LRCTC News - Home

New technique detects cancer cells with sound
11 May 2012

Using lasers and sound, the researchers are able to create much higher-quality images of body parts.

A new imaging technology called photo-acoustic tomography is being developed by researchers at Washington University in St. Louis, Reuters reports in a video. Using lasers and sound, the researchers are able to create much higher-quality images of body parts than they currently can.

"It's actually a way of using sound to detect optical features," researcher Lihong Wong tells Reuters. "Instead of looking at optical structures, we're listening to optical structures. Light is beamed at the body and absorbed by the tissues. It then scatters, and causes a rapid increase in temperature, which then produces sound waves, Reuters reports. Researchers then detect these sound waves, and create an optical image of the tissues and organs. Wong adds that this technology will give doctors a detailed look at what's happening in the body in real time. The hope, Reuters adds, is that they can use this method to detect early signs of cancer before it develops into a tumor, especially in tissues and organs that aren't easily imaged by conventional means.

Scientific American May 5,2012  New technique detects cancer cells with sound

Global burden of cancers attributable to infections in 2008: a review and synthetic analysis
11 May 2012

Infections with certain viruses, bacteria, and parasites have been identified as strong risk factors for specific cancers.

Invaders from Another Cell Line
27 April 2012

Retractions of scientific papers are usually awkward, and sometimes involve investigations, firings, or scandal

In the case of Robert Mandic, a researcher at the University Hospital Giessen and Marburg in Germany, the retraction of an article he wrote for Oral Oncology didn't involve fraud or malfeasance, but "it wasn't pleasant," he tells The Wall Street Journal's Amy Dockser Marcus. Mandic's experiments and subsequent paper had been about head and neck cancer, but after the work was published, he realized that the cell lines he'd worked with had actually been cervical cancer lines. "Dr. Mandic entered a largely secret fellowship of scientists whose work has been undermined by the contamination and misidentification of cancer cell lines used in research labs around the world," Marcus writes. "Cancer experts seeking to solve the problem have found that a fifth to a third or more of cancer cell lines tested were mistakenly identified — with researchers unwittingly studying the wrong cancers, slowing progress toward new treatments and wasting precious time and money."

There have been hundreds such documented cases caused either by mislabeling, carelessness, or other mistakes, she adds. One of the biggest problems is also one of the most famous — aggressive cervical cancer cells taken from Henrietta Lacks in 1951, and used for decades in labs all over the country, have been known to take over other cancer cell lines, sometimes without researchers knowing, Marcus says. Further, cell lines repositories in the US, UK, Japan, and Germany have estimated that anywhere between 18 percent and 36 percent of cancer cell lines are mislabeled.

"The National Institutes of Health have, so far, not required cell line authentication as a condition of receiving federal grants," Marcus says. "One challenge is getting scientists to acknowledge their cell line is contaminated. The prevailing attitude, according to researchers, is that the other lab's cell line may be contaminated but not mine

Oral Oncology ; Robert Mandic,  University Hospital Giessen and Marburg, Germany

The Wall Street Journal; Amy Dockser Marcus.  23rd April 2012

 

Target set on cancer gene MCL1
20 April 2012

A research team pursuing one of the most commonly altered genes in cancer has laid a critical foundation for understanding this gene that could point the way toward developing drugs against it.

The study highlights several compounds that repress MCL1. In addition, the Broad says, the study reports a companion gene, BCL-xL, that can help predict whether a specific tumor is dependent on MCL1 for its survival. "It was not immediately obvious that MCL1 was such an attractive therapeutic target in cancer," says the Broad's Todd Golub. "But once it became clear that MCL1 was something that we wanted to turn off in tumor cells, we faced two additional problems: we didn't know which tumors depend on it for survival and there wasn't an obvious path to drug discovery. This paper addresses those two challenges."

The researchers started by suppressing MCL1 in several cancer cell lines to determine which ones were dependent on the gene. They then looked for a marker that could predict which cell lines were dependent, and found that BCL-xL was the clearest indicator, the Broad says. The team also tested about 3,000 compounds to search for ones that turned off MLC1 in cancer cells, and found some that could serve as a starting point towards developing a drug specifically to target MCL1.

Cancer Cell - April 2012

Todd Golub, director of the Broad’s Cancer Program 

Charles A. Dana Investigator in Human Cancer Genetics at the Dana-Farber Cancer Institute.

High Throughput for HPV
05 April 2012

Sensitive and specific detection of human papillomaviruses (HPV) in cervical samples is a useful tool for the early diagnosis of epithelial neoplasia and anogenital lesions.

 

Recent studies support the feasibility of HPV DNA testing instead of cytology (Pap smear) as a primary test in population screening for cervical cancer. This is likely to be an option in the near future in many countries, and it would increase the efficiency of screening for cervical abnormalities. We present here a microarray test for the detection and typing of 15 most important high-risk HPV types and two low risk types. The method is based on type specific multiplex PCR amplification of the L1 viral genomic region followed by ligation detection reaction where two specific ssDNA probes, one containing a fluorescent label and the other a flanking ZipCode sequence, are joined by enzymatic ligation in the presence of the correct HPV PCR product. Human beta-globin is amplified in the same reaction to control for sample quality and adequacy. The genotyping capacity of our approach was evaluated against Linear Array test using cervical samples collected in transport medium. Altogether 14 out of 15 valid samples (93%) gave concordant results between our test and Linear Array. One sample was HPV56 positive in our test and high-risk positive in Hybrid Capture 2 but remained negative in Linear Array. The preliminary results suggest that our test has accurate multiple HPV genotyping capability with the additional advantages of generic detection format, and potential for high-throughput screening.

Jarmo Ritari et al   Institute of Biotechnology, University of Helsinki, Helsinki, Finland, PLoS One 30 March 2012

 

p16INK4a and p14ARF mRNA expression in Pap smears is age-related
02 April 2012

In Modern Pathology, researchers from Charité-Universitätsmedizin in Berlin report that expression of p16INK4a and p14ARF mRNA in Pap smears is related to age

Expression of high-risk HPV oncogenes results in a strong overexpression of cellular protein p16^INK4a. Immunohistochemical staining for p16^INK4a is widely used as diagnostic marker. However, p16^INK4a upregulation was also described as a biomarker of age. Here we analyzed p16^INK4a expression in cervical smears to investigate if patient age may influence p16^INK4a-based cervical cancer diagnosis. p14^ARF was analyzed as a related supportive biomarker. Cervical scrapes were taken and stored in RNAlater. Total RNA was extracted, and cDNA was analyzed for expression of p16^INK4a and p14^ARF relative to β-actin, by real-time reverse transcriptase PCR SYBR-Green I assays. Patient-derived smears referred as HSIL (n=45) had 6.27-fold higher p16^INK4a mRNA expression than smears of cytologically normal and HPV-negative persons (n=48). Expression of p14^ARF was 4.87-fold higher. When women with normal diagnoses were stratified for age, a significantly enhanced p16^INK4a (2.88-fold) and p14^ARF (1.9-fold) expression was observed as a consequence of ageing. A significant age-dependent upregulation was also observed in older HSIL patients (2.54-fold). Our study revealed significantly enhanced expression of p16^INK4a/p14^ARF mRNA in cervical scrapes referred to as HSIL compared with normal women. An age-dependent bias has to be considered when quantifying these tumor suppressor genes, with respect to cervical cancer development.

Authors:

 

 

 

 

 

 

 

 

 

Helmut von Keyserling, Wolfgang Kühn, Achim Schneider, Thomas Bergmann and Andreas M Kaufmann

 

Modern Pathology 25, 465-470 (March 2012) | doi:10.1038/modpathol.2011.179

Viruses Recruited as Killers of Tumors
02 April 2012

Viruses can be designed to attack tumors.

In 1951, a 4-year-old boy with leukemia contracted chickenpox. His liver and spleen, swollen by the cancer, soon returned to normal, and his elevated blood cell count fell to that of a healthy child.

His doctors at the Laboratory of Experimental Oncology in San Francisco were thrilled by his sudden remission, but the blessing was short-lived. After one month, his leukemia returned and progressed rapidly until the child’s death.

In the early 1900s, not much could be done for cancer patients. Unless surgeons could excise a tumor, the disease typically spelled a swift and inevitable end. But in dozens of published cases over the years, doctors noticed a peculiar trend: Struggling cancer patients sometimes enjoyed a brief reprieve from their malignancies when they caught a viral infection.

It was not a coincidence. Common viruses sometimes attack tumor cells, researchers discovered. For decades, they tried to harness this phenomenon, to transform it into a cancer treatment. Now, after a long string of failures, they are nearing success with viruses engineered to kill cancer.

“It’s a very exciting time,” said Dr. Robert Martuza, chief neurosurgeon at the Massachusetts General Hospital and professor of neuroscience at Harvard Medical School. “I think it will work out in some tumor, with some virus.” Candidates are already in advanced trials, he noted.

Cancer cells are able to replicate wildly, but there’s a trade-off: They cannot ward off infection as effectively as healthy cells. So scientists have been looking for ways to create viruses that are too weak to damage healthy cells yet strong enough to invade and destroy tumor cells. It has been a long, difficult challenge.

Researchers started down this road in 1904, when they discovered that women with cervical cancer temporarily recovered when given a rabies vaccination. By midcentury, physicians were administering live viruses to cancer patients. They tried infecting terminally ill children with polio and adenovirus. They injected patients with concoctions from the feces of normal children, from sick chickens, and from “feline spleen suspension” of rural kittens infected with “cat plague.”

These experiments proved ill fated. The cancer returned, or — in the worst cases — the injections themselves caused “the development of lethal infection in the host,” according to a 1964 American Journal of Pathology report.

The field was abandoned for a time. But in 1991, Dr. Martuza seized upon the idea of using the herpes simplex virus (HSV-1) as a cancer-fighter.

The genome of HSV-1 is comparatively large and can accommodate a number of mutations and deletions. Dr. Martuza weakened the virus by removing some of its genes. The modified virus was injected into mice with brain cancer, and it did bring about remission. But most of the mice died of encephalitis.

In 1990, Bernard Roizman, a virologist at the University of Chicago, found a “master gene” in the herpes virus. When this gene is removed, the virus no longer has the strength to overcome healthy cells’ defenses. As it turned out, the modified virus was so crippled that it could only slow tumor growth.

Then, in 1996, Dr. Ian Mohr, a virologist at New York University, stumbled on a way of further altering Dr. Roizman’s crippled virus. He exposed it repeatedly to cancer cells until a new viral mutant evolved with the ability to replicate in those cells.

Dr. Mohr and a doctoral student, Matt Mulvey, then engineered a way for their virus to evade the immune system, making it an even more potent cancer-killing agent.

Unlike chemotherapy, which can diminish in effectiveness over time, oncolytic viruses multiply in the body and gain strength as the infection becomes established. In addition to attacking cancer cells directly, some also produce an immune response that targets tumors.

Today, several potential cancer-fighting viruses are in trials, including two in Phase 3 trials.

An engineered form of vaccinia — the viral agent that helped eradicate smallpox — is being tested against advanced liver cancer, the third leading cause of cancer deaths globally. In a recent trial, survival for patients treated with high doses of the virus, called JX-594, doubled to 14 months from 7, compared with that of patients treated with low doses.

“To see that kind of response in a randomized trial is simply unheard of,” said Tony Reid, the director of clinical investigation at the Moores Cancer Center of the University of California, San Diego, who has no financial ties to the virus’s manufacturer.

A herpes virus based on Dr. Mohr’s original discovery is in advanced trials against melanoma; initial data showed a 26 percent response rate in patient regression and survival. A reovirus is being tested against head and neck cancers, often difficult to treat.

According to the researchers, the side effects of treatment with these viruses are minimal, and include nausea, fatigue and aches. “In comparison to what happens with standard chemotherapy, flulike symptoms are very manageable,” said Dr. Reid, who has treated hundreds of patients with oncolytic viruses.

Oncolytic viruses are likely to find a place in medicine, especially paired with other therapies targeting difficult and aggressive tumors, said Gary Hayward, a virologist at the Johns Hopkins Herpesvirus Research Program. But the “biology is complex,” Dr. Hayward warned, and progress is likely to be incremental.

Dr. Mulvey now heads a firm in Baltimore testing viruses to fight melanoma and bladder cancer. The biggest challenge now, he said, is simply convincing others that the new treatment is “not science fiction.”

New York Times - 

Published: March 19, 2012

By RACHEL NUWER

Pan-London HPV Implementation Meeting
09 March 2012

The first pan-london HPV Implementation meeting was held on Firday 9th March at Northwick Park Hospital.

The presentation is now available to view through the following link.

Screening and cervical cancer cure: population based cohort study
09 March 2012

Objective To determine whether detection of invasive cervical cancer by screening results in better prognosis or merely increases the lead time until death.

Participants All 1230 women with cervical cancer diagnosed during 1999-2001 in Sweden prospectively followed up for an average of 8.5 years.

Main outcome measures Cure proportions and five year relative survival ratios, stratified by screening history, mode of detection, age, histopathological type, and FIGO (International Federation of Gynecology and Obstetrics) stage.

Results In the screening ages, the cure proportion for women with screen detected invasive cancer was 92% (95% confidence interval 75% to 98%) and for symptomatic women was 66% (62% to 70%), a statistically significant difference in cure of 26% (16% to 36%). Among symptomatic women, the cure proportion was significantly higher for those who had been screened according to recommendations (interval cancers) than among those overdue for screening: difference in cure 14% (95% confidence interval 6% to 23%). Cure proportions were similar for all histopathological types except small cell carcinomas and were closely related to FIGO stage. A significantly higher cure proportion for screen detected cancers remained after adjustment for stage at diagnosis (difference 15%, 7% to 22%).

Conclusions Screening is associated with improved cure of cervical cancer. Confounding cannot be ruled out, but the effect was not attributable to lead time bias and was larger than what is reflected by down-staging. Evaluations of screening programmes should consider the assessment of cure proportions

BMJ 2012; 344 doi: 10.1136/bmj.e900 (Published 1 March 2012)

 

A. Castanon, S. Ferryman, J. Patnick and P. Sasieni Review of cytology and histopathology as part of the NHS Cervical Screening Programme audit of invasive cervical cancers
18 January 2012

To audit pathology slide reporting in the Cervical Screening Programme in England by reviewing cytology and histology slides from women subsequently diagnosed with invasive cervical cancer.

Cytopathology;

Article first published online: 16 JAN 2012

DOI: 10.1111/j.1365-2303.2011.00948.x

© 2012 Blackwell Publishing Ltd

R. M. Austin and C. Zhao Type 1 and type 2 cervical carcinomas: some cervical cancers are more difficult to prevent with screening
18 January 2012

Although the Papanicolaou (Pap) smear is medical history’s most successful cancer screening test, some cervical cancers are more difficult to prevent with screening than others.

Although the Papanicolaou (Pap) smear is medical history’s most successful cancer screening test, some cervical cancers are more difficult to prevent with screening than others. Cervical cancers that are difficult to prevent are seen disproportionately among interval cancers arising in previously screened women and in Pap test litigation. These include (i) rapidly progressing cervical cancers; (ii) cervical cancers in younger women; (iii) glandular cervical cancers; and (iv) cervical cancers in elderly women. Screening protocols have generally been designed to optimize prevention of slower-growing cervical squamous carcinomas in middle-aged women. To focus further attention on the heterogeneous screening challenges posed by different cervical cancers, we designate the more screening preventable majority as type 1 cervical cancers and the more difficult to prevent minority as type 2 cervical cancers. We review available data on why some cervical cancers are more difficult to prevent with screening and newer methods that may improve prevention.

Cytopathology;

Article first published online: 16 JAN 2012

DOI: 10.1111/j.1365-2303.2011.00955.x

© 2012 Blackwell Publishing Ltd

Multinucleation of koilocytes is in fact multilobation and is related to aberration of the G2 checkpoint
10 January 2012

To clarify the fine structure of koilocytes and correlate this with genetic aberration of the G2 checkpoint.

 

Method;

Three dimensial reconstruction from confocal fluorescent images,together with functional assays for key molecules of the G2 checkpoint-cdc2 and cyclin B1 was performed in human uterine cervical samples.After confirming  22 HPV types using a DNA chip from 30 cervical swabs,previously confirmed as 15 cervical low grade and 15 high grade intraepithelial lesions,the activity of molecules involved in the G2 checkpoint was evaluated using Western blotting for cyclin B1,cdc2 and phospho-cdc2(Y15 and T161), a nuclear extraction fractional assay,and a reverse transciption polymerase chain reaction assay.In addition,three dimensional confocal image restoration was performed on confirmed  CIN tissue samples.

Result: T161 phospho-cdc2 and cyclin B1 expression was higher in HPV infected cervical lesions than in normal samples.Immunofluorescence ,revealed that cyclin B1 was present predominantly in the nuclei of HPV infected cells,confirming the results of the nuclear fractional assay.On restoration of three dimensional confocal images ,the multinucleation of koilocytes was revealed to be multilobation of a single nucleus,rather than true multinucleation.This multilobation apeared to be associated with chromosomal instability and aberration of the G2 checkpoint.

Conclusion: The multiple nuclei of koilocytes are in fact multilobation of a single nucleus, and this phenomenon is associated with upregulation of gene products related to the G2 checkpoint

N.H. Cho et al J Clin Pathol 2005;58: 578-582 

Borderline nuclear change, high-grade dyskaryosis not excluded: current concepts and impact on clinical practice
09 December 2011

The purpose of this study was to determine the validity and accuracy of using B/HG to identify potential cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+).

Borderline nuclear change, high-grade dyskaryosis not excluded: current concepts and impact on clinical practice Objective: Borderline nuclear change, high-grade dyskaryosis not excluded (B/HG) is a subcategory of the borderline category recommended by the British Society for Clinical Cytology as warranting direct referral to colposcopy. This subcategory is equivalent to the Bethesda category of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H). The purpose of this study was to determine the validity and accuracy of using B/HG to identify potential cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+). Methods: Data were collected from the hospital pathology database for borderline, B/HG and high-grade cytology (moderate dyskaryosis and above), and their respective histological and colposcopic outcomes. SPSS was used for data analysis. Results: Of the 84 799 total cytology samples screened between July 2006 and December 2009, 5225 (6.1%) were reported as borderline, 309 (0.4%) as B/HG and 1222 (1.4%) as high-grade cytology. Thus, B/HG comprised 5.9% of the overall borderline category, in keeping with national guidelines (<10%). CIN2+ was confirmed in 86.6% of high-grade, 40.8% of B/HG and 3.0% of borderline cytology. Of 309 women reported with B/HG cytology, 239 had colposcopy. Colposcopic appearances showed a positive predictive value (PPV) of 71.8% for detecting CIN2+ and a negative predictive value of 60.7%. Conclusions: The B/HG category was associated with a significantly higher incidence of CIN2+ compared with borderline cytology as a whole. This refining performance justifies its existence. Colposcopic appearances had a high PPV for detecting CIN2+. Therefore, colposcopy is recommended in patients with B/HG cytology and treatment should be offered if high-grade colposcopic changes are seen.

Article first published online: 4 DEC 2011

DOI: 10.1111/j.1365-2303.2011.00943.x

© 2011 Blackwell Publishing Ltd

S. S. Hoo, A. Patel, H. Buist, K. Galaal, J. D. Hemming and R. Naik
Cytopathology

Making Sense of the New Cervical-Cancer Screening Guidelines
02 December 2011

This week in NEJM, Brigham and Women's Hospital's Sarah Feldman offers her interpretation of the new cervical cancer screening guidelines

Sarah Feldman, M.D., M.P.H.

November 23, 2011 (10.1056/NEJMp1112532)

DH announces switch to Gardasil for HPV vaccination programme
28 November 2011

The vaccine used for the HPV immunisation programme will be replaced from the beginning of the next school year.

Gardasil will replace Cervarix as the HPV vaccine used routinely in the programme to prevent cervical cancer in girls aged 12 to 13 from next year.

Both Gardasil and Cervarix protect against the two types of HPV virus that cause more than 70% of cervical cancer in England, but only Gardasil protects against two types of HPV virus that cause 90% of genital warts.

In 2008, NHS recommended the use of the Cervarix vaccine when the HPV immunisation programme was rolled out, controversially going against recommendations from the BMA and the Joint Committee on Vaccination and Immunisation that the Government used Gardasil.

Professor David Salisbury, the Government's director of immunisation, said: ‘We have one of the best HPV vaccination programmes in the world and we want that success to continue. It will be tremendous to see rates of cervical cancer falling. The number of women getting abnormal results from HPV screening will also fall. Many women will no longer have to live through the worry and stress of follow-up after screening, including treatment for precancerous lesions.'

He added: ‘It's not unusual for the NHS to change vaccines or other medicines – it can happen following competitive tendering exercises or when new research findings come to light.'

In 2010, research showed that Gardasil prevents 95.7% of HPV-type-related infections, cervical pre-cancers, genital lesions and genital warts, according to results from a four-year follow-up study of 4,000 women. Another study in September this year found that Cervarix would have to be £19 to £35 cheaper per dose to be as cost-effective as Gardasil, mainly due to a lack of protection against genital warts.

Sexual health specialists argue that it costs £23m to treat the 100,000 cases of genital warts that occur in the UK every year, and that preventing them at the same time would be cost effective.

An Australian study in 2008 showed that, after the country started vaccinating with Gardasil in 2007, the number of cases of genital warts in young women attending a large sexual health centre fell by 25%.

Since 2008 the HPV vaccine has been offered routinely in the UK to girls aged 12 to 13, with catch up programmes available for girls up to 18. Since then, 1.5 million young women and girls have been protected.

Dr Colm O'Mahony, consultant in genitourinary medicine at Countess of Chester Hospital and a member of the British Association for Sexual Health and HIV, said: ‘I wrote for years to Alan Johnson and Dawn Primarolo pleading with them to choose Gardasil instead of Cervarix, but to no avail. Finally common sense has prevailed and we now will have the same benefit given to our young men and women that almost all other developing countries have already achieved'.

GlaxoSmithKline, the producer of Cervarix, told Pulse they chose not to compete in the tendering process for the HPV vaccination programme. A spokesman for GSK said the company ‘will not participate in tenders where the specifications mean that it cannot effectively compete without undermining the value of our vaccines'

PULSE - Monday 28th November 2011 Author James Brown

Human papillomavirus testing in primary cervical screening and the cut-off level for hybrid capture 2 tests: systematic review
23 November 2011

Objective To determine the trade-off between the sensitivity and the specificity for high grade cervical intraepithelial neoplasia at hybrid capture 2 cut-off values above the standard ?1 relative light units/cut-off level (rlu/co).

Design Systematic review.

Data sources PubMed.

Study selection Randomised controlled trials in primary cervical screening using hybrid capture 2 testing in the intervention arms. Articles published until August 2010 were included if the numbers of women with positive test results and with cervical intraepithelial neoplasia were stratified by hybrid capture 2 cut-off levels.

Participants Women in the baseline screening rounds of the trials.

Interventions Hybrid capture 2 screening in the baseline round including the diagnostic follow-up as practised in the randomised controlled trials and as reported by hybrid capture 2 cut-off values.

Results Owing to heterogeneity in the trials, meta-analysis was not possible. Including cut-off values up to ≥10 rlu/co, 25 observation points were available for analysis. The relative sensitivity for cervical intraepithelial neoplasia grade III or higher at cut-off levels of ≥2, ≥4 or ≥5, and ≥10 rlu/co compared with a cut-off level of ≥1 rlu/co varied by trial, but at their lowest they were 0.97, 0.92, and 0.91, respectively. A similar pattern was observed for cervical intraepithelial neoplasia grade II or higher. The specificity would increase by at least 1%, 2%, and 3%, respectively, so that up to 24%, 39%, and 53%, of positive hybrid capture 2 test results not associated with high grade neoplasia could be avoided. Only two outliers existed to this general pattern.

Conclusions Although the data were derived from the baseline screening rounds only, the decrease in the sensitivity for high grade cervical intraepithelial neoplasia using a hybrid capture 2 cut-off level between ≥2 rlu/co and ≥10 rlu/co seemed acceptable given the international recommendations for testing for human papillomavirus DNA in cervical screening, which require 90% or more sensitivity for cervical intraepithelial neoplasia grade II or higher compared with hybrid capture 2 at ≥1 rlu/co. The data suggest that the hybrid capture 2 cut-off level could be increased in primary screening; this seems reasonably safe and is significantly less burdensome for women.

1. Matejka Rebolj, postdoctoral researcher1,
2. Jesper Bonde, senior researcher23,
3. Sisse Helle Njor, postdoctoral researcher1,
4. Elsebeth Lynge, professor of epidemiology1

BMJ 2011  342 doi: 10.1136/bmj.d2757 (Published 23 rd May 2011)

 

Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial
23 November 2011

We report vaccine efficacy against CIN3+ and adenocarcinoma in situ (AIS) in the end-of-study analysis of PATRICIA (PApilloma TRIal against Cancer In young Adults).

Self-collection of vaginal specimens for human papillomavirus testing in cervical cancer prevention (MARCH): a community-based randomised controlled trial
23 November 2011

Vaginal self-sampling for human papillomavirus (HPV) DNA testing could increase rates of screening participation.

Incidence of cervical intraepithelial neoplasia grade 2 or worse in colposcopy-negative/human papillomavirus-positive women with low-grade cytological abnormalities
23 November 2011

To determine the risk of incident high-grade cervical intraepithelial neoplasia (CIN) in human papillomavirus (HPV) -positive women with low-grade cytological abnormalities who had a satisfactory normal colposcopy.

Cervical cancer diagnosis rate rises among women in their 20s
07 November 2011

The next step is to encourage more girls aged 12 and 13 to be vaccinated againt the virus that triggers the disease, say experts

HPV Cervical Cancer Test Inconclusive for Women Over 30, Panel Says
28 October 2011

A U.S. advisory panel declined to endorse human papillomavirus screening to detect cervical cancer in women old than 30, saying the tests yield inconclusive results.

Less than a month after it issued a warning on the usefulness of PSA screening for prostate cancer, a US government advisory panel says HPV screening may not be very accurate for detecting cervical cancer in women older than 30, reports Bloomberg's Adriel Bettelheim. A draft report from the US Preventive Services Task Force says more evidence is needed to declare HPV screening — usually done by a gynecologist as a test of the cells near the cervix for evidence of the virus — a useful tool for this particular age group,

A Combination of 'Omics
18 October 2011

As?promising?as proteomics research is in the search for cancer biomarkers, sometimes?looking for lone proteins is not enough

Clinical Proteomic Tumor Analysis Consortium, or CPTAC, a consortium of five different centers, each of which maintains its own, separate collaborative project.The collaborators from the five centers got together to discuss their strategy. It was decided, Ellis says, that the project would proceed in two phases — discovery and verification.
In addition, the five centers have agreed to split their work into two arms — a clinical and a cancer biology arm. "The hypothesis [of the clinical arm] is that the genome-driven tumor secretome is a source of plasma biomarkers of clinical utility. And what all that means is that we will map protein expression in the context of genomic aberration, in the context of breast and ovarian cancer TCGA samples," Ellis says. "Of course we'll also explore indirect hypotheses that go something like, 'Tumor suppressor X is deleted, leading to deregulated mRNA Y, which encodes a secreted protein Z, which can also be detected in the plasma genome.' So basically the concept is to combine bioinformatics and gene function studies in the context of the TCGA data to come up with a list of candidates which can be searched for." This is quite different from the traditional cancer proteomics approach, which largely involves doing untargeted mass spectrometry on samples from cancer cases and controls in the hope of finding protein biomarkers. "Proteomics works much better if you know what you're looking for because you can instruct the machine to look for certain peptide sequences," Ellis adds.

The Breakdown

Participants: Matthew Ellis and Reid Townsend, Washington University in St. Louis; Morgan Giddings, Boise State University; Xian Chen, University of North Carolina, Chapel Hill
Funding: The Cancer Proteomic Center at Washington University, University of North Carolina, and Boise State University is slated to receive around $2.2 million in 2011, and a total of about $10 million for the project's five-year run.
Timeline: The CPTAC project as a whole has a set timeline of five years, with an external review at the three-year mark to determine whether it will continue the following two years.

Source: GenomeTechnology  October 2011 By Christie Rizk

www.genomeweb.com

Impending death of scientific journals ?
17 October 2011

Benchfly's Alan Marnett says, "now that the 21st century is here, it's time to start thinking about the "impending death of scientific journals" and just what kind of "fast-paced, technologically savvy" system might suitably replace them

For centuries, researchers have relied on journal publishers to inform the community about their discoveries.Since a researcher's publication record can affect decisions about hiring, compensation, and funding, it's an important aspect of a scientific career. But some scientists have said that journal impact factors aren't accurate representations of a paper's significance. So Marnett says the idea would be not to obliterate the scientific journal itself, but to change the way it is constructed and presented, using modern technologies. Rather than being published on paper, he suggests labs could begin publicizing their papers on their Web sites. Peer review would remain an important part of the process, Marnett adds, but rather than research being reviewed by two or three appointed people, feedback could come from a large online community. "Actions such as rating articles, leaving comments, tracking downloads, counting bookmarks, and quantifying social sharing are all valid, real-time metrics of user response to content," Marnett says. He also suggests that funds no longer used to cover publication costs could be spent instead on essentials for the lab. "The Internet has changed almost every facet of our lives so when it comes to our own profession we shouldn’t be too quick to assume evolution won’t apply to us too," Marnett says.

In a Benchfly poll, 36 percent of respondents indicated that they think journals will no longer be the primary mode for scientific publication in the next 20 years. Thirty-one percent of respondents said the same would happen within a decade.

 

Cervical cancer test likely to 'overwhelm' diagnostic services
30 September 2011

Colposcopy services are set to be inundated with GP referrals as a result of HPV testing being added to the NHS cervical cancer screening programme, with a Department of Health GP adviser predicting a 60% spike in demand.

Dr Jane Woyka, a member of the newly formed DH HPV Pilot Implementation Group and a GP in Harrow, west London, told Pulse adding the test would reduce GP workload but could lead to backlogs in processing patients with the diagnostic service likely to be ‘overwhelmed'.

It comes as the first evaluation of pilots where HPV testing was added to cervical screening - published in the British Journal of Cancer - found the number of women going for further unnecessary tests was cut by a third.

The study by the Institute of Cancer Research looked at more than 10,000 women aged 25-64 who were part of the NHS Cervical Screening Programme and whose first smear test had shown mild or borderline abnormalities in the cervix. These cervical screening samples were then tested for HPV, with 3,581 women (35%) found to be HPV negative and returned to routine screening.

Professor Julietta Patnick, director of the NHS Cancer Screening Programme, said she was ‘very pleased' with the results of the pilots.

‘By incorporating HPV testing into our current screening programme in this way,we will be able to significantly reduce the number of repeat cytology tests required and to target our colposcopy services more effectively,' she said.

The inclusion of HPV testing in the cervical cancer screening programme was due to be expanded beyond the six pilot sites in April, although Pulse revealed in May that the rollout had been hit by delays and the programme now hopes it was be completed ‘within the next year'.

Dr Woyka, who spent ten years on the DH Advisory Committee on Cervical Screening, warned that the extra demand for diagnostics would stretch colposcopy services to the limit.

‘There will increased workload to start with as the colposcopy service will get more referrals because the borderline cases will be sent to them directly so that will be a big challenge. There will be big issues for the service that could be overwhelmed as there will be an increase of at least 60%, which is huge.'

But GP workload would be cut, she added: ‘This will impact a lot on our management of borderline results.The amount of work and the amount of patient anxiety will be significantly reduced.'

What is changing?

How it works currently

Women with a borderline test result are recalled every six months, up to three times, and on the third occasion are sent for a colposcopy

Under the new system

Borderline test results prompt an HPV test and if positive, patients are referred directly to coploscopy. If negative the patient returns to a normall cal and recall.

Published by PULSE Friday 30th September 2011

 

Comparison of the clinical performance of an HPV mRNA test and an HPV DNA test
21 September 2011

New tests detecting HPV E6/E7 mRNA are emerging, claiming to be more specific for detecting high-grade disease. We evaluated the clinical performance of two HPV tests

We evaluated the clinical performance of two HPV tests: the Linear Array HPV genotyping test (LA) detecting HPV DNA from 37 oncogenic and non-oncogenic HPV types and the Aptima HPV assay detecting E6/E7 mRNA from 14 oncogenic HPV types.

Cytopathology : M. Waldstrom¹,  D. Ornskov²

Article first published online: 20 SEP 2011

Quality control in cervicovaginal cytology by cytohistological correlation
21 September 2011

IUCD may provide some protection from cervical cancer
19 September 2011

Contrary to popular belief, intrauterine contraceptive devices might actually protect women against developing cervical cancer even though they don't stop the infection that commonly leads to the disease, according to the results of an international study.

While IUDs, also known as coils, are unlikely to be recommended as way of preventing cervical cancer -- the second most common form of cancer in women worldwide -- the research should reassure women and their doctors that using them carries no added risk of the disease.

 

Spanish researchers who studied 20,000 women found that those with a history of using IUDs were no less likely than women who don't to contract the human papillomavirus (HPV) that causes cervical cancer, but they had only around half the risk of developing the cancer itself.

The scientists think possible explanations for the protective effect of IUDs could be that the process of inserting or removing them destroys pre-cancerous cells, or that it causes some kind of inflammation that prompts a long-lasting immune response and prevents the HPV from progressing.

 

"It was a little unexpected," Xavier Castellsague of the Catalan Institute of Oncology in Barcelona said in a telephone interview. "The data (available) before we did this study were very inconsistent, so we didn't expect to find such a strong association with this protective effect."

 

Cancer of the cervix is the second most common cancer in women across the world, with about 500,000 new cases and 250,000 deaths each year, according to the World Health Organization.

 

Virtually all cervical cancer cases are linked to genital infection with HPV, which is the most common viral infection of the reproductive tract.

 

Drugmakers Merck and GlaxoSmithKline have vaccines that protect against HPV and many wealthy and some developing countries have started nationwide immunization programs for girls to prevent more cases of cervical cancer.

An IUD is a plastic and copper or hormone-containing contraceptive device that is placed in the uterus to prevent sperm from joining with an egg.

 

Previous studies have shown that using coils can protect women against another type of cancer called endometrial cancer, but until now it was not clear whether they could also have an effect on the risk of cervical cancer.

 

Castellsague's team, whose study was published in the Lancet Oncology journal on Tuesday, analyzed data from 10 case-control studies of cervical cancer done in eight countries and 16 HPV prevalence surveys in women from four continents. The findings were adjusted for the number of sexual partners and other confounding factors.

 

The results show that coil use did not affect the risk of HPV infection, but was linked to a markedly lower risk of cervix cancer for both major types of the disease -- reducing the likelihood of developing squamous-cell carcinoma by 44 percent and adenocarcinoma or adenosquamous carcinoma by 54 percent.

 

The length of time that women used an IUD did not significantly alter the risk, the researchers said. They found the risk was reduced by nearly half in the first year of use and the protective effect remained significant even after 10 years.

"IUDs are not inert devices," Castellsague said. "Our speculation is that they act as a foreign body and stimulate inflammatory changes that prevent the HPV infection from persisting and progressing to more advanced stages.

"Lancet Oncology, online September 13, 2011

 

'Smart' cancer drug only activates on contact with tumours
19 September 2011

Cancer researchers at the University of Bradford in the UK have created a treatment that only activates itself once it touches a tumor, thereby saving healthy cells from being destroyed, reports Wired UK's Duncan Geere.

Cancer researchers at the University of Bradford have developed a treatment that only activates when it reaches a tumour, reducing damage to healthy cells.

The drug is based on colchicine -- a compound derived from the autumn crocus The colchicine is attached to a string of seven amino acids, which are cleaved off when they meet a particular class of enzyme (matrix metalloproteinases) that are only found in tumour environments, allowing the drug to activate.

The compound then starves the tumour to death by destroying its blood vessels, a process known as haemorrhagic necrosis. Previous treatments have focused on preventing growth of new blood vessels, but the University of Bradford's Kevin Adam'said that this is the first attempt at removing existing blood vessels.

Tests on mice have shown a 70 percent cure rate after a single dose on 4 different types of cancer. The remaining 30 percent of animals responded to the treatment, but weren't cured outright. Using the enzyme as a trigger means that it can also target secondary tumours caused by the cancer spreading through the body .The drug is a relatively small molecule, meaning that it can be synthesised easily. Laurence Patterson from the University of Bradford's Institute for Cancer Therapeutics said: "What we've designed is effectively a "smart bomb" that can be targeted directly at any solid tumour to kill it without appearing to harm healthy tissue."

By Duncan Geere wired.co.uk  16th September 2011

Evaluation of a completely automated tissue-sectioning machine for paraffin blocks
08 September 2011

Maristela L Onozato, Stephen Hammond, Mark Merren, Yukako Yagi J Clin Pathol published 7 September 2011, 10.1136/jclinpath-2011-200205

Tissue-sectioning automation can be a resourceful tool in processing anatomical pathology specimens. The advantages of an automated system compared with traditional manual sectioning are the invariable thickness, uniform orientation and fewer tissue-sectioning artefacts. This short report presents the design of an automated tissue-sectioning device and compares the sectioned specimens with normal manual tissue sectioning performed by an experienced histology technician. The automated system was easy to use, safe and the sectioned material showed acceptable quality with well-preserved morphology and tissue antigenicity. It is expected that the turnaround time will be improved in the near future.

Outcomes of pregnant patients with Pap smears classified as atypical glandular cells
19 August 2011

The incidence of cervical cancers increases with age. Due to the trend of increasing age of first pregnancy, abnormal Pap smears including those classified as atypical glandular cells (AGC) are being found more often in early pregnancy.

Methods: The study included 17 patients referred to us in early pregnancy with Pap smears reported as AGC: 11 not otherwise specified (AGC-NOS), five favour neoplasia (AGC-FN) and one adenocarcinoma in situ (AIS). Thirty-one with high-grade SIL (HSIL) Pap smears confirmed on punch biopsy in early pregnancy comprised a control group. Human papillomavirus (HPV) positivity was found in seven patients with persistent AGC-NOS (including all four who had CIN3 postpartum). All the women were initially examined by expert colposcopy and those with AGC-FN or AIS smears also by transrectal ultrasound to exclude invasive endocervical cancer. Follow-up controls were carried out every 8–12 weeks and, if there were no signs of progression, revaluation was scheduled 6–8 weeks after delivery.

Results: The mean age of the women was 31.4 years. Conization in one patient in the study group was performed in the 16th week of pregnancy due to colposcopic signs of microinvasive squamous cell cancer confirmed on histology. Progression to invasive cancer was not found in any of the other 16 patients in the study group or in the control group. Cervical intraepithelial neoplasia or AIS was confirmed postpartum by conization or punch biopsy in 47.1% (8/17) of patients in the study group and, in 77.4% (24/31) of patients in the control group.

Conclusions: Conservative management of women with AGC in pregnancy is safe where invasive cancer is excluded. As histological verification of glandular pre-cancerous lesions by punch biopsy is not reliable and the postpartum regression rate cannot be determined precisely, conization should be performed in all cases with AGC-FN or AIS. Triage of persistent AGC-NOS with HPV testing is useful in distinguishing significant underlying

 

 

J. Slama, P. Freitag, P. Dundr, J. Duskova, D. Fischerova, M. Zikan, I. Pinkavova and D. Cibula Outcomes of pregnant patients with Pap smears classified as atypical glandular cells  - Cytopathology

Labs Should Track 'Stealthy' Trend of Payors Buying Hospitals
21 July 2011

"The nation’s largest health insurers have begun, in the last year, a program to acquire physician groups and hospitals around the nation," according to G2.

Although still at an early stage, this signals a longer term strategy to control costs through tighter management of clinical practice."As a result, hospital labs "should keep watch for news of acquisition activity, and consider collaborating with clinicians to plan for clinical care pathways."

One example is United Healthcare, one of the nation's largest payors, whose health-services division is "quietly taking control" of doctors in several areas of the country who treat patients subscribed to its plans.After buying the practices, United "launches physician-management companies, for example," G2 said.

"There is definitely a national land grab over primary care physicians," G2 quoted Ted Schwab, partner at management consulting firm Oliver Wyman - G2 Intelligence Advancing the Business of Diagnostic Medicine July 15th 2011

Comment:

Does this US model seem familiar to the model being launched in the UK ?

GP consortium may be in control in the first instance but then the worm will turn ?

---

Roche Acquiring Cervical Cancer Test Developer MTM Laboratories for up to $269M
20 July 2011

Roche today announced an agreement to acquire MTM Laboratories for up to €190 million ($269 million) in a deal that expands Roche's capabilities in cervical cancer testing.

Roche will pay an upfront fee of €130 million and up to €60 million in milestone payments. Upon completion of the acquisition, MTM will become part of Roche's Tissue Diagnostics business unit. Roche said it expects to close the deal in the coming weeks.

Based in Heidelberg, Germany, MTM has developed tests for the detection of cervical cancer. Its lead products are the CINtec Plus Cytology kit for detecting the overexpression of p16 in cervical Pap smears for identifying pre-cancerous lesions and CINtec Histology for detecting high-grade cervical intraepithelial neoplasia and cervical carcinoma in biopsy samples.

The company plans to begin a clinical trial for its cytology test, CINtec Plus, in preparation of an FDA submission in the latter part of 2012. If approved, the test would move MTM into the cervical disease screening market.

According to Silverman, cervical cancer represents probably the largest cancer screening opportunity in the world for women, with about 150 million episodes every year. Of that, however, only about 1 percent of patients have cervical cancer.

While HR-HPV has been associated with cervical cancer, not all cases of high-risk HPV infection result in cervical cancer, and the vast majority of women with high-risk HPV don't get cervical cancer.

In the US, about 15 percent of women have high-risk HPV. "Obviously, they're not all getting cervical cancer. Most of the time it's a transient infection," Silverman said.

What is needed are markers that are specific for high-grade cervical disease that could become cancerous if undetected, and not just a risk factor. That's where MTM Laboratories and its technology comes in.

 

Risk of significant gynaecological pathology in women with ?glandular neoplasia on cervical cytology
13 July 2011

To review the risk of pre-invasive and invasive gynaecological pathology in women referred with cervical cytology reporting ?glandular neoplasia.

Conclusion :At least CIN2 was found in 81.5% in women referred with cervical cytology reporting ?glandular neoplasia. A thorough evaluation of the whole genital tract is needed if colposcopy is negative.

 

 

A. Talaat, D. Brinkmann, J. Dhundee, Y. Hana, J. Bevan, R. Irvine, S. Bailey and R. Woolas - Cytopathology

Work placements in labs are like gold dust
13 July 2011

says diane Garnham CEO of the UK Science Council.In a column in the New Scientist's Big Worldwide blog,Garnham writes that a new Science Council report shows that while scientific employers view work placements and internships as a great way for students to learn hands on science there arent enough opportunities.

This Week in the British Medical Journal
08 July 2011

In the British Medical Journal this week: a primer on endometrial cancer, and a debate over cancer survival statistics.