Self-collected versus clinician-collected cervical samples for the detection of HPV infections by 14-type DNA and 7-type mRNA tests.

BACKGROUND: HPV self-sampling has been widely supported by the scientific community following a strong body of literature on the subject. Self-sampling is important in cervical cancer screening as it has been shown to improve participation. It is well documented that HPV-testing has proven superior to cytology with regards to sensitivity in detection of CIN and cancer. The value of self-collected samples is reliant on the quality of the molecular testing performed, as well as the patients' preference in sampling procedure and compliance to follow up on positive test results. Due to the incompatibility of self-samples and cytology, triage of HPV-DNA positives by testing for molecular biomarkers is highly warranted. METHODS: Our objective was to compare the detection rate of genital Human Papillomavirus (HPV) infection in self- and clinician-collected samples by a 14-type HPV-DNA test and a 7-type mRNA E6/E7 test. RESULTS: Five hundred five women were recruited. Each study participant had two sample collection procedures performed upon the same visit, alternating order in execution of the self-collection or the clinician-taken procedure first or second, 1010 samples in total. HPV-DNA prevalence was 22.8% in self-collected versus 19.2% in clinician-collected samples (P = 0.19). Overexpression of mRNA E6/E7 from 7 HPV types was 7.1 and 6.3%, respectively (P = 0.71). The difference between HPV-DNA and HPV-mRNA positivity rates were statistically significant in both self-collected (22.8% versus 7.1%, P < 0.001) and clinician-collected samples (19.2% versus 6.3%, P < 0.001). Overall agreement between the two collection methods was fair, with a concordance rate of 78.2% (390/505), k = 0.34 (95% CI: 0.25-0.44), P < 0.001, for the HPV-DNA test and 92.5% (467/505), k = 0.40 (95% CI, 0.25-0.56), P < 0.001, for the mRNA test, respectively. 96.8% of the participants reported they felt confident carrying out the self-collection themselves, and 88.8% reported no discomfort at all performing the procedure. CONCLUSIONS: This comparative study of two sampling methods reports fair agreement of HPV positivity rates between the self-collected and clinician-collected specimens using Abbott hrHPV and PreTect HPV-Proofer'7 tests. Only one third of HPV-DNA positive women had overexpression of mRNA E6/E7. TRIAL REGISTRATION: ISRCTN77337300 .

Using novel biomarkers to triage young adult women with minor cervical lesions: a cost-effectiveness analysis.

OBJECTIVE: To evaluate the short-term consequences and cost-effectiveness associated with the use of novel biomarkers to triage young adult women with minor cervical cytological lesions. DESIGN: Model-based economic evaluation using primary epidemiological data from Norway, supplemented with data from European and American clinical trials. SETTING: Organised cervical cancer screening in Norway. POPULATION: Women aged 25-33 years with minor cervical cytological lesions detected at their primary screening test. METHODS: We expanded an existing simulation model to compare 12 triage strategies involving alternative biomarkers (i.e. reflex human papillomavirus (HPV) DNA/mRNA testing, genotyping, and dual staining) with the current Norwegian triage guidelines. MAIN OUTCOME MEASURES: The number of high-grade precancers detected and resource use (e.g. monetary costs and colposcopy referrals) for a single screening round (3 years) for each triage strategy. Cost-efficiency, defined as the additional cost per additional precancer detected of each strategy compared with the next most costly strategy. RESULTS: Five strategies were identified as cost-efficient, and are projected to increase the precancer detection rate between 18 and 57%, compared with current guidelines; however, the strategies did not uniformly require additional resources. Strategies involving HPV mRNA testing required fewer resources, whereas HPV DNA-based strategies detected >50% more precancers, but were more costly and required twice as many colposcopy referrals compared with the current guidelines. CONCLUSION: Strategies involving biomarkers to triage younger women with minor cervical cytological lesions have the potential to detect additional precancers, yet the optimal strategy depends on the resources available as well as decision-makers' and women's acceptance of additional screening procedures. TWEETABLE ABSTRACT: Women with minor cervical lesions may be triaged more accurately and effectively using novel biomarkers.

HPV mRNA test in women with minor cervical lesions: experience of the University Hospital of North Norway.

In the Norwegian Cervical Cancer Screening Programme tests for detection of human papillomavirus (HPV) are used to triage women with minor cytological cervical lesions. The material in this study comprises samples from 1798 women in the period 2006-2008. The HPV test was performed according to the guidelines of the Norwegian Cancer Registry. The HPV mRNA test (PreTect HPV-Proofer) detects and types 5 high-risk genotypes (16, 18, 31, 33 and 45). The HPV mRNA results were compared to cytology and then biopsy up to December 2009. Women with minor cytological cervical lesions and negative HPV test were followed with a new PAP smear after 12 months. A total of 327 women (18%) were HPV mRNA positive. Of the 1798 women with minor cytological lesions, 232 women (13%) had moderate dysplasia, severe dysplasia or cancer and 144 women (8%) had severe dysplasia or cancer in biopsy. 57% of the women with a positive HPV mRNA test had moderate dysplasia, severe dysplasia or cancer. 37% had severe dysplasia or cancer. The sensitivity of the HPV mRNA test to detect moderate dysplasia, severe dysplasia or cancer was 81%. The specificity for moderate dysplasia, severe dysplasia or cancer was 91%. The negative predictive value (NPV) of the HPV mRNA test for moderate dysplasia, severe dysplasia or cancer was 97%. Of 11 women with cervical cancer, 10 were positive for HPV type 16 or 18. The HPV mRNA test seems more suitable than HPV DNA tests to triage women with minor cytological cervical lesions due to its higher specificity.

[Cancer patients' perception of the examination period prior to treatment]. / Kreftpasienters oppfatning av utredningstid før behandling.

From July 1990 to July 1991 252 cancer patients admitted consecutively to the Department of Oncology, University Hospital of Tromsø, were included in a questionnaire-based study. The aim of the study was to examine the delays involved in the diagnosis and treatment of cancer. The study also focused on the psychological distress related to these periods of delay. A significant correlation between psychological distress and the actual length of delay (weeks) was revealed (p < 0.01). psychological distress was also correlated positively to the degree of depression (p < 0.01). Women found delays more distressing than men (p < 0.01). Patients from the northern areas (Troms and Finnmark counties) considered a cancer unit in Northern Norway to be of greater importance than those living in the southern area (Nordland county).

Diagnostic delay causes more psychological distress in female than in male cancer patients.

From July 1990 to July 1991, 263 consecutive cancer patients admitted to our oncological unit for the first time were invited to participate in a questionnaire based study. 252 patients responded and were included in the final analysis. The aim of the survey was to examine the delays involved in diagnosis and treatment of cancer and the possible psychological distress associated to the different periods of delay. A shorter patient delay was found among patients under the age of 30 years (P < 0.005). Patients with higher education had a significantly shorter delay from the time of contact with the GP to admittance to the local hospital (P <0.005). The diagnostic delay was reported to be significantly more distressing for females compared to males (P <0.05). The reported psychological distress, however, correlated positively to the actual length of total delay (P<0.005) for both sexes. All patients reported that the delay between local hospital referral and admittance to the oncological unit to be the most distressing delay period to cope with.