follow up.

Effect of Fee on Cervical Cancer Screening Attendance--ScreenFee, a Swedish Population-Based Randomised Trial.

BACKGROUND: Attendance in the cervical cancer screening programme is one of the most important factors to lower the risk of contracting the disease. Attendance rates are often low in areas with low socioeconomic status. Charging a fee for screening might possibly decrease attendance in this population. Screening programme coverage is low in low socio-economic status areas in Gothenburg, Sweden, but has increased slightly after multiple interventions in recent years. For many years, women in the region have paid a fee for screening. We studied the effect of abolishing this fee in a trial emanating from the regular cervical cancer screening programme. METHOD: Individually randomised controlled trial. All 3 124 women in three low-resource areas in Gothenburg, due for screening during the study period, were randomised to receive an offer of a free test or the standard invitation stating the regular fee of 100 SEK (≈11 €). The study was conducted during the first six months of 2013. Attendance was defined as a registered Pap smear within 90 days from the date the invitation was sent out. RESULTS: Attendance did not differ significantly between women who were charged and those offered free screening (RR 0.93; CI 0.85-1.02). No differences were found within the districts or as an effect of age, attendance after the most recent previous invitation or previous experience of smear taking. CONCLUSION: Abolishment of a modest screening fee in socially disadvantaged urban districts with low coverage, after previous multiple systematic interventions, does not increase attendance in the short term. Other interventions might be more important for increasing attendance in low socio-economic status areas. TRIAL REGISTRATION: ClinicalTrials.gov NCT02378324.

[Increasing number of Chlamydia infections--how can we reverse this trend?]. / Klamydiainfektionerna ökar--hur vänder vi trenden?

The incidence of chlamydia in Göteborg, the second largest city in Sweden, increased by 81 percent between 1995 and 2001. The majority (82%) of men and women diagnosed with chlamydia were aged 15-29 years. The incidence of chlamydia was higher among teenagers from areas of lower socio-economic index during the first years of the study but after 1995 there was no difference between low and high socio-economic groups. Chlamydia tests were taken three times more often in women than men. Analysis of original data from the Swedish survey of sexual behaviour 1996 demonstrated a strong correlation between the number of sexual partners and STD. Strategies for preventing the spread of chlamydia should be to a greater extent directed towards men and include better accessibility for men to STD clinics as well as a general improvement in contact tracing. The general public should be informed about the fact that chlamydia infections do not always give symptoms and may lead to infertility. Campaigns about condom use in order to avoid chlamydia, HIV-infection and other STD are needed.

Contraceptive use and pregnancy outcome in three generations of Swedish female teenagers from the same urban population.

BACKGROUND: The primary objective of the study was to describe contraceptive use, reasons for discontinuation of contraception and pregnancy outcome in three generations of female teenagers over a period of 20 years. The secondary objective was to describe the relationship between contraception, smoking, body mass index (BMI) and socioeconomic status (SES). STUDY DESIGN: A cross-sectional comparison of 19-year-old women born in 1962, 1972 and 1982 and living in the city of Gothenburg, Sweden, in 1981, 1991 and 2001 was conducted. Contraceptive use, pregnancy outcome, smoking and weight/height were assessed by a postal questionnaire. RESULTS: Current contraceptive use was unchanged between the 62 (60%) and 72 cohorts (62%) but had increased (p<.01) in the 82 cohort (78%); there was no difference in contraceptive use between SES groups at any time. Condom use alone increased over time (p<.01), and the use of oral contraception and a condom together had increased in the 72 and 82 cohorts compared to the 62 cohort (p<.01). Reasons given for using and discontinuing oral contraceptives in three generations of teenagers were studied over 20 years. In addition to contraception, oral contraception was used to reduce dysmenorrhea and heavy bleeding. Discontinuation due to bleeding disturbances decreased (p<.01) over time, whereas discontinuation due to mental side effects increased (p<.01). The percentage of women who had been pregnant at < or =19 years of age in the 82 cohort (7%) was lower (p<.01) than in the 1962 (11%) and 1972 (13%) cohorts. However, there was a successive increase (p<.001) in the percentage of women who had been pregnant more than once at < or =19 years of age (1962/1972/1982: pregnant more than once, 8%/21%/31%). Smoking decreased over time (p<.01) and was no longer related to SES in the 82 cohort. BMI increased (p<.01) over time. There was no difference in BMI between SES groups in the 62 and 72 cohorts but was higher in the low-SES group in the 82 cohort compared to the middle (p<.01) and high (p<.05) SES groups. CONCLUSIONS: Contraceptive use was higher in the 82 cohort where there was a corresponding reduction in the percentage of women who had been pregnant at < or =19 years of age compared with the 62 and 72 cohorts. Discontinuation of oral contraception due to mental side effects increased over time. The prevalence of smoking decreased and BMI increased, and there were changes in smoking prevalence and BMI in the different SES groups over time.

The cervical cancer screening program from a midwife's perspective.

BACKGROUND: Midwives in Sweden are responsible for taking Papanicolaou (Pap) smears as part of the cervical cancer screening program. The aim of this study was to investigate midwives knowledge, experience and management of the cervical cancer screening program, and their apprehension of women's knowledge about Pap-smear screening. METHODS: A postal questionnaire was sent to midwives working in primary health care in 3 different areas in Sweden. A total of 156 (77%) out of 201 midwives completed the questionnaire. RESULTS: Four of 5 midwives considered themselves to have the education they needed to manage the screening program. However, the study indicated that midwives lacked a basic structure when giving information. As many as every third midwife refrained from or had an irrelevant answer to the proposed question, what is meant by a cellular atypia? Almost all midwives saw themselves as the main informant about Pap-smear screening. At the same time, the midwives perceived that women lacked knowledge about cellular atypia, and thought it was the same as cancer. Some 38% of the midwives expressed a wish to terminate the 'assembly line-like' screening system. The remaining midwives were completely satisfied with the organisation. CONCLUSIONS: Many midwives lacked time and a structured guidance when discussing screening and cervical atypia. Improvement in the organisation and certified education for Pap-smear screening with access to recent research, could develop a more empowering exchange between the midwives and the women participating in cervical screening.

Long term risk of invasive cancer after treatment for cervical intraepithelial neoplasia grade 3: population based cohort study.

OBJECTIVE: To study the long term risk of invasive cancer of the cervix or vagina after treatment for cervical intraepithelial neoplasia grade 3. DESIGN: Prospective cohort study. SETTING: Swedish cancer registry. PARTICIPANTS: All women in Sweden with severe dysplasia or cervical carcinoma in situ (equivalent to cervical intraepithelial neoplasia grade 3) treated during 1958-2002 (n=132,493) contributing 2,315,724 woman years. MAIN OUTCOME MEASURES: Standardised incidence ratios with risk of cancer in the Swedish general female population as reference, and relative risks in multivariable log-linear regression model, with internal references. RESULTS: Women with previous cervical intraepithelial neoplasia grade 3 had an increased risk of invasive cervical cancer compared with the general female population (standardised incidence ratio 2.34, 95% confidence interval 2.18 to 2.50). The increased risk showed a decreasing trend with time since diagnosis for women treated later than 1970 but the risk was still increased after 25 years. An effect of age was found, with an accentuated increase in risk for women aged more than 50. The excess risk for cervical cancer associated with previous cervical intraepithelial neoplasia grade 3 has steadily increased since 1958. For vaginal cancer the standardised incidence ratio was 6.82 (5.61 to 8.21) but this decreased to 2.65 after 25 years. Adjustments in the multivariable log-linear regression model did not substantially alter these results. CONCLUSIONS: Women previously treated for cervical intraepithelial neoplasia grade 3 are at an increased risk of developing invasive cervical cancer and vaginal cancer. This risk has increased since the 1960s and is accentuated in women aged more than 50. The risk is still increased 25 years after treatment.

Liquid-based cytology versus conventional Papanicolaou smear in an organized screening program : a prospective randomized study.

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.

Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle (VLP) vaccine.

BACKGROUND: The duration of protection afforded by vaccines represents a critical test of their utility as public health interventions. Some vaccines induce long-term immunity, while others require booster doses. Vaccines that induce long-term protection are usually characterized by the generation of immune memory. Recent trials of a quadrivalent (types 6, 11, 16, 18) human papillomavirus (HPV) vaccine have demonstrated high efficacy through 5 years of follow-up. We evaluated the extent to which the vaccine is able to generate HPV type-specific immune memory. METHODS: A total of 552, 16-23-year-old women were enrolled in a double-blind, placebo-controlled study. At enrollment, subjects were randomized in a 1:1 ratio to receive three-dose regimens of quadrivalent HPV vaccine or placebo with 3 years' follow-up. A subset of 241 subjects (n=114 in the quadrivalent HPV vaccine group and n=127 in the placebo group) underwent 2 further years of follow-up. All extension subjects received quadrivalent HPV vaccine at month 60 to examine the extent of immune memory in response to the primary vaccination series. RESULTS: Serum anti-HPV levels declined post-vaccination, but reached a plateau at month 24 that remained stable through month 60. Administration of a challenge dose of vaccine induced a classic anamnestic response, with anti-HPV levels 1 week post-challenge reaching levels observed 1 month following the completion of the three-dose primary series. At 1 month post-challenge, anti-HPV responses were higher than those observed 1-month post-dose 3. DISCUSSION: A three-dose regimen of quadrivalent HPV vaccine induces high efficacy and stable anti-HPV levels for at least 5 years. Vaccination also induces robust immune memory. These findings suggest that the efficacy of this vaccine will be long lasting.

Cervical cancer screening--"For better or worse...": women's experience of screening.

In Sweden, the population-based cervical cancer screening program has been in progress since the 1970s and is directed toward women between 23 and 60 years of age. The aim of this study was to explore women's experience of cervical screening after being diagnosed with cancer. A qualitative study inspired by Grounded Theory was used. Eleven women were interviewed. The interviews were analyzed using the constant comparative method. "Screening-For Better or Worse..." was identified as the core category, around which the categories "Unawareness," "Trust," "Search for Understanding," and "Making the Invisible Visible" were integrated and on which the conceptual model was built. The experience of screening had both a positive and a negative dimension for the women stricken by cervical cancer. The women had a positive experience of screening as such and they believed in its benefits. However, many women felt deceived and, because of their unawareness, questions arose for which they searched for understanding. The women requested adequate and understandable information. Their trust remained because the contact with healthcare professionals involved in screening and in the follow-up program had been reassuring.

Women's experience of coping with a positive Pap smear: A register-based study of women with two consecutive Pap smears reported as CIN 1.

BACKGROUND: In Sweden approximately 40 000 women receive information annually that their Papanicolaou (Pap) smear test showed dysplasia and about 400 women are diagnosed with invasive cervical cancer. The aim of this study was to evaluate women 5 years after two consecutive Pap smears diagnosed with mild dysplasia (CIN 1), by describing their experience of receiving information about the results of the smear and how examinations, treatment and follow-up had affected them. METHODS: A questionnaire was sent in 1999 to 329 women who according to the Department of Clinical Pathology, Karlstad, had two consecutive Pap smears reported as mild dysplasia (CIN 1) during 1993 and who as a result of this finding should have undergone colposcopy and biopsy according to an agreed general program. RESULTS: The questionnaire was completed by 242 women (74%). The finding of mild dysplasia was obtained at a screening test in 95%, and 96% reported that they had participated in the follow-up program. One hundred and eighty-four women (76%) experienced follow-up in a positive way. Seventy-two percent considered they understood the meaning and consequences of having mild dysplasia. Nevertheless, feelings of worry and anxiety affected 59%. For 30% it affected everyday life between being informed of the result of the first Pap smear test and subsequent further investigation. Twenty women (8%) reported a remaining negative influence on sexuality and their experience of sexual intercourse as a consequence of the management of mild dysplasia. This finding was correlated with less satisfaction with follow-up and a negative influence on self-esteem. CONCLUSION: Women felt vulnerable when being investigated for intraepithelial neoplasia, but this did not influence willingness to participate in follow-up. The discovery created unnecessary worry and a negative experience that may be solved by a better-developed educational program at the time of screening. There were no signs of remaining anxiety 5 years later, but 8% of women reported a remaining negative influence on their sexual life.

Knowledge and attitudes about the Pap-smear screening program: a population-based study of women aged 20-59 years.

BACKGROUND: The aim of the Papanicolau (Pap)-smear screening program is to reduce morbidity and mortality resulting from cervix cancer. Compliance to screening has previously been suggested to be associated with women's knowledge. The aim of this study was to investigate knowledge about and attitudes to gynecologic Pap-smear screening among women in a Swedish region where a screening program has been in existence since 1970. MATERIAL AND METHODS: Questionnaires were mailed to a random sample of 400 women born 1940-79. Replies were received from 275 of the 392 (70%) available for evaluation. RESULTS: Ninety-five percent of the responders had a registered Pap smear in the pathology database. Women's knowledge and concerns were age-dependent. Ninety-five percent stated that they knew the purpose of screening but only 62% could indicate which type of cancer the screening actually examined. The majority (82%) did not experience anxiety while awaiting the test result. Almost all women knew that dysplasia may not give symptoms but 10% did not consider seeking a doctor when experiencing postcoital bleeding. Fifty percent thought that their life-style may be of importance for developing dysplasia but only 13% were aware of the protective effect of a condom. CONCLUSION: Although the vast majority of the women had experience of participating in the screening program, one in three of the women were unaware of which type of cancer she was being screened for and only half of the women were aware of the connection between dysplasia/cervix cancer and life-style factors. It is particularly important to provide better information about life-style factors in order to give women the opportunity of acting accordingly.