Key words: HPV; human papillomavirus; DNA; mRNA; PreTect HPV-Proofer; NASBA; PCR; ASCUS; LSIL Cytological cervical cancer screening programs have been successful in reducing the incidence of cervical cancer, even though a single conventional Papanicolaou (Pap) smear is only moderately accurate and does not achieve concurrent high sensitivity and specificity. 1,2 The management of women with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) is problematic because only a small proportion will progress to cervical intraepithelial neoplasia (CIN) 3 and invasive cervical carcinoma (ICC). Histologically verified CIN has been found in 10 -60% of women with an ASCUS diagnosis, with CIN2/3 present in more than 5%. 3-11 Pap smear follow-up of women with an ASCUS smear fails to identify all women at higher risk of CIN2ϩ, suggesting that cervical cancer screening programs might benefit from implementing new diagnostic tests in the triage of women with equivocal Pap smears. 12 Infection with high-risk (HR) types of HPV is necessary for the development of ICC 13-16 and the expression of the E6/E7 oncogenes is necessary for conversion to and maintenance of malignancy in cervical tissue. [17][18][19] Therefore, detection of the E6/E7 mRNA of HR-HPV types might serve as a better risk evaluation factor than mere DNA detection for the development of high-grade squamous intraepithelial lesion (HSIL) and ICC. 20 The combination of cytology and HPV testing seems to save additional life at a reasonable cost compared to Pap testing alone. 21,22 Detection of E6/E7 mRNA can be achieved by using the commercial PreTect HPV-Proofer assay (NorChip AS, Klokkarstua, Norway), that utilizes nucleic acid sequence based amplification (NASBA).The aim of our study was to assess whether a positive HPV mRNA or DNA test at the time of an ASCUS or LSIL Pap-smear identifies women diagnosed with a histological CIN2ϩ after 2 years of follow-up. Material and methods Study subjectsThe study subjects comprise a subgroup from 4,136 women older than 30 years of age that visited a selection of gynecologists in Oslo, Norway, and have been tested in 2001 for the presence of HPV DNA by Gp5ϩ/6ϩ consensus PCR and E6/E7 transcripts by real-time multiplex NASBA (PreTect HPV-Proofer, NorChip AS) in addition to cytology. 35 PreTect HPV-Proofer detects mRNA from HPV types 16, 18, 31, 33 and 45, whereas Gp5ϩ/6ϩ consensus PCR detects HPV DNA from the L1 region in Ͼ20 HPV types. We included all women with an index Pap smear diagnosis of ASCUS or LSIL (n ϭ 77). The index Pap smear refers to the smear taken together with the HPV testing. Information on Pap smears in the 10-year period before the inclusion in our study was obtained from CRN registers. Former abnormal smears mean any smear that is not normal or unsatisfactory and has been taken before the index smear in 2001. Follow-upSeventy-seven women were followed up for 24 months in the registers of the Cancer Registry of Norway (CRN) with subsequent Pap smears...

The coordinated screening programme provides a low cost way of increasing the coverage of the female population, and consequently has reduced the rate of invasive cervical cancer.

BackgroundCervical cancer incidence and mortality may be reduced by organized screening. Participant compliance with the attendance recommendations of the screening program is necessary to achieve this. Knowledge about the predictors of compliance is needed in order to enhance screening attendance.MethodsThe Norwegian Co-ordinated Cervical Cancer Screening Program (NCCSP) registers all cervix cytology diagnoses in Norway and individually reminds women who have no registered smear for the past three years to make an appointment for screening. In the present study, a questionnaire on lifestyle and health was administered to a random sample of Norwegian women. The response rate was 68%. To address the predictors of screening attendance for the 12,058 women aged 25-45 who were eligible for this study, individual questionnaire data was linked to the cytology registry of the NCCSP. We distinguished between non-attendees, opportunistic attendees and reminded attendees to screening for a period of four years. Predictors of non-attendance versus attendance and reminded versus opportunistic attendance were established by multivariate logistic regression.ResultsWomen who attended screening were more likely than non-attendees to report that they were aware of the recommended screening interval, a history of sexually transmitted infections and a history of hormonal contraceptive and condom use. Attendance was also positively associated with being married/cohabiting, being a non-smoker and giving birth. Women who attended after being reminded were more likely than opportunistic attendees to be aware of cervical cancer and the recommended screening interval, but less likely to report a history of sexually transmitted infections and hormonal contraceptive use. Moreover, the likelihood of reminded attendance increased with age. Educational level did not significantly affect the women's attendance status in the fully adjusted models.ConclusionsThe likelihood of attendance in an organized screening program was higher among women who were aware of cervical screening, which suggests a potential for a higher attendance rate through improving the public knowledge of screening. Further, the lower awareness among opportunistic than reminded attendees suggests that physicians may inform their patients better when smears are taken at the physician's initiative.

BACKGROUND: HPV16/18 detection may improve cervical cancer risk stratification and better guide which HPV-positive women warrant immediate colposcopy/biopsy. We estimated risks of cervical precancer and cancer by HPV genotype and cytology during the implementation phase of primary HPV testing in Norway. METHODS: A total of 3111 women, aged 34-69 years, testing HPV-positive at baseline and undergoing cytology testing from February 2015 to April 2018 had data available for analysis. Risk estimates with 95% confidence intervals (95%CIs) of cervical intraepithelial neoplasia grade 3 or more severe (CIN3+) were estimated for cytology results and HPV genotypes (HPV16, HPV18, and other high-risk HPV). RESULTS: CIN3+ risks were higher for HPV16/18 than other high-risk HPV genotypes. Among women with any cytologic abnormality [atypical squamous cells of undetermined significance or worse], immediate risks were 57.8% (95%CI = 53.0-62.6%) for HPV16, 40.2% (95%CI = 32.3-49.2%) for HPV18, and 31.4% (95%CI = 28.7-34.3%) for other high-risk HPV. Among those with normal cytology, CIN3+ risks were 19.9% (95%CI = 15.0-26.1%) for HPV16 positives, 10.8% (95%CI = 5.6-20.5%) for HPV18 positives, and 5.5% (95%CI = 4.2-7.1%) for other high-risk HPV. CONCLUSIONS: The benefits and harms of managing women based on HPV positivity and cytology results can be better balanced by inclusion of HPV genotyping in screening and choosing more conservative management for other high-risk HPV compared to HPV16/18.

Treatment with major excisional procedures, including LEEP, was associated with increased risks of preterm birth and spontaneous abortion. The risk of preterm birth was highest at early gestational ages and for those with the largest amount of tissue excised. Women should be informed about their future risk of adverse pregnancy outcomes, particularly preterm birth, after excisional treatment for cervical lesions.