Monica Lindell

Self-sampling of the vaginal fluid at home combined with high-risk HPV testing.

Background:Around 65% of women with cervical carcinoma in Sweden have not attended an organised screening. We therefore investigated the value of using self-sampling at home in combination with a test for high-risk human papilloma virus (HPV) to increase participation.Methods:A total of 2829 women 30–58 years old, who had not attended the organised screening for ⩾6 years, were recruited. They were offered self-sampling at home (Qvintip) and recommended to send the collected vaginal fluid to a laboratory for analysis of the presence of high-risk HPV (Hybrid Capture 2 method).Results:A total of 39.1% of the women accepted home sampling. These women disclosed a relatively high prevalence of high-risk HPV, which decreased with age, from 11.1% in women 30–39 years old to 2.9% in women ⩾50 years . Follow-up disclosed histological cervical intraepithelial neoplasm (CIN) 2–3 lesions in 43.2% of the women with a persistent HPV infection, corresponding to 2.0% of the total number of participating women. The sensitivity of a single smear to detect the histological CIN 2–3 lesions were only 52.6%, even if all abnormal smears (atypical squamous cells of unknown significance (ASCUS)–CIN 3)) were included.Conclusion:The use of self-sampling at home in combination with testing for high-risk HPV increases the participation rate of the organised screening and detects almost twice as many women with pre-malignant cell alterations (CIN 2–3) in comparison those with a single cytological smear.

Use of FTA card for dry collection, transportation and storage of cervical cell specimen to detect high-risk HPV.

BACKGROUND The FTA elute micro card, which enable the collection, transport, and archiving of DNA could be an attractive alternative to a liquid based collection system for detection of human papillomavirus (HPV). OBJECTIVES To develop a method based on the FTA elute micro card for dry collection of cervical epithelial cell samples, suitable for subsequent PCR-based HPV testing. STUDY DESIGN The method was evaluated by a comparison of the DNA collected by cytobrush and the regular FTA elute micro card from 50 cervical cell samples. The method was then used to estimate the DNA amount in 1040 samples applied to the indicating FTA elute micro card. RESULT The agreement in HPV positivity between the cytobrush and FTA samples (94%) was excellent (kappa=0.88, 95% CI 0.748-1). All the 1040 samples on the indicating FTA card had sufficient amounts of genomic DNA (>10 copies of a single copy gene) to be suitable for HPV typing. In 53 of the 1040 women the day in the menstrual cycle was noted, and the copy number during follicular phase day 9-13 was found to be statistically significantly lower than for the other three stages in the menstrual cycle (day 4-8, 14, >14) and during menopause. CONCLUSION The indicating FTA elute micro card represents a suitable medium for collection of cervical cell samples, although follow-up studies are needed to verify the detection of low frequency HPV types.

Self-sampling and HPV testing or ordinary Pap-smear in women not regularly attending screening: a randomised study

Background:Most women with cervical cancer have not participated in Pap-smear screening. Self-sampling of vaginal fluid in combination with high-risk HPV testing may be a method to increase the attendance rate.Methods:A total of 4060 women, 39–60 years old, who had not attended the organised Pap-smear screening for 6 years or more were randomised into two equal groups. A study group was offered to self-sample vaginal fluid (Qvintip) at home and/or recommended to attend the Pap-smear screening. The collected fluid after self-sampling was examined for the presence of high-risk HPV (Hybrid Capture 2 method). Controls were only recommended to attend the Pap-smear screening. The end point was a histological identification of CIN2–3.Results:The participation rate was 39% (771 out of 2000) in the self-sampling group and 9% (188 out of 2060) in the conventional cytology (P<0.001). The number of histological CIN2–3 alterations detected was 0.4% (8 out of 2000) among women offered self-sampling of vaginal fluid and 0.07% (3 out of 4060) in women offered Pap-smears. The odds ratio (OR) for offering self-sampling and HPV testing instead of Pap-smear screening for detection of CIN2–3 was OR=5.42 (95% CI: 1.30–31.8).Conclusion:Offering self-sampling of vaginal fluid followed by a high-risk HPV test was considerably more effective for detection of histological CIN2–3 lesions in comparison with offering Pap-test in a midwife reception in women not regularly attending organised screening.

Type-specific detection of high-risk human papillomavirus (HPV) in self-sampled cervicovaginal cells applied to FTA elute cartridge

BACKGROUND Most procedures for self-sampling of cervical cells are based on liquid-based media for transportation and storage. An alternative is to use a solid support, such as dry filter paper media. OBJECTIVES To evaluate if self-sampling of cervicovaginal fluid using a cytobrush (Viba-brush; Rovers Medical Devices B.V., Oss, The Netherlands) and a solid support such as the Whatman Indicating FTA Elute cartridge (GE Healthcare, United Kingdom) can be used for reliable typing of human papillomavirus (HPV), as compared to cervical samples obtained by a physician using a cytobrush and the indicating FTA Elute Micro card and biopsy analysis. STUDY DESIGN A total of 50 women with a previous high-risk (HR) HPV positive test were invited to perform self-sampling using the Viba-brush and the FTA cartridge and thereafter a physician obtained a cervical sample using the cytobrush and a FTA card, together with a cervical biopsy for histology and HPV typing. Detection of HR-HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 was performed using three multiplex real-time polymerase chain reaction (PCR) assays. RESULT All samples contained sufficient amounts of genomic DNA and the self-samples yielded on average 3.5 times more DNA than those obtained by the physician. All women that were positive for HR-HPV in the biopsy sample also typed positive both by self-sampling and physician-obtained sampling. For women with a histological diagnosis of cervical intraepithelial neoplasia grades 2-3 (CIN 2-3) all three HPV samples showed 100% concordance. A higher number of women were HPV positive by self-sampling than by physician-obtained sampling or by biopsy analysis. CONCLUSION The Viba-brush and the FTA cartridge are suitable for self-sampling of vaginal cells and subsequent HR-HPV typing.

Short-time repeat high-risk HPV testing by self-sampling for screening of cervical cancer

Background:Testing for high-risk human papillomavirus (HPV) in primary screening for cervical cancer is considered more sensitive, but less specific, in comparison with Pap-smear cytology. Women with persistent HPV infections have a higher risk of developing cervical intraepithelial neoplasia 2+ (CIN2+) lesions. This study was performed to evaluate the gain in specificity for detection of histologically confirmed CIN2+ lesions achieved by short-time repeat testing for high-risk HPV in women aged 30–65 years, with the primary sample for HPV analysis taken by self-sampling.Methods:A total of 8000 women in Uppsala County, aged 30–65 years, who had not attended organised screening for 6 years or longer, were offered self-sampling of vaginal fluid at home and the samples sent for HPV typing. Of these, 8% (669) were not possible to contact or had performed hysterectomy. Women positive for high-risk HPV in the self-sampling test were invited for a follow-up HPV test and a cervical biopsy on average 3 months after the initial HPV test.Results:In all, 39% (2850/7331) of invited women chose to perform self-sampling of vaginal fluid at home. High-risk HPV infection was found in 6.6% (188) of the women. In all, 89% of the women testing HPV positive performed a follow-up examination, on average 2.7 months, after the first test and 59% of these women were HPV positive in the follow-up test. The prevalence of CIN2+ lesions in women with an initial HPV-positive test was 23% (95% CI 18–30%) and in women with two consecutive HPV-positive tests was 41% (95% CI 31–51%). In women with two positive HPV tests, the prevalence of CIN2+ lesions varied from 49% in women at age 30–39 years to 24% in women at age 50–65 years. Short-time repeat HPV testing increased the specificity for detection of CIN2+ lesions from about 94.2% to 97.8%. The most prevalent HPV types were HPV16 (32%), followed by HPV18/45 (19%) and HPV 33/52/58 (19%).Conclusion:The short-time persistence of high-risk HPV infection in this age group was about 60%. Repeat testing for high-risk HPV using self-sampling of vaginal fluid can be used to increase the specificity in the screening for cervical cancer in women aged 30–65 years.

TP53 mutations predict for poor survival in de novo diffuse large B-cell lymphoma of germinal center subtype.

Presence of TP53 mutations has been associated with poor prognosis in diffuse large B-cell lymphoma (DLBCL), although this has remained controversial. The TP53 codon 72 polymorphism has shown negative impact on cancer survival, but this has not been analyzed in DLBCL. Furthermore, the MDM2 SNP309 has been associated with earlier age of onset in DLBCL. Here, we investigated the clinical impact of TP53 mutations, MDM2 SNP309 and TP53 codon 72 polymorphisms on survival in DLBCL of germinal center (GC) and non-GC subtypes. Thirteen of the 102 (12.7%) patients displayed TP53 mutations. Overall, TP53 mutations had a significant effect on lymphoma-specific survival (LSS, P=0.009) and progression-free survival (PFS, P=0.028). In particular, inferior survival was observed in TP53-mutated DLBCLs of GC subtype (LSS, P=0.002 and PFS, P=0.006). Neither MDM2 SNP309 nor the TP53 codon 72 polymorphism had an impact on age of onset or survival. Altogether, our data suggests that TP53 mutations are associated with poor outcome in GC-DLBCL patients.

Self-sampling of vaginal fluid and high-risk human papillomavirus testing in women aged 50 years or older not attending Papanicolaou smear screening.

Please cite this paper as: Lindell M, Sanner K, Wikström I, Wilander E. Self‐sampling of vaginal fluid and high‐risk human papillomavirus testing in women aged 50 years or older not attending Papanicolaou smear screening. BJOG 2012;119:245–248.

Human papilloma virus tests of normal cervical smears collected prior to the development of squamous carcinoma: a pilot study.

Human papilloma virus tests of normal cervical smears collected prior to the development of squamous carcinoma : a pilot study