In this task, you are given an abstract of article. Your task is to generate title for this article. Preferred titles are under thirty words.

BACKGROUND Human papillomavirus (HPV) testing is more sensitive for the detection of high-grade cervical lesions than is cytology, but detection of HPV by DNA screening in two screening rounds 5 years apart has not been assessed. The aim of this study was to assess whether HPV DNA testing in the first screen decreases detection of cervical intraepithelial neoplasia (CIN) grade 3 or worse, CIN grade 2 or worse, and cervical cancer in the second screening.
METHODS In this randomised trial, women aged 29-56 years participating in the cervical screening programme in the Netherlands were randomly assigned to receive HPV DNA (GP5+/6+-PCR method) and cytology co-testing or cytology testing alone, from January, 1999, to September, 2002. Randomisation (in a 1:1 ratio) was done with computer-generated random numbers after the cervical specimen had been taken. At the second screening 5 years later, HPV DNA and cytology co-testing was done in both groups; researchers were masked to the patient's assignment. The primary endpoint was the number of CIN grade 3 or worse detected. Analysis was done by intention to screen. The trial is now finished and is registered, number ISRCTN20781131.
FINDINGS 22,420 women were randomly assigned to the intervention group and 22 518 to the control group; 19 999 in the intervention group and 20,106 in the control group were eligible for analysis at the first screen. At the second screen, 19 579 women in the intervention group and 19,731 in the control group were eligible, of whom 16,750 and 16,743, respectively, attended the second screen. In the second round, CIN grade 3 or worse was less common in the intervention group than in the control group (88 of 19 579 in the intervention group vs 122 of 19,731 in the control group; relative risk 073, 95% CI 055-096; p=0023). Cervical cancer was also less common in the intervention group than in the control group (four of 19 579 in the intervention group vs 14 of 19,731; 029, 010-087; p=0031). In the baseline round, detection of CIN grade 3 or worse did not differ significantly between groups (171 of 19 999 vs 150 of 20,106; 115, 092-143; p=0239) but was significantly more common in women with normal cytology (34 of 19,286 vs 12 of 19,373; 285, 147-549; p=0001). Furthermore, significantly more cases of CIN grade 2 or worse were detected in the intervention group than in the control group (267 of 19 999 vs 215 of 20,106; 125, 105-150; p=0015). In the second screen, fewer HPV16-positive CIN grade 3 or worse were detected in the intervention group than in the control group (17 of 9481 vs 35 of 9354; 048, 027-085; p=0012); detection of non-HPV16-positive CIN grade 3 or worse did not differ between groups (25 of 9481 vs 25 of 9354; 099, 057-172; p=100). The cumulative detection of CIN grade 3 or worse and CIN grade 2 or worse did not differ significantly between study arms, neither for the whole study group (CIN grade 3 or worse: 259 of 19 999 vs 272 of 20,106; 096, 081-114, p=0631; CIN grade 2 or worse: 427 of 19 999 vs 399 of 20,106; 108, 094-124; p=0292), nor for subgroups of women invited for the first time (CIN grade 3 or worse in women aged 29-33 years: 102 of 3139 vs 105 of 3128; 097, 074-127; CIN grade 2 or worse in women aged 29-33 years: 153 of 3139 vs 151 of 3128; 101, 081-126; CIN grade 3 or worse in women aged 34-56 years: 157 of 16,860 vs 167 of 16 978; 095, 076-118; CIN grade 2 or worse in women aged 34-56 years: 274 of 16,860 vs 248 of 16 978; 111, 094-132).
INTERPRETATION Implementation of HPV DNA testing in cervical screening leads to earlier detection of clinically relevant CIN grade 2 or worse, which when adequately treated, improves protection against CIN grade 3 or worse and cervical cancer. Early detection of high-grade cervical legions caused by HPV16 was a major component of this benefit. Our results lend support to the use of HPV DNA testing for all women aged 29 years and older.
FUNDING Zorg Onderzoek Nederland (Netherlands Organisation for Health Research and Development).
Human papillomavirus testing for the detection of high-grade cervical intraepithelial neoplasia and cancer: final results of the POBASCAM randomised controlled trial.

Mesenchymal niche cells may drive tissue failure and malignant transformation in the hematopoietic system, but the underlying molecular mechanisms and relevance to human disease remain poorly defined. Here, we show that perturbation of mesenchymal cells in a mouse model of the pre-leukemic disorder Shwachman-Diamond syndrome (SDS) induces mitochondrial dysfunction, oxidative stress, and activation of DNA damage responses in hematopoietic stem and progenitor cells. Massive parallel RNA sequencing of highly purified mesenchymal cells in the SDS mouse model and a range of human pre-leukemic syndromes identified p53-S100A8/9-TLR inflammatory signaling as a common driving mechanism of genotoxic stress. Transcriptional activation of this signaling axis in the mesenchymal niche predicted leukemic evolution and progression-free survival in myelodysplastic syndrome (MDS), the principal leukemia predisposition syndrome. Collectively, our findings identify mesenchymal niche-induced genotoxic stress in heterotypic stem and progenitor cells through inflammatory signaling as a targetable determinant of disease outcome in human pre-leukemia.
Mesenchymal Inflammation Drives Genotoxic Stress in Hematopoietic Stem Cells and Predicts Disease Evolution in Human Pre-leukemia.

AIMS There is controversy in published studies regarding the role of repeat whole brain radiation (WBRT) for previously irradiated brain metastases. The aim of our retrospective study was to document the practice at Princess Margaret Hospital with respect to the re-irradiation of patients with progressive or recurrent brain metastatic disease after initial WBRT. MATERIALS AND METHODS A comprehensive computerised database was used to identify patients treated for brain metastases with more than one course of WBRT between 1997 and 2003. Seventy-two patients were treated with WBRT for brain metastases and retreated with WBRT at a later date. The records of these patients were reviewed.
RESULTS The median age was 56.5 years. The most common primary sites were lung (51 patients) and breast (17 patients). The most frequent dose used for the initial radiotherapy was 20 Gy/5 fractions (62 patients). The most common doses of re-irradiation were 25 Gy/10 fractions (22 patients), 20 Gy/10 fractions (12 patients), 15 Gy/5 fractions (11 patients) and 20 Gy/8 fractions (10 patients). Thirty-one per cent of patients experienced a partial clinical response after re-irradiation, as judged by follow-up clinical notes; 27% remained stable; 32% deteriorated after re-irradiation. Patients who had Eastern Cooperative Oncology Group performance status 0-1 at the time of retreatment lived longer. In responders, the mean duration of response was 5.1 months. The median survival after re-irradiation was 4.1 months. One patient was reported as having memory impairment and pituitary insufficiency after 5 months of progression-free survival.
CONCLUSION Repeat radiotherapy may be a useful treatment in carefully selected patients. With increased survival and better systemic options for patients with metastatic disease, more patients may be candidates for consideration of repeat WBRT for recurrent brain metastases, but prospective studies are needed to more clearly document their outcomes.
Value of whole brain re-irradiation for brain metastases--single centre experience.