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Safe thresholds for HC2 HPV testing in primary screening

28 May 2011 : An analysis of HPV primary screening trials suggests that cut-off values for the HC2 test could be safely increased to 10rlu. False positive results would be greatly reduced without significantly compromising sensitivity.

£775m investment in NHS research planned

10 March 2011 : Up to £775 million of government funding is to be made available over the next five years for research aimed at delivering benefits to NHS patients.

"Logical and inevitable" move to HPV-based cervical cancer prevention

05 March 2011 : "The logical and inevitable move to HPV-based cervical cancer prevention strategies will require longer screening intervals that will disrupt current gynecologic and cytology laboratory practices built on frequent screening."

Unnecessary bureaucracy is crippling NHS research

17 January 2011 : Academy of Medical Sciences press release.

Urgent changes are required to the regulation and governance of health research in the UK because unnecessary delays, bureaucracy and complexity are stifling medical advances, without additional benefits to patient safety. A report by the Academy of Medical Sciences sets out a new regulatory and governance pathway that will increase the speed at which healthcare innovations become available to patients, whilst eliminating unnecessary bureaucracy.

Professor Sir Michael Rawlins FMedSci, Chair of the Academy of Medical Sciences working group that prepared the report, said:

“A fertile research environment is vital for the health
and wealth of the UK. The current system of regulation is making it increasingly difficult to initiate health research in the UK and is preventing patients from participating in studies.
This is ultimately denying patients early access to new drugs and hindering improvements to public health for the wider society.

“We have found unequivocal evidence that health research in this country is being jeopardised by a regulatory and governance framework that has become unnecessarily
complex and burdensome. Further, we received no evidence that this increased regulatory and governance burden has led to enhanced safeguards for participants in research. The
changes we propose will streamline and improve the process to create a better environment for research, while protecting the interests of patients and the public.”

The report recommends the establishment of a new independent Health Research Agency (HRA) to bring together existing approval processes. The Agency would work with regulatory and governance bodies in the devolved nations to develop an integrated approvals system
for the UK. The report recommends that the Department of Health should establish a new National Research Governance Service (NRGS) for England, to be housed within the HRA.
The NRGS would facilitate rapid approval of research studies conducted in single or multiple NHS sites by assuming responsibility for all study-wide checks that are currently duplicated by each participating NHS Trust.

Sir Michael added, “The delay in obtaining NHS permissions is a major failure of the current pathway and is the biggest single barrier to all types of health research studies. There is a
highly inefficient emphasis on process rather than outcomes, which has led to delays of over a year to gain permissions for simple studies. The UK has created nearly a quarter of the world’s top 100 medicines and its share of world citations in both the clinical and health sciences is currently second only to the US. However, recent data show a decline in the UK’s global share of clinical research activity. There is widespread agreement that the regulatory and governance framework is one of the main contributing factors to this decline. Implementing the changes outlined in the Academy’s
report will allow the UK to realise the health and wealth benefits of our world class health research base and maximise the value of our public, charitable and commercial investment.
Sir Michael Rawlins concluded, “It is vital that the HRA is established as soon as possible. To achieve its goals it will have to be a genuine single regulator and not a mere façade hiding the continuation of many separate existing bodies. We recommend that it is established as soon as possible to start making necessary changes to start making necessary changes right away and then confirmed in primary legislation in due course.”

On publication of the report, Professor Sir John Bell FRS FREng PMedSci, President of the Academy of Medical Sciences, said, “The UK has historically supported vibrant research intensive medical science industries and world-renowned academic medical science centres, but a cumbersome regulatory and governance environment is driving this work abroad. Health research must be subject to robust regulation that both protects patients and
facilitates globally-competitive research. This report sets out a realistic and achievable framework by which this can be achieved.”

Automation-assisted cytology no better than conventional screening

28 December 2010 : Hot on the heels of the MAVARIC trial showing no benefit of automation-assisted cervical cytology, a large RCT from Finland involving more than half a million cases has reached the same conclusion.

Rapid pre-screening more sensitive in LBC than conventional cytology

26 December 2010 : An analysis of over 50,000 slides pre- and post-conversion to liquid based cytology shows that rapid prescreening by LBC is significantly more sensitive for detecting cervical abnormalities (58.7 vs. 68.7%, p<0.001) than conventional cytology.

Acta Cytologica 201155:54–56
DOI: 10.1159/000320906

LBC improves detection of glandular abnormalities

12 December 2010 : Reporting rates for glandular neoplasia in 464,754 cervical samples reported at six UK laboratories in 12-month periods before and after the implementation of SurepathTM LBC processing are compared. The introduction of LBC processing is seen to have resulted in a significant increase in the detection rate for endocervical glandular neoplasia while maintaining high levels of reporting specificity. The authors suggest the following underlying reasons for the observed improvement in detection of endocervical glandular neoplasia:
1. More effective sampling of the endocervical canal as a result of changed sampling devices (from wooden spatulae to broom style samplers)
2. More representative transfer of cells from the sampling device to the liquid medium used for processing
3. Improved morphological presentation of endocervical abnormalities particularly evident with Surepath samples.

MAVARIC trial results

11 December 2010 : MAVARIC was a randomised controlled trial designed to investigate the utility of automation-assisted reading of cervical cytology slides.

73 266 liquid-based cytology samples were obtained from women aged 25–64 years undergoing primary cervical screening in the UK. Women were randomly assigned to receive either manual reading only or paired reading (automation-assisted reading and manual reading). In the paired arm, two automated systems were used—the ThinPrep Imaging System and the FocalPoint GS Imaging System. The primary outcome was sensitivity of automation-assisted reading relative to manual reading for the detection of underlying CIN2+ in the paired arm.

Automation-assisted reading was 8% less sensitive than manual reading and specificity increased by 0·6%. The inferior sensitivity of automation-assisted reading for the detection of CIN2+, combined with an inconsequential increase in specificity, suggests that automation-assisted reading cannot be recommended for primary cervical screening.

HPV RNA test equally sensitive but more specific than DNA testing

18 November 2010 : A study published in the International Journal of Cancer, an HPV RNA assay provided a better combination of sensitivity and specificity than HPV DNA- or cytology-based tests for cervical cancer screening.

The French APTIMA Screening Evaluation (FASE) study is the first screening study to compare liquid-based cytology, a Pap test widely used in cervical cancer screening, with the new RNA-based APTIMA HPV test and the DNA-based Hybrid Capture 2 test (HC2).

Commenting on the implications of the trial, Eric Lai, PhD, Gen-Probe’s senior vice president of Research and Development, said: “DNA tests detect the presence of the HPV virus, whereas APTIMA HPV targets biologically relevant markers active in transforming cervical cells. DNA tests are therefore more likely to pick up transient infections and lead to false positive results with respect to disease. This study showed that in a routine screening population, APTIMA HPV had the same sensitivity as a HPV DNA test, with the low false positive rate of cytology. This means women at risk of cervical cancer could be more accurately identified. At the same time, unnecessary colposcopies, office visits, over-treatment and the associated costs could be reduced. In addition, APTIMA HPV could decrease the patient anxiety caused by inappropriate diagnostic procedures.”

Performance of HPV testing as a primary screening test in China

14 November 2010 : A pooled analysis of primary HPV testing in over 30,000 women from 17 studies across China, concludes that HPV testing is significantly more sensitivie for the detection of CIN3 or worse than either cytology or visual inspection with acetic acid. By adopting a cutoff point for HPV positivity of 10pg/ml for women under the age of 35, instead of the manufacturer's recommendation of 1-2pg/ml, specificity was increased and a high sensitivity was maintained.

8 HPV types cause 90% of cervical cancers

29 October 2010 : A massive multinational study reported in Lancet Oncology has shown that HPV types 16, 18, 45, 33, 31, 52, 58, and 35 account for 91% of all cases of cervical cancer. It is likely that the next generation of cervical cancer vaccines will specifically include each of the 8 HPV types noted in this paper, since this will cover 90% of the cases of cervix cancer.

What is the best method of surveillance after treatment for CIN?

28 October 2010 : Conventional cytology apparently! Human papillomavirus testing and liquid-based cytology increases costs, but not effectiveness, compared with traditional approaches, according to a paper in the current issue of Obstet Gynecol

p16INK4a immunostaining as an alternative to histology review for reliable grading of cervical intraepithelial lesions

28 October 2010 : The use of p16INK4a immunohistochemistry significantly improves the accuracy of grading CIN lesions by a single pathologist, equalling an expert consensus diagnosis.

HPV Screen and Treat Intervention Effective in Cervical Cancer Prevention

21 October 2010 : A randomized trial in a resource-limited setting has shown that an HPV test-and-treat policy is more effective than visual inspection-and-treat in reducing the incidence of high grade CIN.

Study suggests automation-assisted cervical screening is valid

20 September 2010 : A randomised study from Finland comparing automation-assisted screening and conventional cytology hs shown no difference in cervical cancer risk between the two groups after six years of follow up. The authors suggest that both methods are valid for screening.

Controversy brews over benefits of screening a population vaccinated against HPV

26 August 2010 : Controversy has arisen over the potential impact on cervical cancer rates of reduced screening in a population vaccinated against HPV. A recent modeling study reported in The Lancet Infectious Diseases suggests that introduction of the vaccine is unlikely to lead to an increased incidence of cervical cancer as a result of diminished screening. However, a Finnish group disputes this conclusion by claiming that vaccinations alone will not prevent cervical cancer unless their efficacy is longer than 15 years. If the duration of efficacy is shorter and efficient boostering is not organised, the onset of the cancer in women is merely postponed and rates of cervical cancer will ultimately increase.

LBC no more sensitive than conventional cytology, even in hands of experts

26 August 2010 : This study challenges the claim that LBC improves the sensitivity for detection of CIN2+ compared with conventional cytology. A random sample of 818 LBC cases originally reported in the NTCC trial were blindly reviewed by three international cytology exerts.There was no significant difference between the accuracy of the experts and the original interpreters.

Grave prognosis of HPV 16/18 positivity in screened populations

24 August 2010 : Existing data on HPV type-specific risk is derived largely from unscreened populations. A case control study in a screened UK population indicates a considerable risk of subsequent invasive cervical cancer in women infected with HPV 16 and 18, particularly in women over 40.

FISH marker of CIN progression

21 August 2010 : A FISH assay comprised of chromosomal probes 8q24 and 3q26 to cervical cytology specimens confirms the positive correlation between increasing dysplasia and copy gains and shows promise as a marker in cervical disease progression.

"Paper smears" used to detect cervical HPV

07 August 2010 : A study from India has shown that HPV DNA can be effectively detected using a simple and inexpensive paper smear method for the dry collection of cervical specimens.

Diagnostic accuracy of guided cervical biopsies

05 August 2010 : A prospective study in which colposcopically guided cervical biopsies and cone excision were performed in a single procedure, the sensitivity and specificity of biopsies for detecting CIN2+ were 66.2% and 95.0%, respectively. While the positive predictive value was 98.5%, the negative predictive value was only 35.5%. So, cervical biopsies are reliable for confirming cytologically detected high grade disease but are relatively poor at excluding it.

'Screen young and old' message from Iceland.

23 July 2010 : An analysis of the Icelandic cervical screening programme concludes that, in the HPV vaccine era:
1. Screening should continue to start at age 20 years and stop at 69
2. The optimal age for catch-up HPV vaccination should be considered in the context of sexual practices
3. The age limit and screening intervals for HPV- vaccinated women should not be changed.

This "Editor's Choice" article is FREE for a limited time.

FUTURE I/II trial shows sustained HPV vaccine efficacy

23 July 2010 : FUTURE (Females United To Unilaterally Reduce Endo-ectocervical disease) was a randomized controlled trial studying the efficacy of the quadrivalent HPV vaccine Gardasil. The trial involved nearly 18000 women in 24 countries. The vaccine provided sustained protection (>95%) against low grade lesions attributable to vaccine HPV types (6, 11, 16, and 18) and a substantial reduction in the burden of these diseases through 42 months of follow-up. Protection against all low grade lesions (regardless of HPV type) was also sgnificant (30%, 75% and 48% for cervical, vulval and vaginal lesions, respectively).

Say hello to morpho-molecular cytology

21 July 2010 : A paper in Cancer Cytopathology describes a new automated technology in which cytology slides are consecutively scanned for morphological changes and genetic changes in the detection of lung cancer. The authors suggest its utility for mass screening.

HPV prevalence in England

18 July 2010 : An analysis of over 5000 cervical cytology samples and biopsies has confirmed the high prevalence of HPV 16 and/or 18 across multiple sites in England. This promises a high impact from HPV immunisation in due course.

The multidisciplinary colposcopy meeting: recommendations for future service provision and an analysis of clinical decision making

12 July 2010 : "When significant discrepancies exist between colposcopy, cytology and histopathology, then MDT discussion seems pertinent as MDT discussion can lead to the avoidance of over-treatment. To improve timeliness of treatment, MDT meetings should occur at least monthly. The results of each case discussion should be recorded in the patient case notes, the minutes of each meeting should be circulated to all MDT members and a letter describing MDT recommendations must be sent to the colposcopist responsible for patient care."

Clinical review of borderline glandular cells reported on liquid-based cervical cytology

12 July 2010 : "On the basis of our results, it would be considered acceptable to manage women [with borderline glandular cells] under 35 years of age with normal and satisfactory colposcopy conservatively. In women above 35 years of age, we would recommend a diagnostic 'large loop excision of the transformation zone' procedure, irrespective of the colposcopic findings"

Pilot study of HPV DNA and cytology testing in Mexican Social Security Program

12 July 2010 : HPV testing for cervical screening has been found to be over 50 per cent more sensitive than cytology in a community-based study in Mexico. This is the largest HPV primary screening study ever to be performed in a Latin American country and points to the readiness of HPV testing for large-scale implementation in Mexico.

Another study confirms high sensitivity of HPV screening

29 April 2010 : Reporting in this week's BMJ, a Finnish randomized controlled trial has confirmed the superior sensitivity of HPV testing compared with conventional cytology for cervical screening. These results are consistent with most of those previously reported.

TOMBOLA results at odds with other studies

18 April 2010 : Summary of commentary from: Arbyn M, Martin-Hirsch P, Wentzensen N. HPV-based triage of women showing a cervical cytology result of borderline or mild dyskaryosis. BJOG 2010117:641–644.

In TOMBOLA, the sensitivity of hrHPV triage of borderline and mild dyskaryosis was 69.9% and 75.2% for detection of underlying CIN2+ (see research item for 21st March 2010). All other studies, including the ASCUS-LSIL Triage Study (ALTS) showed substantially higher sensitivities.

The differences may be explained by differences in HPV test sensitivity or differences in outcome assessment. Notable in TOMBOLA was the reliance on community based histology outcomes, compared with the more stringent approaches to histological assessment in other studies. Overcalling of CIN1 or squamous metaplasia as CIN2 or CIN3 may mave been an important contributor to the observed results.

ThinPrep Imager higher sensitivity for low grade but not high grade abnormalities

14 April 2010 : A comparison of the sensitivity of the ThinPrep Imaging (TPI) system and conventional cytology for the detection of cellular abnormalities has given mixed results. TPI gave improved detection rates for low grade abnormalities but not for high grade.

NHSCSP 31 highlights

14 April 2010 : This publication is a critical review of four types of studies looking at screening and cervical cancer. In brief:

There is "no evidence that screening women aged 22–24 reduced the incidence of cervical cancer at ages 25–29 (OR 1.11, 95% CI 0.83–1.50)."

"The probability of regression for the entire cohort [of 13-22 year-olds with any lesion or HPV infection] was 61% (95% CI 53–70) at 12 months and 91% (95% CI 84–99) at 36 months’ follow up. Only 3% (95% CI 0.7–6.0) progressed to high grade disease."

"...progression rate [from CIN3 to cancer] within five years of diagnosis can be no greater than 1% per year and is more likely to be around 0.5% per year."

"...for every 100 women treated aged 20–24, at best one case of cancer is prevented that would not have been prevented had screening been delayed until age 25."

"...LLETZ was significantly associated with preterm delivery (relative risk (RR) = 1.70, 1.24–2.35), low birth weight."

"...the evidence published since 2002 shows little, if any, benefit from screening women under 25 as far as the prevention of cervical cancer or of advanced cervical cancer is concerned."

"...the Advisory Committee on Cervical Screening (England) was unanimous in its decision not to lower the age at first invitation from 25 to 20."

TOMBOLA trial throws doubts on the value of HPV triage

21 March 2010 : Numerous studies have shown that HPV testing is good at detecting abnormalities in women with low-grade tests and can reduce the number who need to be referred for treatment, especially in the over 35s. However, a recent publication in BJOG seems to cast doubt over the presumed benefits of HPV testing as a means of triage for low grade cytological abnormalities.

In the study 4439 women with borderline changes or mild dyskaryosis received an HPV test and were followed for three years. Outcome was determined by an exit colposcopy examination. Across all ages, 22% of women who had CIN2 or worse were HPV negative. Conversely, 40% of those who were HPV positive did not have CIN. The authors conclude: " younger women with low-grade cytological abnormalities, a single HPV test would not be useful in determining who should be referred for colposcopy or the most effective management at colposcopy. In women over 40, a negative HPV test could be used to rule out further investigation."

HPV self-testing improves coverage and effectiveness in cervical screening

14 March 2010 : PROHTECT (protection by offering HPV testing on cervicovaginal specimens trial) is a cohort study within the setting of the Dutch population based cervical screening programme to assess the feasibility and efficacy of offering cervicovaginal lavage self sampling for high risk HPV testing to women who do not attend the regular screening programme.

Among women who had not responded to a previous screening invitation, self sampling improved compliance and more than doubled the yield of CIN2+ compared with self sampling women who had been screened in the previous round.

More results from Italian NTCC HPV testing trial

04 March 2010 : The latest results from NTCC are reported in the current issue of Lancet Oncology. Briefly, HPV-based screening is more effective than cytology in preventing invasive cervical cancer, by detecting persistent high-grade lesions earlier and providing a longer low-risk period. However, in younger women, HPV screening leads to over-diagnosis of regressive CIN2. The report is accompanied by a freely accessible editorial.

Scotland anticipates significant reduction in invasive cervical cancer

04 March 2010 : 82% of HPV positive cervical cancers in Scotland are caused by HPV types 16 and/or 18. The authors conclude that "A significant reduction in ICC in Scotland should be achieved through the HPV immunisation programme."

Psychological benefits of HPV triage over repeat cytology

24 February 2010 : According to an Australian study reported in this week's BMJ, the use of HPV triage to resolve borderline cervical cytology is better for women’s psychosocial health than repeat smear testing.

Amplification of the human telomerase gene in liquid-based preparations is associated with cervical dysplasia and carcinoma

20 February 2010 : Fluorescence in situ hybridization (FISH) has been successfully applied to liquid-based cytology preparations to analyse the amplification of the human telomerase gene (TERC) in normal and abnormal cervical samples. The results showed a significant association betwen gene expression levels and grade of abnormality, thus providing a potentially useful prognostic marker.

Predicted impact of HPV vaccine on detection of cervical abnormalities in the UK

28 January 2010 : A modelling study has predicted a 63% reduction in invasive cancer, a 51% reduction in CIN3 and a 27% reduction in cytological abnormalities by 2025 in the UK, provided that HPV vaccine uptake reaches 80%. Wales and Scotland can expect earlier benefits in cytological abnormality rates than England, due to the earlier starting age for screening in these countries.

HPV-based screening more effective than cytology in preventing invasive cervical cancer

21 January 2010 : Latest results from the Italian NTCC randomized controlled trial:
Among women aged 35—60 years, one round of HPV screening detects twice as many cases of high grade CIN than cytology. By the second round detection rates are dramatically reduced to about half that of cytology (interpreted as early detection of largely non-regressive disease). Among younger women however, HPV testing detects as much as four times the rate of high grade disease in the first round and just over half that detected by cytology in round two (interpreted as over-detection of regreesive lesions).
Conclusion: HPV primary screening in the over 35s is more effective than cytology in preventing invasive cervical cancer.

Finnish RCT demonstrates superiority of HPV primary screening

07 December 2009 : Results from this latest randomised controlled trial support the use of HPV DNA testing with cytology triage in primary cervical screening for women aged 35 years or older.

Sustained efficacy of Cervarix 6.4 years following vaccination

05 December 2009 : Six-year follow-up results reported in The Lancet show that the bivalent HPV vaccine Cervarix shows sustained efficacy when targeted at young girls before they become sexually active. Vaccine efficacy against incident infection with HPV-16/18 was 95%, and against 12-month persistent infection was 100%. Vaccine efficacy against CIN2+ was 100% for lesions associated with HPV-16/18, and 72% for lesions independent of HPV type.

ARTISTIC results in full

26 November 2009 :
Results in a nutshell
HPV testing and LBC are equally sensitive over two screening rounds, but HPV testing is cheaper, permits a longer screening interval and facilitates large scale automation of primary screening.

Earlier this year (see news item for 21st June 2009) the initial results from the ARTISTIC trial informed us that, over two screening rounds, HPV testing does not add significantly to LBC in terms of the sensitivity of detecting CIN3+. The results of the ARTISTIC trial have now been fully reported by HTA, together with detailed information on the cost-effectiveness and the psychosocial effects of HPV testing.

The HTA report confirms that HPV testing does not add significantly to the effectiveness of LBC, and that the addition of HPV testing to LBC (as a combined test)would not be cost effective. However, HPV testing, used either as a triage for low grade cytological abnormalities, or as an initial screening test triaged by cytology, would be cheaper than cytology without HPV testing. Moreover, HPV testing has the twin advantages of a high negative predictive value, which should allow longer screening intervals, and automated platforms enabling high throughput.The report acknowledges that replacing the current cytology-based programme with HPV primary screening "would require major contraction and reconfiguration of laboratory [cytology] services."

The study confirmed that HPV testing did not appear to cause significant psychosocial distress.

The detailed results can be found in Health Technology Assessment 2009 Vol. 13: No. 51 or by following the link below.

Large RCT shows no benefit of LBC

30 October 2009 : A large randomised controlled trial in the Netherlands indicates that liquid-based cytology does not perform better than conventional Pap tests in terms of relative sensitivity and PPV for detection of cervical cancer precursors.

Cervical screening - from algorithms to risk assessment tools

30 October 2009 : Management decisions for cervical abnormalities are currently based on a combination of cytological, colposcopic, and histological diagnoses. These decision processes are formalised in algorithms that narrow down the clinical management options to a single course of action. As new technologies and new tests come on line the algorithm approach will beome ever more complex and eventually unworkable. A research group in Bethesda is developing a computer-based risk assessment tool that will enable far more accurate and evidence-based clinical decision making in cervical screening programmes of the future.

NHS Cancer Screening Programmes literature database

26 October 2009 : This useful resource of recent research papers covering the NHS breast, cervical, colorectal and prostate cancer management programmes is available at the link below.

HPV is associated with breast cancer

05 September 2009 : A group of Australian researchers have unambiguously demonstrated the presence of high-risk HPV in the cells of breast cancer specimens, thus offering the exciting possibility that at least some breast cancers may be prevented by HPV vaccination.

Short term persistence of HPV is strong predictor of subsequent CIN2+

01 August 2009 : A population based cohort study from Costa Rica has shown that women who test positive for hrHPV at enrolment and after about one year (i.e. positive/positive) have a three year cumulative incidence of CIN2+ significantly higher (17.0%, CI 12.1%-22.0%) than those who tested negative/positive (3.4%, CI 0.1%-6.8%), positive/negative (1.2%, CI 0.2%- 2.5%), and negative/negative (0.5%, CI 0.1%-0.9%).

Cervical screening ineffective in the under 25s

01 August 2009 : This is the conclusion from a large case-control study from the UK, reported in this week''s BMJ.

The authors calculated the odds ratios for developing invasive cervical cancer stage IA or worse (in the next five year interval) in those screened in a given (three year) age band compared with those not screened in that age band (or in two previous years).

Selected results:
Screening age...........Odds ratio for cervical cancer
20-21.............................1.51 ((i.e. no reduction in risk)
22-24.............................1.11 (i.e. no reduction in risk)
30-37.............................0.4-0.57 (i.e. 43%-60% risk reduction)
40-42.............................0.18 (i.e. 82% risk reduction)
62-64.............................0.36 (i.e. 64% risk reduction)

Therefore, screening at ages 20-24 has no detectable impact on cervical cancer rates up to the age of 30.

TOMBOLA results

01 August 2009 : Three separate papers in this week''s BMJ report the long awaited results from the TOMBOLA trial (Trial of the Management of Borderline and Other Low Grade Abnormalities). Collectively the papers reach three main conclusions:

1. Compared with cytological surveillance, a policy of immediate colposcopy for low grade cytological abnormalities detects more cervical intraepithelial neoplasia grade II or worse, and some more grade III or worse, but might lead to overtreatment. Such a policy is associated with a higher rate of reported after effects, which are more severe and of longer duration than those associated with cytological surveillance.
Read the full paper

2. A policy of targeted punch biopsies with subsequent treatment for cervical intraepithelial neoplasia grade II or III and cytological surveillance for grade I or less provides the best balance between benefits and harms for the management of women with low grade abnormal cytology referred for colposcopy. Immediate large loop excision results in overtreatment and more after effects and should not be recommended.
Read the full paper

3. A cost-effectiveness appraisal of three protocols for the management of low grade cytological abnormalities (cytological surveillance, referral to colposcopy for biopsy and recall or referral to colposcopy with immediate treatment based on colposcopic appearance) demonstrated no compelling economic reason to favour any one follow-up method over either of the others.
Read the full paper

PATRICIA HPV vaccine trial final report

09 July 2009 : This week The Lancet reports the final results of the worlds largest trial of a cervical cancer vaccine - PApilloma TRIal against Cancer In young Adults (PATRICIA). The study, involving 18,644 women, confirmed that Cervarix is highly effective at protecting against the two most common cervical cancer-causing HPV types, 16 and 18. The study also showed that the vaccine provides cross-protection against HPV types 31, 33 and 45. and effectively protects against CIN2+ associated with HPV-16/18 and non-vaccine oncogenic HPV types.

HPV testing combined with LBC in primary cervical screening does not improve detection of CIN

21 June 2009 : Results from the ARTISTIC trial have shown that over two screening rounds the addition of HPV testing to liquid based cytology does not improve detection rates of high grade CIN. In the first round of screening HPV testing did result in higher detection rates but by the second round there was an unexpected fall in the number of cases of CIN detected.

HPV vaccine effective in women aged 24-45 not already infected with HPV

02 June 2009 : The quadrivalent HPV vaccine is efficacious in women aged 24—45 years not previously infected with vaccine HPV types. This is the conclusion from a randomised trial reported in the current issue of The Lancet.

Vaccine efficacy against HPV 6, 11, 16, and 18 in the per-protocol group (i.e. women not previously exposed to the relevant HPV types) was 90·5%. In the intention-to-treat population (women who had not been completely vaccinated and/or had pre-existing HPV infection), efficacy was much lower at 30·9%.

Broad spectrum HPV vaccine on the way

31 May 2009 : The May 20th issue of the Journal of the National Cancer Institute reports a study in which mice and rabbits immunized with a multimeric-L2 protein HPV vaccine had robust antibody responses and were protected from infection with HPV16 four months after vaccination.The authors claim that clinical studies in humans are now warranted to assess the safety and immunogenicity of multitype L2 vaccines.

New study supports continued cervical screening beyond age 50

13 May 2009 : A new study in the British Journal of Cancer found that screening continues to identify abnormalities in over-50s, even if the screening tests they had in their 40s came back clear. Lead author Dr Roger Blanks revealed that nearly two thirds of serious pre-cancerous ''CIN 3'' abnormalities currently detected in over-50s would be undetected if screening for this age group was halted.

Age is poor discriminator for deciding when to cease cervical screening

27 April 2009 : In an attempt to answer the age-old question of the age at which it is safe to cease cervical screening, researchers in the Netherlands and Denmark have studied the incidence of cervical cancer following a number of negative smears at different ages.

They gathered information from two age groups: 45-54 and 30-44. All had three straight negative smear tests. Cases of cervical cancer were then recorded during the following ten years.

Throughout the investigation, the levels of screening were comparable in both age groups, and ten years later, the incidence of cervical cancer was similar in both groups. This suggests that the risk of developing cervical cancer is not linked to age, among closely screened women without prior abnormalities.

The data supports the UK cervical screening policy of screening women up to 65 years of age.

Increased long-term mortality in women treated for CIN

24 April 2009 : Women treated for CIN are at an increased risk of subsequent mortality, according to a retrospective cohort study from Finland. Interestingly, women who had delivered post-treatment tended to have decreased overall mortality. However, the mortality rate was significantly increased for women who had subsequent preterm delivery.

Cervarix stable on transient exposure to higher temperatures

22 April 2009 : The HPV vaccine Cervarix, currently being issued in the UK, has been shown to be very stable upon long-term storage at 2-8 degrees, with or without transient exposure to higher temperatures (up to 37 degrees C). This will be welcome news for under-resourced countries where cold storage facilities may be limited.

HPV testing: from India to the world

02 April 2009 : This week''s NEJM reports on a landmark randomized clinical trial from India, involving over 130,000 women. The trial clearly demonstrated that a single HPV test between the age of 30 and 59 dramatically reduced the incidence of, and mortality from, cervical cancer within 8 years. The reduction was far greater than a single conventional cytology test or visual inspection of the cervix with acetic acid (VIA). HPV testing was the most objective and reproducible of all cervical screening tests and was less demanding in terms of training and quality assurance.

The conclusion in an accompanying editorial was straightforward: International experts in cervical-cancer prevention should now adopt HPV testing for widespread implementation.

HPV test of cure: More accurate, less costly

01 March 2009 : A Dutch team has demonstrated that combining hrHPV testing with cytology following treatment for CIN improves clinical outcome and reduces overall costs compared with the current standard of cytology alone.

Management with cytology alone after CIN treatment showed a specificity for detection of residual/recurrent CIN of 80% compared with 91% with cytology plus hrHPV. The sensitivity was 86% with cytology alone and 100% with cytology plus hrHPV.

Total health-care costs were lower with the dual test approach for women at low risk of disease recurrence, because they were safely able to skip the 12-month follow-up visit.

Large cohort study supports HPV primary screening

22 February 2009 : After 5 years of combined cytology and HPV testing in a large general screening population of women aged 30 and older, only 3.99% of cotests had normal cytology and were hrHPV positive. The concerns about excessive HPV positivity among women aged 30 years and older are therefore not borne out.

Post-trachelectomy cytology

14 February 2009 : A report in the current issue of Diagnostic Cytopathology (13th Feb 2009) suggests the use of hrHPV testing for triaging abnormal cytology in post-trachelectomy specimens. Of 9 patients studied, 4 had intermittent or persistent abnormal cytology following trachelectomy. All patients with abnormal cytology went on to have benign biopsies, giving a false abnormal rate of 44%. A strong case for hrHPV testing in these patients then.

Swedescreen HPV trial update

14 January 2009 : This week''s Journal Of the National Cancer Institute carries an article reporting from the intervention arm of SWEDESCREEN - a population-based randomized trial of HPV DNA testing as a cervical screening strategy.

Primary screening with HPV DNA testing followed by cytological triage and repeat screening for persistent HPV infection had a considerably higher sensitivity for detecting high-grade neoplasia. Compared with cytology alone, this strategy resulted in a 34% increase in the sensitivity to detect CIN2+ lesions and a 30% increase in the sensitivity to detect CIN3+ lesions without decreasing the PPVs. This strategy resulted in a only a 12% increase in the number of screening tests, compared with cytology alone.

The researchers conclude that "primary HPV DNA–based screening with cytology triage and repeat HPV DNA testing of cytology-negative women appears to be the most feasible cervical screening strategy."

Evidence for regression of CIN2

23 December 2008 : New evidence from the ALTS trial suggests that 40% of CIN 2 will regress over 2 years, but CIN 2 caused by HPV-16 may be less likely to regress than CIN 2 caused by other high-risk-HPV genotypes.

Psychological barriers to HPV vaccination programmes

22 December 2008 : Currently in the US less than 25 percent of the target population has received an HPV vaccination, far below the target needed to maximize the vaccine’s potential public health benefit.

A study from Yale University reports that parental concerns about increased promiscuity were the single biggest factor in the decision–making process. Financial considerations also influences people’s choices.

“A fundamental but often–neglected aspect of developing and implementing an optimal intervention program is human psychology which influences adherence to recommendations,” said Alison Galvani, Assistant Professor in Epidemiology of Microbial Diseases

Second Carter report acknowledges need for research in NHS

19 December 2008 : Quote from the report of the second phase of the Independent review of NHS Pathology services in England:

"84. In the past one of the strengths of the NHS has been the interrelationship between service provision and research. For example, the use of human biological samples, collected via the pathology laboratory, has been central to the success of much experimental medicine (itself a priority area within health). With a growing focus on service delivery, and in a more cost-conscious culture, there is evidence that the scope for researchers to gain access to such material via the pathology laboratory is becoming more difficult.

85. Such a trend is not in the long-term interests of the NHS – or of patients. We support those who wish to see research embedded into the new ways of working. We welcome the proposal to set up a working group to foster the contribution of pathology services to research. This is an issue that extends beyond pathology but in consolidating pathology services it is essential to build in measures that facilitate translational research."

The endorsement from the Royal College of Pathologists reads:
"The College aims to advance the science and practice of pathology for the benefit of the public to provide public education, to promote research in pathology and to disseminate the results."

Adverse reactions to HPV vaccine rare

09 December 2008 : After more than 380,000 HPV vaccine doses given in Australian schools since 2007, only three schoolgirls were found to have probable hypersensitivity to the quadrivalent vaccine, Gardasil. Read the full paper for free in this week''s BMJ.

Cancer Incidence by Deprivation, England, 1995-2004

05 December 2008 : A fascinating insight into the link between social deprivation and cancer in England:
"Overall it is estimated that if the entire population had the incidence rates of the least deprived quintile, there would be approximately 14,300 fewer cancers each year". David Forman, Information and Analysis Lead, NCIN.

Social deprivation doubles the risk of cervical cancer

Modelling research shows Cervarix-induced Immunity may last for over 20 years

04 December 2008 : Results of three statistical models presented at the European Research Organisation on Genital Infection and Neoplasia (EUROGIN) annual meeting suggest that women vaccinated with the HPV vaccine Cervarix could look forward to a prolonged immune response against hpv 16 and 18 for at least 20 years.

HPV prevalence in South Wales

29 November 2008 : HPV prevalence data are needed for two reasons: assessment of the impact of prophylactic HPV vaccination and to help inform future screening strategies. This research provides such data for the South Wales area. Curiously, HPV type 31 is more common than type 18 in this part of the world.

Oral cytology revisited

14 November 2008 : Cytologists have long pondered the potential use of cytology for the early diagnosis of oral cancer. However, oral cytology has always suffered from poor sensitivity and specificity, largely because of the difficulty in obtained adequate specimens. Interest has recently been revived due to the introduction of a cytobrush for cell collection as well as a computer-assisted analysis (Oral CDx®). as described in this review paper in the Journal of Oral Pathology & Medicine.

Molecules meet morphology in lung cancer detection

27 October 2008 : Automated detection of genetic abnormalities combined with sputum cytology is a sensitive predictor of lung cancer, according to a study reported in the journal Modern Pathology.

A combination of cytological atypia and genetic abnormalities for 3p22.1 and 10q22.3 (detected by fluorescence in situ hybridisation) achieved 74% sensitivity and 82% specificity, compared with only 37% sensitivity and 87% specificity when cytology alone was used.

New imaging technique detects early cervical cancer

26 October 2008 : A pilot study reported in the journal Radiology has shown that a new imaging technology (diffusion-weighted magnetic resonance imaging) can identify small cervical tumours, reducing the need for radical surgery in Stage Ia and Ib1 Disease.

Long term predictive values of cytology and HPV testing in cervical cancer screening

26 October 2008 : Combining cytology with HPV testing improves the sensitivity of screening, but how often does it need to be repeated? A European study in the BMJ suggests that 6 years is probably a safe interval, and that HPV testing alone may suffice. Among ~25,000 women tested in 6 countries, the rate of CIN3+ at 6 years was only 0.27% in those who were HPV-negative at baseline compared with 0.97% in those who were cytology-negative. Combining the two tests made little difference.

Study to determine the minimum cellularity required for the reliable assessment of Liquid Based Cervical (LBC) cytology samples

17 October 2008 : The number of cells required for LBC samples to be deemed adequate remains the subject of debate. There is a risk that samples may be described as negative when they are really inadequate and that abnormalities could therefore be missed.

An adequate LBC sample is one in which sufficient numbers of cells are present to allow the detection of an abnormality were it to be present. This study aims to establish the threshold of cellularity which will minimise the risk of false negative reports.

HPV testing with p16 triage could be the way forward

07 October 2008 : That''s the conclusion from a substudy of the NTCC HPV screening trial in this week''s The Lancet Oncology.

It is accepted that HPV testing lacks the specificity of cytology, leading some to suggest that HPV screening and cytology triage provides the best combination of sensitivity and specificity for cervical screening.

This study puts the cat among the pigeons by suggesting that p16 triage following a positive test for high risk HPV might be the best combination, apparently leaving no place for cytology.