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LRCTC News - 2011

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

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

Over the past 60 years, U.S. mortality from cervical cancer has dropped by 70%, thanks to a successful screening program. In 1995, the American College of Obstetricians and Gynecologists (ACOG) recommended screening with the Papanicolaou (Pap) smear and pelvic examination at the initiation of sexual activity or by 18 years of age and annually thereafter. Although not evidence-based, this guideline was easy to remember, timed to coincide with the onset of legal adulthood, and well received by patients and clinicians. Linking the Pap smear to an annual visit, and often to the provision of other health care services such as contraception, breast care, and blood-pressure checks, made the patient likely to comply and the physician likely to remember to offer the test as part of routine care. Furthermore, although the Pap smear's sensitivity is poor — roughly 50 to 60% — the frequency of repetition made it likely that in screened patients, an abnormality missed one year would be found the next. Hence, the system worked.

In 2002 and 2003, the ACOG, the American Cancer Society (ACS), and the U.S. Preventive Services Task Force (USPSTF) all issued guidelines addressing many issues related to screening. In 2006, the American Society for Colposcopy and Cervical Pathology (ASCCP) issued management guidelines. Despite being “evidence-based,” these guidelines were different from one another, complicated, and hard to remember. Furthermore, the combination of a Pap smear with a test for human papillomavirus (HPV cotesting), which was addressed in these guidelines, was just being approved by the Food and Drug Administration (FDA) — on the basis of minimal clinical evidence that it added value. Despite recommendations indicating that Pap–HPV cotesting should be performed no more frequently than every 3 years because of its high added cost and limited additional clinical value, many patients, clinicians, and laboratories began cotesting annually.

Between 2009 and 2011, the same organizations, as well as American Society for Clinical Pathology (ASCP),reconvened expert panels to reevaluate the evidence and issue new guidelines. Again, there are some differences of opinion and interpretation. There are, however, many points of agreement (see Summary of Recommendations for Cervical-Cancer Screening.) and much opportunity to use the existing evidence to maintain a high-quality cervical-cancer prevention program that also safely addresses cost concerns.

Cervical cancer is rare before 20 years of age, and the incidence doesn't start to rise significantly until women reach the age of 25 or 30. Most cancers detected in screened women tend to be early-stage, so those found through screening are largely curable. For many women with early-stage disease, less-radical, fertility-sparing procedures can be curative, so even if early-stage cancers are detected, morbidity and mortality may be minimal.

Therefore, in 2009, the ACOG recommended that screening for “average-risk” women begin at the age of 21. Although the expert groups all agree that cervical cancer is rare before that age, they define high-risk younger groups somewhat differently; the ACOG defines average-risk women as immunocompetent women. Eliminating earlier screening averts overdiagnosis in young women based on transient cervical changes that their healthy immune systems would generally clear — and thereby also averts painful, costly, and possibly harmful procedures. Because there are no large prospective cohorts of immunocompromised patients, the USPSTF, which tends to be most rigorous in its evidence review, states that there is insufficient information for it to clearly recommend that screening should start before the age of 21 in immunosuppressed patients, but it offers the option of screening within 3 years after the onset of sexual activity, or by the age of 21.

Studies consistently show that for previously well-screened healthy women 30 years of age or older, the interval between Pap screenings can be lengthened to 3 years without significantly increasing their risk of cancer. It's also known that when screening takes place only every 5 years, or when women with abnormal Pap tests are not correctly triaged and treated to prevent cervical dysplasia from progressing to cancer, cancer rates increase. For women between 20 and 30 years of age, the optimal frequency is less well studied, but given the poor sensitivity of any single Pap test, the goal is to obtain at least two consecutive normal Pap results during this period to ensure that there are no missed opportunities for detecting and treating a precancerous lesion before lengthening the interval.

All the evidence and guidelines agree that HPV testing has no role in adolescents and should be performed in women 21 to 30 years of age only if a Pap test reveals atypical squamous cells of undetermined significance, an approach referred to as reflex testing. They also agree on reflex HPV testing for women 30 years of age or older under the same conditions. It is recommended that laboratories and clinicians not perform HPV screening in adolescents and that they use it only as a reflex test in women in their 20s.

The USPSTF, ACOG, and ASCCP–ACS–ASCP vary dramatically on whether evidence supports HPV cotesting for women 30 years of age or older. The USPSTF argues that Pap testing every 3 years for women over 30 is both safe and more cost-effective than cotesting and that no data support cotesting at the current screening intervals. It seems reasonable to use Pap testing alone every 3 years in this age group, unless the clinician seeks reassurance about lengthening the interval for a particular woman — for instance, if she has an uncertain Pap history or impaired immune status or may have difficulty complying with returning in 3 years. In such cases, HPV testing could be added or the Pap-testing interval shortened.

There is general agreement that in well-screened, low-risk women with no history of cancer or high-grade precancerous lesions, there comes a point when additional screening confers little added benefit. The USPSTF, ASCCP, and ACS agree on 65 as the age to stop screening such women. If the clinician cannot document a history of three normal Pap tests within the previous 10 years, then a Pap test should be obtained. If a patient has vaginal bleeding, vulvar discomfort, or other gynecologic or urologic symptoms, a complete pelvic examination and appropriate diagnostic testing should be performed. Furthermore, vaginal cancer is rare among women who have undergone hysterectomy, and all the guidelines agree that if such women are otherwise healthy and have no history of cancer or dysplasia, vaginal Pap testing may be discontinued.

In patients who have been treated for high-grade dysplasia, the risk of cervical cancer is increased by a factor of two to three for at least 20 years, but the risk of dying from cervical cancer is low, since most cancers are diagnosed at an early stage. Because it has long been the standard of care to screen these patients annually, we don't have good prospective data on whether this more frequent testing has contributed to early cancer diagnoses. Given that mortality rates have remained low with current practices, however, all groups recommend screening this population for at least 20 years after treatment.

Increasing screening in previously unscreened populations will further reduce the incidence of cervical cancer and related mortality. Reaching out to patients who face cultural, language, or educational barriers to care is important. Creating systems to remind clinicians that patients who come for episodic care must have appropriate cancer-screening tests is essential. Finally, making the guidelines for managing abnormalities easier for patients and clinicians to follow is important for both optimizing outcomes and containing costs for unnecessary referrals and treatment.

Health care is a limited resource, and providing the best care at the best price will become increasingly important. We need to use and understand actual data about risk and the long-term effects and costs of various strategies. Experts are often in the best position to review the data and make recommendations, but different expert panels may interpret data differently and emphasize different results in making their decisions. And even with the best consensus guidelines, some clinical judgment and personalized attention to each patient remains necessary.

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).

Summary

Background

Cervical intraepithelial neoplasia grade 2 or greater (CIN2+) is the surrogate endpoint used in licensure trials of human papillomavirus (HPV) vaccines. Vaccine efficacy against CIN3+, the immediate precursor to invasive cervical cancer, is more difficult to measure because of its lower incidence, but provides the most stringent evidence of potential cancer prevention. 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).

Methods

Healthy women aged 15–25 years with no more than six lifetime sexual partners were included in PATRICIA, irrespective of their baseline HPV DNA status, HPV-16 or HPV-18 serostatus, or cytology. Women were randomly assigned (1:1) to receive an HPV-16/18 AS04-adjuvanted vaccine or a control hepatitis A vaccine via an internet-based central randomisation system using a minimisation algorithm to account for age ranges and study sites. The patients and study investigators were masked to allocated vaccine. The primary endpoint of PATRICIA has been reported previously. In the present end-of-study analysis, we focus on CIN3+ and AIS in the populations of most clinical interest, the total vaccinated cohort (TVC) and the TVC-naive. The TVC comprised all women who received at least one vaccine dose, approximating catch-up populations and including sexually active women (vaccine n=9319; control=9325). The TVC-naive comprised women with no evidence of oncogenic HPV infection at baseline, approximating early adolescent HPV exposure (vaccine n=5824; control=5820). This study is registered with ClinicalTrials.gov, number NCT00122681.

Findings

Vaccine efficacy against CIN3+ associated with HPV-16/18 was 100% (95% CI 85·5–100) in the TVC-naive and 45·7% (22·9–62·2) in the TVC. Vaccine efficacy against all CIN3+ (irrespective of HPV type in the lesion and including lesions with no HPV DNA detected) was 93·2% (78·9–98·7) in the TVC-naive and 45·6% (28·8–58·7) in the TVC. In the TVC-naive, vaccine efficacy against all CIN3+ was higher than 90% in all age groups. In the TVC, vaccine efficacy against all CIN3+ and CIN3+ associated with HPV-16/18 was highest in the 15–17 year age group and progressively decreased in the 18–20 year and 21–25 year age groups. Vaccine efficacy against all AIS was 100% (31·0–100) and 76·9% (16·0–95·8) in the TVC-naive and TVC, respectively. Serious adverse events occurred in 835 (9·0%) and 829 (8·9%) women in the vaccine and control groups, respectively; only ten events (0·1%) and five events (0·1%), respectively, were considered to be related to vaccination.

Interpretation

PATRICIA end-of-study results show excellent vaccine efficacy against CIN3+ and AIS irrespective of HPV DNA in the lesion. Population-based vaccination that incorporates the HPV-16/18 vaccine and high coverage of early adolescents might have the potential to substantially reduce the incidence of cervical cancer.

Funding

GlaxoSmithKline Biologicals.

Matti Lehtinen ProfPhD et al

The Lancet Oncology http://dx.doi.org/10.1016/S1470-2045(11)70286-8

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.

Background

Vaginal self-sampling for human papillomavirus (HPV) DNA testing could increase rates of screening participation. In clinic-based settings, vaginal HPV testing is at least as sensitive as cytology for detecting cervical intraepithelial neoplasia (CIN) grade 2 or worse; however, effectiveness in home settings is unknown. We aimed to establish the relative sensitivity and positive predictive value for HPV screening of vaginal samples self-collected at home as compared with clinic-based cervical cytology.

Methods

We did a community-based, randomised equivalence trial in Mexican women of low socioeconomic status aged 25—65 years. Participants came from 540 medically underserved, predominantly rural communities in Morelos, Guerrero, and the state of Mexico. Our primary endpoint was CIN 2 or worse, detected by colposcopy. We used a computer-generated randomisation sequence to randomly allocate patients to HPV screening or cervical cytology. Eight community nurses who were masked to patient allocation received daily lists of the women's names and addresses, and did the assigned home visits. We referred women with positive results in either test to colposcopy. We did per-protocol and intention-to-screen analyses. This trial was registered with the Instituto Nacional de Salud Pública, Mexico, INSP number 590.

Findings

12 330 women were randomly allocated to HPV screening and 12 731 to cervical cytology; 9202 women in the HPV screening group adhered to the protocol, as did 11 054 in the cervical cytology group. HPV prevalence was 9·8% (95% CI 9·1—10·4) and abnormal cytology rate was 0·38% (0·23—0·45). HPV testing identified 117·4 women with CIN 2 or worse per 10 000 (95·2—139·5) compared with 34·4 women with CIN 2 or worse per 10 000 (23·4—45·3) identified by cytology; the relative sensitivity of HPV testing was 3·4 times greater (2·4—4·9). Similarly, HPV testing detected 4·2 times (1·9—9·2) more invasive cancers than did cytology (30·4 per 10 000 [19·1—41·7] vs 7·2 per 10 000 [2·2—12·3]). The positive predictive value of HPV testing for CIN 2 or worse was 12·2% (9·9—14·5) compared with 90·5% (61·7—100) for cytology.

Interpretation

Despite the much lower positive predictive value for HPV testing of self-collected vaginal specimens compared with cytology, such testing might be preferred for detecting CIN 2 or worse in low-resource settings where restricted infrastructure reduces the effectiveness of cytology screening programmes. Because women at these sites will be screened only a few times in their lives, the high sensitivity of a HPV screen is of paramount importance.

Funding

Instituto Nacional de Salud Pública, the Health Ministry of Mexico, QiAGEN Corp
 
Prof Eduardo Lazcano-Ponce PhD  et al
 
The Lancet, Early Online Publication, 2 November 2011
doi:10.1016/S0140-6736(11)61522-5

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.

Objective  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.

Design  A retrospective follow-up study within the NHS HPV/LBC pilot studies.

Setting  The NHS Cervical Screening Programme in England.

Population  A total of 1063 HPV-positive women with borderline or mild dyskaryosis who were negative at colposcopy from three sites within the NHS HPV/liquid-based cytology (LBC) pilot studies.

Methods  HPV triage took place in 2001/02. In 2009 all information on additional management on HPV-positive/colposcopy-negative women was requested. The rate of disease following a negative colposcopy was calculated, and survival analysis was used to determine whether the grade of referral cytology impacted on risk of subsequent disease. Results were compared with those in women from the same population who had not been HPV triaged.

Main outcome measures  Incident CIN2 or worse during follow up.

Results  Of 1063 eligible women 965 had documented follow up. The cumulative rate of CIN2+ at 3 years in these women was 4.4% (95% CI 4.0–7.0%); the median time from normal colposcopy to final result was 27 months. There was no significant increase in the risk of future disease associated with age or initial cytology result.

Conclusions  The rate of subsequent high-grade CIN among colposcopically negative triaged women was sufficiently low to justify return to routine recall.

 

RS Kelly1,

  • P Walker2,
  • H Kitchener3,
  • SM Moss4
  • DOI: 10.1111/j.1471-0528.2011.02970.x
  •  

    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

    The proportion of women in their 20s diagnosed with cervical cancer in England has risen significantly since the early 1990s, research reveals.

    While about five women per 100,000 in the age group (a total of about 192 a year between 1992 and 1996) were found to have the disease, this rose to six per 100,000 in 2002-6 (197 a year) and nine per 100,000 in 2006-7 (303 cases). The rise has occurred in a period during which overall incidence of cervical cancer has dropped by nearly a third. About 900 women in England a year die of cervical cancer.

    A study funded by Cancer Research UK outlining the figures will be presented at the National Cancer Research Institute conference in Liverpool.

    Experts said more encouragement must be given for girls of 12 and 13 to be vaccinated against the human papilloma virus (HPV), which can trigger the disease, and for women in their late 20s and 30s to be screened, even though cancer prevention figures are not as good as those for older women.

    Public health messages should also continue to increase understanding of HPV as well as cancer risks from smoking and some sexual behaviour. The earlier a woman starts having sex and the more men she has sex with, the more likely she is to pick up an infection with a cancer-causing strain of HPV, but this does not mean women who get cervical cancer have it because they were promiscuous. Sleeping only with one man who had had many partners would increase a woman's risk of infection as well.

    Hazel Nunn, head of evidence and health information at Cancer Research UK, said: "These figures show just how crucial it is for all 12- to 13-year-old girls to have the HPV vaccination. HPV is a very common infection and the major cause of cervical cancer. The HPV vaccine protects against two strains of the infection and is most effective when given to women before they are exposed to the virus.

    "Whatever your age, if you have any bleeding between periods, during sex or after the menopause, you should go to your GP."

    The study covered cervical cancer incidence from 1982 to 2007. It fell among 20- to 29-year-olds in England after the introduction of screening in 1988 before rising again as incidence in other age groups fell. In women aged 50-79 years it dropped from about 17 per 100,000 (6,263 cases) between 1992 and 1996 to just over 10 per 100,000 (4,089 cases) between 2002-6.

    Since 2003, only women over 25 have routinely been offered screening every three years because it is known to be less effective among younger women. In women under 40, cells are liable to change far more quickly than in older women, where screening up to the age of 64 is offered every five years. Between 60% and 70% of 25- to 35-year-olds take up the offer of screening while the figure for 50- to 64-year-olds is about 80%. Even through screening is recommended, it is thought to prevent only about 45% of cancer cases among under-30s, compared with 75% among 50- to 60-year-olds.

    A programme to immunise schoolgirls against cervical cancer has proved successful since it began in 2008. Girls aged 12 and 13 who volunteer receive three jabs. Provisional data from the Department of Health up to the end of June 2011 shows that about 77% of girls in this age group had received the full course of HPV vaccine in the 2010/11 academic year in England. The final figures are likely to be higher when the collection is completed.

    Figures for 2009/10 suggested that three in five 12- to 19-year-olds had completed the course.

    Cervical screening detects a pre-cancerous condition so women who test positive and are treated do not appear in incidence figures.

    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.

    Methods:  We identified 369 consecutive PreservCyt samples diagnosed with ASC-US tested for HPV DNA using the LA test. The Aptima HPV test was performed on residual material in the same vial. Follow-up of 325 women was available. The gold standard used was histologically confirmed cervical intraepithelial neoplasia (CIN) grade 2+ or 3+.

    Results:  LA and Aptima HPV assays were positive in 44.3% and 31.7% of the cases, respectively. The concordance was 81.2%. The two tests had identical sensitivity for detecting CIN3+ [92.6% (95% CI, 75.7–99.1)] but the Aptima HPV assay showed a significantly better specificity of 73.8% (95% CI, 68.5–78.7) versus 60.1% (95% CI, 54.3–65.7) for LA for detecting CIN3+. When using CIN2+ as the gold standard the sensitivity for LA was higher than for the Aptima HPV assay [93.8% (95% CI, 82.8–98.7) versus 87.5% (95% CI, 74.8–95.3)], but the specificity was higher for the Aptima HPV assay: 78.0% (95% CI, 72.6–82.7) versus 64.3% (95% CI, 58.3–69.9).

    Conclusions:  Both tests showed good and equal clinical sensitivities for detecting CIN3+, but the Aptima HPV assay had significantly higher specificity for detecting CIN2+ and CIN3+ in women aged 30 years or older with ASC-US.

    Cytopathology : M. Waldstrom1,  D. Ornskov2

    Article first published online: 20 SEP 2011

    Quality control in cervicovaginal cytology by cytohistological correlation
    21 September 2011

    Objective:  Frequent studies attest to the correlation of cytological interpretations with defined histopathological entities. Nevertheless, as part of quality control, cytology laboratories are required to compare Papanicolaou smear reports with those of cervical biopsies to search for discrepancies. We have attempted to determine and categorize the causes of existing discrepancies in our laboratory in order to clarify the source of errors.

    Methods:  We reviewed 670 cervical smears that were paired with subsequent punch biopsy or endocervical curettage samples, obtained within 2 months of the cytology, and found out that 60 smear-biopsy pairs were discrepant regarding the diagnosis. These cases were categorized into four error groups after careful re-evaluation of the original smear and biopsy slides.

    Results:  In 51 (85%) of 60 cervical smear-biopsy pairs with reports that disagreed, the initial diagnoses of both cervical smear and biopsy were confirmed by the review opinion; in these cases, cytology and biopsy ‘sampling errors’ were responsible for 40 and 11 instances of discrepancy, respectively. Seven cases (11.1%) were discrepant due to ‘smear interpretation errors’ and consisted of five cases with initial under-diagnosis and two cases with initial over-diagnosis. One case (1.7%) was due to ‘screener error’. In another case, discordance was due to cervical ‘biopsy interpretation error’, with initial over-diagnosis as squamous intraepithelial lesion.

    Conclusion:  In this retrospective study, we determined the causes of cytohistological discrepancies in cervical samples. The main explanation for discrepancy was ‘sampling error’.

    Cytopathology:   N. Izadi-Mood, S. Sarmadi, S. Sanii

    Article first published online: 19 SEP 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.

    I work in a large diagnostic laboratory in the UK and we recieve requests on a daily basis for work experience/ internships. The problem is the legalities surrounding the whole issue of employment for no remuneration. We often identify areas of work that require short to medium term commitment that cannot be undertaken by existing staff due to time constraints but would suit someone requiring experience/consolidation of what they had learnt at university. However employment law is very clear that this should not be work that could be undertaken by a paid employee which is where the difficulties lie. The fact that interns can also sue for payment up to 6 years retrospectively does not encourage facilities to offer these positions in a hurry.

    Its a mad world................... IP

    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.

    Nobel Prize Winner to Test Cancer-Causing Bug in Drinkable Flu Vaccine
    30 June 2011

    By Simeon Bennett - Jun 28, 2011 3:00 PM GMT+0100 .

    Barry J. Marshall, the Australian scientist who won a Nobel Prize for identifying a cancer-causing stomach bacterium, plans to start a trial next year using the bug in a drinkable flu vaccine.

    Marshall, the founder, scientific director and majority owner of closely held Ondek Ltd., plans to test the vaccine in at least 30 people in the U.S., and expects results from the trial by mid-2013, he said in a telephone interview yesterday.

    Ondek, based in Perth, Australia, aims to harness the ability of the bacterium Helicobacter pylori to colonize the stomach. The bug’s harmful genes will be removed and those from influenza and other viruses will be inserted to stimulate an immune response. If successful, the vaccine would be sold as a freeze-dried powder or a capsule, sidestepping the inconvenience and side effects of injections, Marshall said.

    “We’re focusing on flu because we think that would be attractive to investors,” Marshall said. “That’s the big market.”

    A preliminary study, in which healthy volunteers received disarmed strains of the bacterium in a beef broth, showed some strains were capable of safely colonizing the gut, proving the concept is feasible, Marshall said. The strains weren’t carrying any viral genes. He presented the results at a conference in Singapore on June 23.

    The flu-vaccine market reached about $3.7 billion last year, Ondek said on its website. The company, which has about 20 investors, has raised more than A$3 million ($3.1 million) of a targeted A$5 million for the next trial and is seeking more funding, Marshall said.

    “In Australia people are more comfortable with mining investments and will put massive amounts of money into holes in the ground,” he said. “We don’t have a lot of mature investors yet who’ve had a good experience in biotechnology, and can see that it’s a similar type of risk-benefit ratio.”

    Increasing rates of cervical cancer in young women in England
    30 June 2011

    16 June 2011 : Interrogation of a UK national cancer registration database has revealed a significant increase in cervical cancer rates in 20-29 year-olds in the period 1992-2006.

    http://www.nature.com/bjc/journal/vaop/ncurrent/full/bjc2011196a.html

    Formaldehyde substitute fixatives: effects on nucleic acid preservation
    30 June 2011

    Cathy B Moelans, Daphne Oostenrijk, Michiel J Moons, Paul J van Diest Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands J Clin Pathol doi:10.1136/jclinpath-2011-200152

    Abstract

    Aims In surgical pathology, formalin-fixed paraffin-embedded tissues are increasingly being used as a source of DNA and RNA for molecular assays in addition to histopathological evaluation. However, the commonly used formalin fixative is carcinogenic, and its crosslinking impairs DNA and RNA quality.

    Methods The suitability of three new presumably less toxic, crosslinking (F-Solv) and non-crosslinking (FineFIX, RCL2) alcohol-based fixatives was tested for routine molecular pathology in comparison with neutral buffered formalin (NBF) as gold standard. Size ladder PCR, epidermal growth factor receptor sequence analysis, microsatellite instability (MSI), chromogenic (CISH), fluorescence in situ hybridisation (FISH) and qPCR were performed.

    Results The alcohol-based non-crosslinking fixatives (FineFIX and RCL2) resulted in a higher DNA yield and quality compared with crosslinking fixatives (NBF and F-Solv). Size ladder PCR resulted in a shorter amplicon size (300 bp) for both crosslinking fixatives compared with the non-crosslinking fixatives (400 bp). All four fixatives were directly applicable for MSI and epidermal growth factor receptor sequence analysis. All fixatives except F-Solv showed clear signals in CISH and FISH. RNA yield and quality were superior after non-crosslinking fixation. qPCR resulted in lower Ct values for RCL2 and FineFIX.

    Conclusion The alcohol-based non-crosslinking fixatives performed better than crosslinking fixatives with regard to DNA and RNA yield, quality and applicability in molecular diagnostics. Given the higher yield, less starting material may be necessary, thereby increasing the applicability of biopsies for molecular studies.

    An investigation of adequate volume for the diagnosis of malignancy in pleural fluids
    30 June 2011

    S. C. Thomas, L. R. R. Davidson, M. E. McKean Cytopathology Volume 22, Issue 3, pages 179–184, June 2011

    Objective:  The cytological examination of pleural effusions is an important investigation in the diagnosis of malignancy. Maximizing the chances of identifying malignant effusions is therefore desirable. Recent Royal College of Pathologists guidelines, based on the British Society for Clinical Cytology codes of practice, have suggested that a minimum of 20 ml of pleural fluid is required for diagnostic purposes.

    Methods & Results:  We examined 2155 pleural fluids received over a 6-year period in order to define a minimum required volume for adequacy. By examining the plateau phase of a graph of threshold volumes for initial samples received for each patient (n = 1584) we determine that a minimum fluid volume of 25 ml is required and that more than 50 ml does not improve sensitivity.

    Conclusion:  Between 25 and 50 ml of fluid are required for the adequate assessment of pleural effusions for malignancy.
    View article...

    NHS Cancer Screening Programme
    08 June 2011

    15th December 2010 DOH published the NHS Operating Framework. It recommends HPV Triage (Low grades only) to be rolled out across England- London has set up a working party for a planned roll out.

    Cytology 14 day TAT
    08 June 2011

    12th January 2011 Cancer Strategy-Improving Outcomes: section 4.25 “November 2010 81% women were receiving their results within 14 days. As recommended by the Advisory Committee on Cervical Screening (ACCS) the threshold for achieving this has been set at 98%” Average cost saving of £100,000 saved per unit per year.

    A word on HPV Vaccines
    08 June 2011

    Cervarex (bivalent 16,18) was a bad decision claim sexual health experts.

    Dismay at UK government not choosing Gardasil quadrivalent vaccine.
    Cervarex does not protect against genital warts caused by HPV subtypes 6 & 11
    In contrast Australia chose Gardasil has seen a 47% drop in genital warts since immunisation began (UK spends circa £25 million pa on treatment warts)
        February 2011 www.bbc.co.uk/cancer/news/health
     

    Profile of Cervical Cancer in England Report - February 2011
    08 June 2011

    The National Cancer Intelligence Network and the NHS Cervical Screening Programme have produced a collaborative report detailing the current status of cervical cancer in England.