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LRCTC News - 2014

Urine-based HPV test 'feasible alternative for cervical cancer screening'
25 September 2014

A new study published in The BMJ claims that a simple urine test for human papillomavirus could increase screening uptake among women by offering them a non-invasive option.

According to the researchers of this latest study - including Dr. Neha Pathak of the Women's Health Research Unit at the Blizard Institute of Barts and the London School of Medicine and Dentistry in the UK - past studies have indicated that an alternative to Pap testing could be to test urine for signs of HPV. But they note the accuracy of such testing has been unclear. Dr. Pathak and colleagues set out to compare the accuracy of urine HPV testing against the collection of cervical samples.They have analyzed the results of 14 studies that looked at both forms of testing, involving a total of 1,443 women who were sexually active.They found that on average, the sensitivity of urine HPV testing - the proportion of positive results correctly identified - was 87%, while specificity - the proportion of negative results correctly identified - stood at 94%, compared with collection of cervical samples. When using urine HPV testing to identify HPV types 16 and 18 - the primary causes of cervical cancer - sensitivity was 73% and specificity was 98%.Accuracy of the urine HPV test increased when the first urine sample of the day, referred to as the "first-void," was used.

They note, however, that their results should be "interpreted with caution" because of the variation found between individual studies, which could lead to overestimation or underestimation of results.

"The consequences of overestimation are especially important as they can lead to unacceptable morbidity and mortality," say the researchers. "False negative results would lead to missing cases of precancerous or cancerous lesions, and false positive results would lead to overinvestigation and anxiety Both scenarios could easily result in a lack of trust in HPV testing."

The team believes more studies are warranted to further investigate the accuracy on urine HPV testing, and to look at the feasibility and costs of this method in a clinical setting.

In an editorial linked to the study, Harry C. Kitchener and Gemma L. Owens, of the University of Manchester in the UK, say urine HPV testing could be an achievable and beneficial alternative to HPV testing of cervical samples.

"In well-resourced health systems, self-sampling could be used for women who are reluctant to attend for regular cervical screening," they note. "In lower income countries that lack infrastructure, self-sampling might even be beneficial and cost-effective for all women who are eligible for screening. More research is now required to identify the true clinical performance and acceptability of urine testing for HPV in both settings."


Accuracy of urinary human papillomavirus testing for presence of cervical HPV: systematic review and meta-analysis Neha Pathak et al., published in The BMJ, 16 September 2014.

Editorial: Urine testing for HPV, Harry C. Kitchener, Gemma L. Owens, published in The BMJ, 16 September 2014

Finding better ways to treat, prevent HPV
12 September 2014

Gathering of the brightest minds to discuss new advances in HPV research – and what’s still needed

Twenty-nine years ago, scientists didn’t know what caused many of the genital-tract cancers they studied, much less how to stop them.

Today, not only has human papillomavirus been pinpointed as  the viral perpetrator behind nearly all genital-tract and some head and neck cancers, there’s now an incredibly effective vaccine that can prevent high-risk HPV infections from ever developing into cancer.

“You can almost say on the street, ‘I’m doing HPV research’ and ordinary people will know what that is,” said Aaro Turunen, an HPV researcher from the University of Turku in Finland.  “It’s a sexy subject, especially for the media.”

While scientific advancements, public awareness and yes, media coverage, have grown exponentially in the last three decades, there is still much to learn and do – particularly with regard to getting the vaccine to the people who most need it, both here in the U.S. and around the world.

That’s where the International Papillomavirus Conference, currently in its twenty-ninth year, comes in.

The HPV2014 conference, now underway at the Washington State Convention Center in Seattle, has drawn the brightest minds in HPV research, including nearly 1,300 basic scientists, public health researchers, physicians, providers and others dedicated to eliminating the suffering caused by the human papillomavirus. The goal of the conference is to share cutting-edge scientific advances in the field of HPV infection and disease and come up with new ways to collaborate to advance science and public health.

The conference officially began today but kicked off early Wednesday with two days of clinical and public health pre-conference workshops covering everything from HPV infection and disease in HIV-infected men to implementing and evaluating two-dose vaccine schedules to a peek at the next generation of HPV vaccines coming down the pike.

Conference chair Dr. Denise Galloway, who holds a joint appointment with Fred Hutch’s Human Biology and Public Health Sciences divisions, said she was thrilled the conference was taking place in the Hutch’s back yard.

“I’m excited that the HPV meeting will be here as it recognizes the strength and breadth we have in HPV research in Seattle,” she said. “Our main goal was to provide a setting where people from all over the world who study various aspects of papillomavirus biology, disease and prevention could come together to share their data and ideas.”

Galloway, who has been investigating the link between cancer and viruses since 1978, was instrumental in both discovering HPV’s association with many cancers and paving the way for a vaccine able to check cervical cancer before it starts in hundreds of thousands of women worldwide.

These days, she’s researching B cell memory in order to determine how effective the HPV vaccine is over a person’s lifetime.

“If a vaccine is going to work, it’s not just important how well this will stimulate the immune system, which you can measure within a couple of months after you get the vaccine,” she said. “You also want to know, is it going to be durable? Are you going to have a response 10 years, 20 years or 30 years from now? We’re trying to figure that out by looking at the cells that are there and available to make the responses in 10 and 15 years.”

Long-term efficacy is just one of many topics covered at the conference, which boasts an ambitious lineup of over 700 abstract presentations, nine satellite sessions, four symposia and four plenary sessions, all highlighting basic, clinical and public health science topics ranging from molecular virology to novel cancer screening and treatment strategies to global public health.

Also represented at the conference are pharmaceutical companies such as Merck, producer of the HPV vaccine Gardasil, and Roche, developer of the cobas HPV test. Also present are medical device manufacturers such as QIAGEN, which along with support from Seattle’s PATH, developed the careHPV test, a field-friendly and inexpensive test that allows women, particularly in developing countries, to gather screening samples themselves.

On Friday morning, Dr. Freddie Bray of the International Agency for Research on Cancer talked about the need for quality data and cancer registries, especially in developing countries and and Dr. Scott Ramsey of Fred Hutch’s HICOR division spoke about the value of prevention-based studies and interventions.

“There was a nice study done by the CDC a few years ago that looked at the cost effectiveness of HPV vaccination of young girls in the U.S.,” he said. “This is a slide I wish I could produce as a health economist more often. HPV vaccines in this population are among the most cost effective interventions we have in the U.S.“

Despite the efficacy and overall cost effectiveness of the vaccine, however, delivery and implementation of the vaccine remain a problem, said Galloway.

“We need to find better strategies to get girls and boys to take the vaccine,” she said. “In other countries, where they have school-based programs, they’re doing much better than in the U.S.”

Saturday’s plenary will feature talks on the natural history of HPV infection and cervical cancer, the natural history of oral HPV and its progression of oropharyngeal cancer and the “genetic arms race” between host and viral genomes, presented by Fred Hutch’s Dr. Harmit Malik. Vaccines will be covered in the Sunday plenary session with talks on Merkel cell carcinoma by Fred Hutch’s Dr. Paul Nghiem, an update on Australia’s HPV vaccination program and a presentation on vaccine dosage.

“There is a growing consensus of switching from three doses to two and it will be exciting to hear more about that,” said Galloway.

Finnish researcher Turunen, whose research focuses on the relationship between HPV and the Epstein-Barr virus, said he was amazed at how much the field – and the International Papillomavirus Conference -- had grown, adding that a much smaller HPV conference took place in Seattle 20 years ago.

Ref Fred Hutch Research Centre News 22.8.14

“Both HPV researchers were there,” he quipped.

Startup’s antiviral drug combats HPV, new study shows
12 September 2014

San Diego startup Hera Therapeutics is developing a topical antiviral drug that attacks human papillomavirus -

The drug candidate, HTI-1968, blocked the replication of HPV-16, HPV-18 and HPV-11 cells, according to the NIAID-sponsored study. The work was conducted primarily by University of Alabama researchers Louise T. Chow and Thomas Broker. The drug could be effective against more, CEO Karl Hostetler said, but these are the only three HPV strains available for screening through the NIH.

“We believe it’s possible the drug’s pangenotypic – that is, active against all strains – but can’t prove that because these are the only three strains available right now for testing,” Hostetler said.

Hera Therapeutics doesn’t yet know the exact steps the antiviral takes, but it essentially blocks the pathway that allows the virus to make its DNA using cellular enzymes, Hostetler said.


“It’s a nucleoside analog, and that’s all we’re wiling to say about it right now,” Hostetler said.

The nascent company has started safety testing for the drug, and hopes to file an IND by late next year. It is working with a contractor to develop a prototype to combat the sexually transmitted infection, Hostetler said.

Hostetler, a professor emeritus at University of California, San Diego, previously founded three other companies - Vical, Chimerix and Triangle Pharmaceuticals. He founded Hera Therapeutics in late 2012. It has received $2.4 million in funding to date, including $1.3 million last month.The startup is housed in the Janssen Labs accelerator in San Diego.

HPV is painfully common, with 6.2 million Americans getting newly infected each year, according to the CDC. Nearly 4,000 women die each year from invasive cervical cancer, which is largely a result of an undetected case of the virus. However, outside of the Gardasil vaccinethat’s not really available to women older than 26, or those who have already contracted it, there isn’t much in the way of HPV prevention or treatment. Hostetler expounds on why there’s been a dearth of HPV antivirals on the market:

“Over the years, there haven’t really been many antiviral drugs developed for HPV, probably because the screening process is so difficult.

Most antivirals interfere with the viral polymerase that makes the DNA or RNA. The thing about HPV is that if it does not have its own polymerase enzyme, it hijacks some of the human cell DNA synthesizing pathways to make it viral DNA, and that’s led a lot of people to believe that you couldn’t develop a nucleoside that would be selective for the virus.

HIV, for instance, has a retroviral polymerase, and AZT and tenofivir and lots of other drugs inhibit that. That’s great. But here’s a virus that doesn’t have a polymerase, so it’s been very difficult historically to find things that will selectively block it.”

However, a number of immunotherapy candidates are in clinical testing to treat HPV, so it’ll be worth watching to see which therapies shake out as medically – and commercially – viable

Ref Medcity News by Meghana Keshavan  August 25, 2014


Small study: Text message-based cancer screening education may help at-risk minority groups
12 September 2014

In a recent JMIR study, a team of researchers in Minnesota explored the potential of mobile health to reach people who sometimes fall through the cracks of the healthcare system.

They found that a text message intervention could help Korean American women, a group that has one of the highest cervical cancer mortality rates in the United States, seek preventative screenings (Pap tests).

“A variety of structural and cultural factors act as barriers to screening for Korean American women,” the authors write. “Structural obstacles include health access due to inadequate health insurance, expense, time constraints, and language limitations. Cultural barriers to cervical cancer screening encompass lack of knowledge regarding cervical cancer and cervical cancer screening, a wrongly held belief that screening is unnecessary in the absence of symptoms or at young ages, cultural modesty or embarrassment, lack of culturally appropriate health care providers, and fear of receiving negative screening results.”

Researchers designed a text message based intervention for a study group of 30 Korean American women, 90 percent of whom had been living in the United States for less than 9 years and nearly two-thirds of whom had a family history of cancer. Based on a screening conducted ahead of time, women received messages tailored to their specific needs; for instance, a woman who had scored high on a pre-test scale for cultural embarrassment might receive the message “We understand it is a bit embarrassing to get it done. But do it for you! Your happy cervix will appreciate it!” in addition to the other messaging. Participants received messages for seven days, and many of them were interactive, prompting responses from the participants.

Results were mixed. A week after the intervention, participants were generally more knowledgable about cervical cancer and the importance of screening. Significant differences were observed in general knowledge, knowledge of risk factors, and knowledge about and attitudes toward the Pap test. But when asked whether they planned to get a screening in 1 year, 3 months, 1 month, or not at all, the increase wasn’t statistically significant, though this could be owing partly to the small sample size. At a three month follow-up, just seven of the 30 women had actually gone in to get screened for cervical cancer.

Nonetheless, researchers are hoping to follow up the study with a larger RCT, possibly modifying the experiment design to deliver the messages over a shorter time or to incorporate a smartphone app.

“Given the widespread use of mobile phones (98 percent) and smartphones (83 percent) among young adults, a mobile phone-based health intervention could be a cost-effective method of reaching hard-to-reach populations with tailored, individual messages that cover broad content areas and overcome restrictions to place and time of delivery,” they wrote. “Our developed model could be expanded for delivery to different age groups of Korean American women to promote additional types of cancer screening, such as colonoscopy or mammogram. It could also be used with other underserved minority groups. Vietnamese, Hmong, and Laotian American women face similar barriers to cancer screening and report high cervical cancer incidence and mortality. It is likely that these populations may also benefit from a similarly tailored intervention approach.”

Ref: MobiHealth News By: Jonah Comstock  Aug 28, 2014


HPV vaccination programme schedule changing from 3 to 2 doses
16 May 2014

Change follows on from advice from the Joint Committee on Vaccination and Immunisation (JCVI).

A letter from Public Health England, the Department of Health and NHS England was disseminated today detailing changes to the human papillomavirus (HPV) vaccination programme. From September 2014, the schedule will change from 3 to 2 doses. The HPV vaccine is currently routinely offered to girls aged 12 to 13 in school year 8.

This follows a recommendation from the Joint Committee on Vaccination and Immunisation (JCVI) this March. Recent research shows that antibody response to the 2 dose schedule in adolescent girls is equivalent to the response that correlated with protection against persistent infection and precancerous lesions in the initial vaccine trials. Both Gardasil and Cervarix have been approved for use in a 2 dose schedule.

Since 2008, the first year of the routine vaccination programme for 12 to 13 year old girls, acceptance of the vaccine has been consistently high. In the school year starting September 2012, 89.6% of girls received at least 2 doses of vaccine, and 86.1% completed the 3 dose course. Recent data indicate that the HPV vaccination programme has successfully reduced vaccine-type HPV infections in sexually active young women in England[1]. It is hoped the new dosage schedule will build upon this success.

Unlike the current schedule, the 2 doses of the new schedule must be given at least 6 months and not more than 24 months apart. Consult the complete letter for detailed guidance on the recommended gaps between the 2 doses.

Importantly, girls who have received 2 HPV vaccine doses under the 2013 to 2014 programme should still receive their third dose, to complete their course. An updated Q & A for health professionals and revised information leaflet will be available from mid-June.

For further information, please read the full letter outlining programme changes


  1. Mesher D, Soldan K, Howell-Jones R, Panwar K, Manyenga P, Jit M, Beddows S, Gill ON. Reduction in HPV 16/18 prevalence in sexually active young women following the introduction of HPV immunisation in England. Vaccine 2013; 32(1):26-32.

DNA or Pap?
17 April 2014

Some women's health advocacy groups are pushing the US Food and Drug Administration to not approve Roche's cobas HPV test to replace the Pap test as a first-line choice for cervical cancer screening, the AP reports.

FDA is considering making the move, as its Microbiology Devices Panel of the Medical Devices Advisory Committee just last month recommended using the cobas, which tests for HPV DNA, as a first-line option for assessing cervical cancer risk in women 25 years and older.

Groups like the American Medical Women's Association and Our Bodies Ourselves say that moving away from the well-tested Pap test would be "a radical shift" that could lead to higher medical costs, over treatment, and confusion.

"It replaces a safe and effective well-established screening tool and regimen that has prevented cervical cancer successfully in the US with a new tool and regimen not proven to work in a large US population," the groups say in a letter to FDA commissioner Margaret Hamburg.

They worry that the DNA test will lead to overtreatment of younger women who carry the HPV virus, but who have little risk of developing cervical cancer. They also say the test is not very useful by itself because "so many women have HPV that will disappear without any treatment," Diane Zuckerman of the Cancer Prevention and Treatment Fund tells the AP.

"Having an HPV test without also getting a Pap smear to check for problems is going to scare a lot of women who are not developing cervical cancer," she adds.

Although Pap testing has contributed significantly to a 50 percent decrease in cervical cancer in the US over the past 30 years, an estimated 12,000 cases of the cancer are expected to be diagnosed this year. The latest guidelines from the American Cancer Society recommend a Pap and HPV test every five years or a Pap alone every three years in women over the age of 30, but it does not recommend the HPV test in women under 30 because it would increase the odds of more invasive testing that can be harmful to the cervix and could affect pregnancies.

Roche wants FDA to clear the company to market its test to women ages 25 and up, and the FDA's microbiology devices panel recommended unanimously that the cobas test is safe and effective as a first-line screening tool.

But the cost is a concern, AP reports. The HPV test costs between $80 and $100, more than twice the $40 Pap, and Roche has proposed that women who test positive for HPV be referred for colposcopy, which can cost up to $500.


Genomeweb The Daily Scan April 16 2014 by Jian Sun

FDA Panel: Roche's DNA Test Can Replace Pap Smear
18 March 2014

An FDA advisory committee voted unanimously Wednesday to recommend that the Pap smear be replaced with a human papillomavirus (HPV) test as the first-line standard of care for cancer screening.

The FDA's Medical Devices Advisory Committee Microbiology Panel agreed by a vote of 13-0 in each of three successive votes that the cobas viral DNA test for HPV -- made by Roche Molecular Systems -- was safe and effective for cervical cancer screening, and that the benefits of the tests outweighed the risks.

The cobas test currently has approval as a follow-up assessment for women 21 and older who have abnormal Pap tests, and as a co-test with the Pap smear to screen for the high-risk p16 and p18 HPV strains in women 30 to 65. The test comprises genotyping for HPV16 and 18 and pooled assessment of 12 additional high-risk HPV strains.

According to the proposal submitted by Roche, women 25 and older who test positive for HPV16 or 18 would proceed directly to colposcopy for further assessment.

Patients who test negative for HPV16 or 18 but positive for the other high-risk strains would have a Pap test to determine the need for colposcopy. Women who have a completely negative test would be followed at their physician's discretion.

Panelists did express some concerns about dropping the age at which women should have the test from 30 to 25. The ATHENA study used as the basis for the application found that about 11% of women ages 25 to 29 tested positive for HPV16 or 18 with the cobas test, compared with 7.28% among women 25 to 29 who had cytology alone as their first-line screening. Panel member Paula Hillard, MD of Stanford University in California, said that would mean more patients in that age group "who will be anxious about potentially having cancer."

In addition, Hillard expressed concern about off-label use. "I'm concerned that all those women potentially with other high-risk positivity won't go to Paps next but go [straight] to colposcopy. That's not what's proposed here, but what control does FDA have once it's out there?"

Panelist Kenneth Noller, MD of the American Board of Obstetrics and Gynecology, in Dallas, agreed that real-world use could differ from the protocol proposed by Roche. "I've been watching how people practice; if you're high-risk HPV positive you're going to get colposcopy," he said. "That doesn't necessarily mean it's bad -- it's what you do with the colposcopy."

Noller added that although he was "somewhat biased against dropping the age to 25 before I came here ... I find the data presented today somewhat compelling to drop it to 25."

Panel member Kimberly Hanson, MD, MHS of the University of Utah and ARUP Laboratories, both in Salt Lake City, agreed. "Now we have the opportunity to identify women earlier, and to me that's compelling," she said. "Although colposcopy is invasive and can be anxiety-provoking, it's really very safe, so I think I'm leaning toward earlier screening."

The committee members were not concerned about losing other diagnostic benefits of the Pap smear -- such as finding trichomonas and abnormal endometrial cells -- that would be lost if Pap smears were no longer the first-line screening method. "If this is how you're diagnosing trichomonas and [other diseases], there are much more effective ways of doing it," said panel chair Angela Caliendo, MD, PhD, of Rhode Island Hospital in Providence.

The presentations by FDA staff and Roche relied on long-term follow-up data from ATHENA, a 47,208-patient cohort study that was conducted in the U.S.

According to the summary submitted by FDA staff members, "The data show that the proposed primary screening indication for the cobas HPV test detects more women with disease and requires fewer women without disease to go to colposcopy than cytology alone."

The staff summary included the following performance characteristics of the cobas test versus cytology in the prospective cohort study:

By Joyce Frieden News Editor, MedPage Today  12.3.14


  • Sensitivity for ≥cervical intraepithelial neoplasia (CIN3) -58.26% versus 42.63%
  • Positive predictive value -12.25% versus 6.47%
  • Negative predictive value -0.42% versus 0.59%
  • False-positive rate -4.09% versus 6.04%


Benefit-risk analyses favored the HPV DNA test whether expressed in terms of number of cases of high-grade cervical disease per 10,000 women screened or per 100 colposcopy procedures.

The FDA is not bound to follow its advisory committees' recommendations, but does so in most cases.

A Power Surge for Cancer Immunotherapy
12 February 2014

Antibodies,vaccines,and engineered T cells fuel new optimism

The field of cancer immunotherapy,which explores how a patient's own immune system can be coaxed into fighting tumours is suddenly booming.The pharmaceutical industry is investing heavily in a braod range of strategies.

Many tumours are inherently resistant to the body's immune response.Because they develop from our own cells,they usually do not contain anything that the immune system would recognise as foreign and thus view as a potental threat.Researchers believe that many cancers can dodge our defences by exploiting regulatory pathways that the immune system normally uses to prevent overactivity and autoimmunity.

However many researchers are now unveiling multiple strategies to kee the immune system active ,identifying and targeting cancers as threats , and then eliminating them.Dr Butterfield the Professor of Medicine,Surgery and immunology at the University of Pittsburgh Cancer Institute Immunlogic Monitoring and Cellular Products Laboratory syas " the punchline of the lecture is no longer limited to "my therapy was safe and well-tolerated by the patient".Now you hear "This is the high percantage of overall clinical responses of patient's tumours melting away,and these are the breadth of tumour types that repsonded ,and the duration of patient's surviving" she says.

Releasing the Blockades

So far, a theurapeutic intervention that relies on T-cell checkpoint inhibitors or bockades has captured much of the early excitement.When repsnding to infections, the immune system normally tamps down its own activity after it has cleared the pathogen.This response ,prompted by inhibitory signals,can be mediated by suppressor cells and by surface molecules on T-cells themselves."we try to release those blockades, get rid of the suppressor cells,remove these checkpoints where the T-cells tell themsleves ,'I have been for a while I should turn myself off ' Dr Butterfield says.

In 2011 , the US FDA approved a monoclonal antibody ipilimumab for the treatment of metastatic melanoma. One of the first immunotherapy drugs on the market,ipilimumab allows T-cells to remain active by blocking an inhibitory signal emitted by a surface protein called cytotoxic T-lymphocyte antigen 4 (CTLA-4).Although the drug's overal repsonse rate of approximately 11% is relatively modest, the response in many patients has been durable. This success comes with a caveat ,however by ramping up T-cell activity,checkpoint inhibitors can cause autoimmune-based side effects.As the immune therapies move forward in clinical trials, researchers conceded that a major challenge will be boosting an antitumour T-cell repsonse while minimising autoimmunity.

The next generation strategy,researchers are designing monoclonal antibodies that bind to proteins in a similar signalling pathway named programmed death 1 (PD-1).Whereas  the PD-1 protein appears on the outer surface of T-cells, a binding partner called prommed death ligand (PDL-1) studs the surface of tumour cells.When the T-cells arrive at the tumour site,crosstalk between the two proteins  instructs the T-cells to shut down.More than six companies are now developing antibodies against either PD-1 or PDL-1, to block these T-cells inactivating signals.

In phase 1 clinical trials the best response rate has been closer to 30%, with less toxicity than ipilimumb.

With the growing body of molecular and cellular knowledge researchers can start to take more precisely targeted and personilased approaches to induce effective tumour immunity.


 by Bryn  Nelson editorial CytoSource in the  Cancer Cytopathology Journal January 2014 Vol 122 Issue 1



Precancerous Cells on Cervix Tied to Higher Risk of Disease, Death
22 January 2014

Women who have been diagnosed with and treated for precancerous cells on the cervix may be at increased risk for developing and dying from cervical or vaginal cancer, new research suggests.

The study authors analyzed data from more than 150,000 Swedish women who were treated for abnormal cells on the cervix. Of those, nearly 1,100 were later diagnosed with invasive cervical cancer and about 150 were diagnosed with invasive vaginal cancer. There were more than 300 deaths from cervical cancer and about 50 deaths from vaginal cancer.

As women who had been treated for precancerous cells on the cervix grew older, their risk of cervical or vaginal cancer increased. The risk accelerated after age 60 and again after age 75, according to the study. The researchers found that incidence rates of cervical and vaginal cancer in the oldest group of women exceeded 100 per 100,000 women.


The more recently women had been treated for abnormal cells on the cervix -- and the older they were at the time of treatment -- the greater their risk of cancer. Those who were treated at ages 60 to 69 had a five times higher risk than those treated at ages 30 to 39, according to the study.

The findings were published online Jan. 14 in the journal BMJ.

The risk of death from cervical or vaginal cancer also increased with age among women who had been treated for abnormal cells on the cervix, according to a journal news release. Thirty years after treatment, these women were more than twice as likely to die from cervical or vaginal cancer than those in the general population. At age 72, death rates from these cancers increased to 50 per 100,000 women, the study found.

The older a woman was when she was treated for precancerous cells on the cervix, the greater her risk of death from cervical or vaginal cancer, according to the news release.

The findings show that women who have been treated for abnormal cells on the cervix "should be followed up in old age," said researcher Bjorn Strander, from the University of Gothenburg, and colleagues at the Karolinska Institute, both in Sweden.

It is worrying that the study found that women who received treatment more recently were at greater risk of developing cervical and vaginal cancer, Dr. Marc Arbyn, from the unit of cancer epidemiology of the Scientific Institute of Public Health, in Brussels, Belgium, said in an accompanying editorial.

Arbyn called for research to identify signs that predict a woman's future risk of cervical and vaginal cancer.

"Measures should be taken to assure full compliance with follow-up after treatment of cervical pre-cancer,"


SOURCE:, news release, Jan. 14, 2014




Cervical Cancer Screening Tests in Older Women
22 January 2014

Researchers say their results support screening women up to age 65 and beyond

Cervical cancer screening beyond age 50 saves lives and remains beneficial to women up to age 69, a new British study suggests.

Both the U.S. Centers for Disease Control and Prevention and the U.S. Preventive Services Task Force recommend that cervical cancer screening end at age 65.

In this new study, researchers examined data from all 1,341 women aged 65 to 83 in England and Wales who were diagnosed with cervical cancer between 2007 and 2012, and compared them to women in the same age group who did not have cervical cancer.

The results showed that women who did not undergo cervical cancer screening after age 50 were six times more likely to be diagnosed with cervical cancer than those who had regular screenings between ages 50 to 64 and had no abnormalities. There were 49 cancers in the first group versus eight cancers in the second group per 10,000 women over 20 years, found the study in the journal PLoS Medicine

Continue reading below...

The rate of cervical cancer was 86 per 10,000 over 20 years among women who were screened regularly between ages 50 to 64 and found to have abnormalities, according to a journal new release.

The findings suggest that cervical cancer screening in older women has a substantial impact in reducing cervical cancer risk, said researchers Peter Sasieni and colleagues from Queen Mary University of London.

"Screening up to age 65 years greatly reduces the risk of cervical cancer in the following decade, but the protection weakens with time and is substantially less 15 years after the last screen. In the light of increasing life expectancy, it would seem inappropriate for countries that currently stop screening between the ages 60 and 69 years to consider reducing the age at which screening ceases," the researchers concluded.

This type of new data from older women can help experts determine whether current guidelines that recommend a halt to cervical cancer screening at age 65 meet all women's needs, Anne Rositch, from the University of Maryland School of Medicine, and colleagues wrote in an accompanying editorial.

Here are the cervical cancer screening guidelines from the U.S. Centers for Disease Control and Prevention:

  • Start getting regular Pap tests at age 21. The Pap test is one of the most reliable and effective cervical cancer screening tests. If your Pap test results are normal, your doctor may tell you that you can wait three years until your next Pap test.
  • If you are 30 years old or older, you may want to have a human papillomavirus (HPV) test along with the Pap test. Both tests can be performed by your doctor at the same time. If your test results are normal, your chance of getting cervical cancer in the next few years is very low. Your doctor may then tell you that you can wait as long as five years for your next screening. But you should still go to the doctor regularly for a checkup.
  • If you are 21 to 65 years old, it is important for you to continue getting a Pap test as directed by your doctor, even if you think you are too old to have a child or are not having sex anymore. If you are older than 65 and have had normal Pap test results for several years, or if you have had your cervix removed as part of a total hysterectomy for non-cancerous conditions, like fibroids, your doctor may tell you that you do not need to have a Pap test anymore.

Here are the cervical cancer screening guidelines from the U.S. Preventive Services Task Force:

  • Women aged 21 to 65 years should have a Pap test every three years. Women aged 30 to 65 who want to lengthen the screening interval can undergo screening with a combination of Pap and HPV testing every five years.
  • Screening is not recommended for women younger than 21, or for women older that 65 "who have had adequate prior screening and are not otherwise at high risk for cervical cancer."
  • Screening is not recommended for women who have had a hysterectomy with removal of the cervix and who do not have a history of a high-grade precancerous lesion or cervical cancer.
  • HPV testing, alone or in combination with a Pap test, should not be used for cervical cancer screening in women younger than 30.


PLoS Medicine, news release, Jan. 14, 2014

HPV Vaccine: The Earlier, the Better
08 January 2014

Women who were 18 and up or had abnormal cervical cytology when vaccinated against human papillomavirus (HPV) subsequently had rates of cervical dysplasia similar to those of unvaccinated women

Women ≥18 without cervical abnormalities at vaccination had a 23% reduction in the risk of high-grade squamous intraepithelial lesions (HSIL) as compared with unvaccinated women. The quadrivalent vaccine did not appear to protect against HSIL among women who had abnormal cytology at the time they were vaccinated, they reported online in the Journal of Clinical Oncology.

"A significant percentage of vaccinated women may not be protected against HSIL or lesser dysplasia especially if they were vaccinated at older age or had abnormal cytology before vaccination," Salaheddin M. Mahmud,MD, PhD, of the University of Manitoba in Winnipeg, and colleagues concluded.

"These findings affirm the importance of vaccination before any significant exposure to HPV occurs and underscore the need for screening programs that cover all sexually active women, even if they were vaccinated," they wrote.

The quadrivalent HPV vaccine has been shown to reduce the risk of cervical cancer, which evolves from infection with HPV 16 and 18 in 70% of cases worldwide. Whether the vaccine protects against cervical dysplasia had been been studied by use of population-based individual-level data, the authors noted in their introduction.

To examine HPV vaccine effectiveness against cervical dysplasia, Mahmud and colleagues reviewed records for 3,541 females vaccinated at age ≥15 in Manitoba from September 2006 to April 2010. Each vaccinated patient was matched with three unvaccinated patients.

Investigators calculated hazard ratios for three outcomes: atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesions (LSIL), and HSIL.

During a median follow-up of 3.1 years, vaccinated patients had LSIL and HSIL rates of 3.3% and 2.3%, respectively, compared with 3.7% and 2.6% for unvaccinated patients. No patient (vaccinated or not) developed cervical cancer during follow-up, but 12 vaccinated patients (0.3%) and 22 unvaccinated patients (0.2%) developed carcinoma in situ.

Investigators analyzed the data by age group and history of abnormal cervical cytology. Vaccine effectiveness varied by both factors.

Among girls ages 15 to 17 at enrollment, vaccine effectiveness estimates were 35% against HSIL, 21% for LSIL, and -1% for ASCUS. Exclusion of girls who did not have at least one Pap test after enrollment resulted in higher estimated effectiveness: 46% against HSIL, 35% against LSIL, and 23% for ASCUS.

For patients who were ≥18 and had no history of abnormal cytology before enrollment, estimated effectiveness rates were 23% of HSIL, -18% for LSIL, and -20% for ASCUS. A history of abnormal cytology reduced the estimates to -8% for HSIL, 37% for LSIL, and 56% for ASCUS but with wide confidence intervals.

Exclusion of women ≥18 who did not have at least one Pap test after enrollment resulted in estimated vaccine effectiveness rates of 35% for HSIL, 2% for LSIL, and -5% for ASCUS in the subgroup who had no history of abnormal cytology before enrollment and rates of -33%, 25%, and 53% for those with a history of abnormal cervical cytology.

"Postmarketing epidemiological studies are needed to evaluate the real-life effectiveness of the HPV vaccines and to monitor their impact on other preventive measures such as screening and sexually transmitted infection control programs," the authors concluded.

The findings confirm data from previous studies showing that HPV vaccine is less effective in older teens and young women, said Ronald Alvarez, MD, PhD, of the University of Alabama at Birmingham.

"We know that this group of women is more likely to have had exposure to human papillomavirus and perhaps even had some disease," Alvarez told MedPage Today. "In that setting, we know that the HPV vaccine is less likely to be effective."

HPV vaccine will be most effective when three criteria are met, said Krishnansu Tewari, MD, of the University of California Irvine.

  • No high-risk vaccine-specific HPV DNA on the cervix at the time of vaccination
  • No antibodies against the high-risk vaccine-specific HPVs in the serum of the patient at the time of vaccination
  • The patient’s cervical cytology is, and has been normal at the time of vaccination

“It is so important that males and females are vaccinated as early as possible, before the so-called sexual debut -- before they start having sex,”

Primary source: Journal of Clinical Oncology
Source reference: Mahmud SH, et al "Effectiveness of the quadrivalent human papillomavirus vaccine against cervical dysplasia in Manitoba, Canada" J Clin Oncol 2013; DOI: 10.1200/JCO.2013.52.464.