HPV blood test shows promise for tracking head and neck cancer after treatment

A new blood test developed by University of North Carolina Lineberger Comprehensive Cancer Center researchers shows promise for tracking HPV-linked head and neck cancer patients to ensure they remain cancer-free after treatment.

Researchers will present preliminary findings at the 60th Annual Meeting of the American Society for Radiation Oncology in San Antonio on Tuesday, Oct. 23. Their study evaluated a blood test for HPV-linked oropharyngeal squamous cell carcinoma, which is a cancer of the back of the throat. The findings demonstrated the test could be an effective and less costly alternative for monitoring for cancer recurrence after radiation treatment.

"The goal of this study was to evaluate whether this test can be used to track patients who are completely asymptomatic, and thought to have no active cancer," said UNC Lineberger's Gaorav P. Gupta, MD, PhD, assistant professor in the UNC School of Medicine Department of Radiation Oncology. "We already knew that our test was very sensitive and specific, but we did not know the degree to which it would be useful in early detection of disease recurrence in patients who are otherwise thought to be disease-free."

HPV, or the human papillomavirus, is the most common cause of sexually transmitted infection in the United States, according to the U.S. Centers for Disease Control and Prevention. Infection with certain strains of HPV can cause cervical cancer in women, genital cancers in both men and women, and cancer of the oropharynx, which is the back of the throat, including the base of the tongue and tonsils. The CDC estimates that approximately 70 percent of oropharyngeal cancer cases diagnosed in the United States are probably caused by HPV, which accounts for nearly 13,000 cases per year.

Gupta and his colleagues developed a blood test that can detect fragments of HPV's genetic material that have been released into the blood by dying cancer cells.

"We realized it is important to distinguish HPV DNA that's being released by dying tumor cells from the natural HPV DNA that is present during a viral infection," Gupta said. "Our method accomplishes this feat, thus making it a more sensitive and specific test for cancer."

For their study, the researchers followed 89 patients with HPV-associated oropharyngeal squamous cell carcinoma who received chemotherapy and radiation treatment. They administered the blood test before and during treatment, and then during follow-up visits. The patients received scans three months after treatment, and then came back for clinical exams every two to four months during the first two years, and then every six months in years three through five. Patients received X-rays or CT scans every six months, and again if they had positive HPV results.

"We are detecting subclinical disease with this blood test, and the imaging patients received confirmed those findings," said UNC Lineberger's Bhishamjit S. Chera, MD, associate professor in the UNC School of Medicine Department of Radiation Oncology and the study's co-corresponding author. Chera presented the findings from the study at the ASTRO meeting.

Of the 70 patients whose blood tests were negative three months after treatment, none developed recurrence. Nineteen patients had positive blood tests, and eight of those patients developed recurrence. Physicians are continuing to monitor the remaining eleven who had positive blood tests but no evidence of recurrence.

"The most striking finding of our study is that of the patients who did not have any signal using our blood test, none of them developed disease recurrence," Chera said. "That raises the question: Do we need to be scanning these patients? Scans come with a lot of cost, and because of the cost, we're not able to do it as frequently. Patients end up having a lot of anxiety from one scan to the next, wondering if their cancer has come back. This blood test could spare patients the need for additional imaging and potentially alleviate some anxiety."

The researchers say the next steps will involve investigating whether the test can be used prospectively to monitor patients and to make decisions that could avoid unnecessary imaging, thereby reducing costs. They also see additional applications for the blood test, including monitoring for other HPV-linked cancers, including cervical cancer.

"We are confident this blood test will be translatable to other cancers driven by HPV, and as a monitoring tool for cancer diagnosis," Chera said. "We strongly believe that this test may also have a role in screening, not just for oropharyngeal cancer, but also cervical or anal cancers, possibly in a general population setting, or at least in patients who may be at higher risk of developing these conditions."

In addition to Chera and Gupta, other authors include Sunil Kumar, PhD; Colette Shen, MD, PhD; Robert Amdur, MD; Roi Dagan, MD; Jared Weiss, MD; Juneko Grilley-Olson, MD; Adam Zanation, MD; Trevor Hackman, MD; Jeff Blumberg, MD; Samip Patel, MD; Brian Thorp, MD; Mark Weissler, MD; Nathan Sheets, MD; and William Mendenhall, MD.

The study was supported by the University Cancer Research Fund, Burroughs Wellcome Fund, the University of North Carolina School of Medicine Department of Radiation Oncology, UNC Lineberger and the University of Florida School of Medicine Department of Radiation Oncology.

Intellectual property related to the test and held by the University of North Carolina at Chapel Hill has been licensed to Naveris, a company in which Chera and Gupta hold equity stakes.

Source: https://www.sciencedaily.com/releases/2018/10/181023085744.htm

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Screening HPV infection alone more accurate than Pap test in detection of cervical cancer

Screening for human papillomavirus (HPV) infection alone gives more accurate results than Pap (smear) testing for cervical cancer, say the authors of two papers to published today in the journal Gynecologic Oncology. HPV infection causes almost all cervical cancer, and it is estimated that more than half of sexually active people are infected with HPV at some point in their lives. Now new research has shown that in many cases, an HPV test alone can be used for cervical cancer screening instead of a Pap or cotesting with both an HPV and a Pap test, the researchers say.

In the first paper1, Dr Warner Huh, from the Department of Gynecologic Oncology, University of Alabama, Birmingham, USA, sets out the findings of a panel convened to provide guidance on using HPV as the first-line primary screening test. The panel included representatives from all the major US organizations involved in cervical cancer screening, and addressed questions related to the safety and effectiveness of HPV testing for primary screening and whether it could be considered as an alternative to the screening methods currently in use in the US. The panel was convened because of an application to the Food and Drug Administration (FDA) for an existing HPV test to be used for primary HPV cervical cancer screening. The guidance was based on a literature review and also on review of data from the ATHENA study which was conducted to support the primary screening application to the FDA.

"We found that, in patients aged 25 years and upwards, primary HPV testing performed better than a Pap alone, and we recommend that such tests should be carried out no sooner than every three years. This is an important advance in cervical cancer screening because it offers a better reassurance of low cancer risk compared to Pap screening, which is also carried out at three year intervals," Dr Huh said.

Infection with just two HPV genotypes, 16 and 18, is responsible for about 70% of all invasive cervical cancers worldwide. The panel recommends that patients testing positive for either of these two high risk genotypes should have immediate colposcopy - a procedure using a lighted magnifying device that allows doctors to see abnormal areas in the cervix that would be missed by the naked eye. Women with one of the 12 other HPV genotypes can be followed-up in 12 months with repeat testing with both the HPV test and a Pap.

"We believe that there is still considerable confusion over the three current screening options, and the intervals at which they should be performed. We hope that our deliberations will go some way towards reducing this uncertainty. However, I would still like to see more data from the US, and evidence from other countries using primary HPV screening such as Australia and The Netherlands. But in the absence of data to the contrary, we believe that primary HPV testing has potential to further reduce cervical cancer in the US," Dr Huh said.

The second paper2 reveals end-of-study results of the ATHENA trial which evaluated safety and effectiveness of HPV primary screening as an alternative to Pap in women of 25 years and older. 42,209 women in this age group were enrolled into the trial and had both Pap and HPV testing. Those with abnormal Pap test results and those who were HPV positive were referred for colposcopy.

"We found that HPV primary screening was as effective in women aged 25 years and over when compared to Pap alone for women 25 and 29 and cotesting for those aged 30 and over. However, HPV screening alone requires only one test, and this is important for many women who may not be able to afford the cost of two tests," said Dr Thomas Wright, a Professor Emeritus of Pathology and Cell Biology at Columbia University, New York, USA.

To determine the impact of starting HPV screening at different ages, the researchers compared the prevalence of HPV positivity and Pap abnormalities as well as the three year detection rate of high-grade cervical disease by age group. They found that although HPV positivity was almost twice as high in women aged 25-29 as it was in women aged 30-39, HPV testing identified about twice as many high-grade cervical disease cases in women aged 25-29 than did the Pap.

"When Pap screening is used in this age group, the women with missed high-grade cervical disease are told to return in three years for repeat screening and some are likely to develop invasive cervical cancer", said Dr Wright.

"Our results, from the first prospective US study to evaluate the performance of HPV primary screening, have shown clearly that this new screening approach should be considered as an option for women 25 years and older", Dr Wright said. However, he added that the recent FDA approval for HPV primary screening is limited to a single commercially available HPV test and to only one of the two widely utilised liquid-based Pap tests. "In order to facilitate the widespread adoption of this safe and effective method of screening, it would be advantageous to have additional HPV tests and the other liquid-based Pap tests approved. We hope that our research will help reduce morbidity and mortality from cervical cancer worldwide," he said.

Source: https://medicalxpress.com/news/2015-01-screening-hpv-infection-accurate-pap.html

NUCLEIC-ACID AMPLIFICATION TESTS

NUCLEIC-ACID AMPLIFICATION TESTS

Nucleic-acid amplification tests, also known as NATs or NAATs, are used to identify small amounts of DNA or RNA in test samples. When it comes to STD testing, there are NATs available that can detect a variety of different STDs. In fact, most urine tests for STDs are performed using nucleic-acid amplification tests.

MECHANISM

A NAT uses a series of repeated chemical reactions to make numerous copies of the DNA or RNA that doctors are trying to detect. These reactions amplify the signal of the nucleic acids in the test sample so that they are easier to identify. It's much simpler to find 10,000 copies of a gene than 10. 

once the amount of DNA or RNA has been increased in the sample using PCR or LCR, more conventional tests are used to detect it. These tests usually involve some form of nucleic acid hybridization. In those tests, the sample is probed with an artificially produced complementary strand of DNA or RNA that has been labelled in some way that makes it easy to detect. It may help to picture it as a glow in the dark tag that only sticks to one very specific piece of identifying information.

STD TESTING

Nucleic-acid amplification tests are incredibly useful for STD testing. They allow doctors to detect an STD pathogen even when only a very small number of organisms are present. It is this sort of technology that has made it possible to do urine testing for STDs that were previously only detectable by swab.

Furthermore, since nucleic-acid amplification tests are incredibly sensitive to even small amounts of viral DNA, they are very important for screening the blood supply. These tests make it possible to detect tiny amounts of HIV and other blood-borne pathogens that might otherwise be missed.

There are also non-amplified nucleic acid tests available for certain STDs, such as gonorrhea and chlamydia. Non-amplified nucleic acid hybridization tests are more likely to be used when large amounts of bacterial or viral DNA (or RNA) would be expected to be present, such as in a urethral swab or in a bacterial culture sample. In such circumstances, no amplification is necessary. In these samples, if DNA or RNA is present, it should be present in detectable amounts.

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No more ‘sledgehammer’: As gonorrhea grows resistant to antibiotics, researchers look to bespoke treatments

With antibiotic resistance on the rise, the days when doctors and clinics could rely on one treatment to cure all gonorrhea cases may be waning.

In fact, clinicians may find that some of their patients respond best to drugs of the past. But how will they know which patients?

To answer that question, a handful of researchers and companies are trying to develop rapid, point-of-care diagnostics that would signal which drugs work for a given patient and permit clinicians to tailor treatment to the bacterial strain. A future, in other words, of bespoke treatment, in which a greater variety of drugs are used to treat a very common sexually transmitted disease — potentially prolonging the utility of several antibiotics.

“It would allow for smarter medicine,” Dr. Jeffrey D. Klausner, a professor of infectious diseases medicine at the University of California, Los Angeles, told STAT. “Right now, we’re treating gonorrhea with a sledgehammer, we’re treating everything with the same exact regime. And it’s not a surprise that the organism will become resistant to what we’re currently using.”

Klausner has collaborated with several companies working in this area but has not received payment from the companies. The companies have made contributions to UCLA, he said.

Gonorrhea is spread by sexual contact, and infection can occur in the genitals, the rectum, and the throat. The World Health Organization estimates that about 78 million people a year are infected with gonorrhea; roughly 820,000 of those infections occur in the United States.

Left untreated, gonorrhea can cause pelvic inflammatory disease and infertility in women and sterility in men. Infection increases a person’s risk of contracting HIV. Babies born to an infected woman can develop blindness.

From a treatment point of view, the ideal regimen for curing gonorrhea is an oral antibiotic — and was long the standard of care. But gonorrhea is a wily bacterium, adept at learning tricks that allow it to evade the power of antibiotics. One after another, the available drugs have started to fail.

For several years, the recommended regimen for gonorrhea has been a dual-therapy approach, the thinking being that it is harder for resistance to develop to a drug combination than to a single drug. The current recommended therapy is one injection of the antibiotic ceftriaxone followed by a multiday course of azithromycin. But even that approach is starting to show signs of weakness.

At the same time, there has been a belief that, even as medicine has moved on, there is life left in the drugs that have been abandoned — if you could figure out in whom they would work.

“We’ve been treating empirically and a lot of times ignoring the fact that the majority of organisms, the majority of infections we’re seeing, are actually fully susceptible to the old drugs,” said Fred Tenover, vice president for scientific affairs at Cepheid Inc., a California-based maker of molecular diagnostics.

“So now we have to have a change in philosophy and say: You know what? Now it’s time to go and do what we do for every other infection, which is actually define what the best therapeutic is up front.”

Cepheid is exploring the idea of developing such a test, Tenover said. “We’re trying to figure out what it would look like and what it would cost,” he said. “This is not in our pipeline officially. It’s something we’re looking at, something we haven’t committed to, but we have figured out how to make the assay.”

Other smaller companies are in the hunt. SpeeDx, an Australian-American firm, has a test in development that it hopes will receive licensing approval in Europe this autumn. The company is currently conducting a clinical trial in the United States in hopes of with the goal of filing for approval with the Food and Drug Administration.

The test both diagnoses gonorrhea and indicates whether the infecting strain can be treated with Cipro, said CEO Colin Denver. It currently would need to be processed by a central lab, but the plan is to develop the assay as a point-of-care test that could be used in a clinic or doctor’s office.

Shield Diagnostics, of Santa Clara, Calif., has a similar idea in mind. The company has a proprietary testing platform; CEO Fred Turner said it will roll out its first test this fall. The test can diagnose gonorrhea and ascertain if the strain is susceptible to Cipro.

For now, it is not a point-of-care test; that may be three or four years down the road, Turner said. In the meantime, Shield will process the tests in its own laboratories. Turner said the testing will likely take two to three days. Ideally, over time, both companies hope their assays will be expanded to give a broader resistance profile, one that indicates whether other drugs would be effective.

“Our ultimate goal is to have clinicians utilize a test-and-treat algorithm so that you don’t have to use these empiric therapies,” Denver said.

A patient would come into a clinic and specimens to test would be taken. While he or she is seeing the doctor, the test would be run. Within an hour or so, the doctor would know whether a single dose of Cipro or cefixime (also an oral drug) would do, or whether the ceftriaxone-azithromycin combination would be the better option.

“It’s like personalized medicine — your individual infection treated with the antibiotic you know is going to work,” Denver said.

But in order for these types of tests to be truly useful, they’ll need to be affordable and produce a rapid answer, said Dr. Lindley Barbee, an assistant professor of infectious diseases at the University of Washington and medical director of the Public Health – Seattle & King County STD Clinic. Not a day or two later, but while the person was in the clinic.

Many clinics that treat sexually transmitted infections are government funded, Barbee noted: “You have to get the cost low enough to make it worthwhile.”

That’s clearly a factor that has slowed development of these tests. “If you say to somebody who’s paying $10 for this test now, ‘Well, I can better define your therapy but it’s going to cost $17 a test, not $10 a test,’ that may be beyond the reach of a lot of public health clinics or STI clinics. And that’s probably what it would take,” said Cepheid’s Tenover.

“To date the return on investment has not been positive enough to make these commercially available,” he said. “That may be changing. And I think as we talk more and more about the spread of superbug gonorrhea, people may be more and more interested in doing this. But in the past there hasn’t been a market for these types of tests.”

Source: https://www.statnews.com/2018/07/17/gonorrhea-grows-resistant-to-antibiotics-researchers-look-to-bespoke-treatments/