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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Largest oral HPV study in England shows infection rates lower than expected

Infection rates of high risk human papillomavirus (HR-HPV) oral infection in England are lower than expected, compared to previous US studies.

The research, conducted by the University of Sheffield, also strengthens evidence that smoking and sexual behaviour were shown to be risk factors for oral HPV infection, which can lead to oropharyngeal (throat) cancer.

This timely study published in the British Medical Journal Open, led by Professor Hilary Powers, Dr Vanessa Hearnden and Dr Craig Murdoch and funded by the World Cancer Research Fund UK, coincides with the announcement of a new UK HPV vaccine programme for boys which will reduce the risk of HR-HPV related cancers.

Rates of oropharyngeal cancers are increasing worldwide, attributable to an increase in the rate of oral infection with HR-HPV.

This new study of 700 men and women in Sheffield, which is the largest of its kind in England, looked for HR-HPV infection and also asked participants lifestyle questions relating to their sexual history and tobacco use.

A total of 2.2 per cent of people were infected with oral HR-HPV infection with 0.7 per cent positive for HPV16 or HPV18. There are large variations in oral HR-HPV prevalence globally however this study showed lower rates compared to previous Scottish and US studies which both found 3.7 per cent of individuals positive for oral HR-HPV.

Former smokers were significantly more likely to be HR-HPV positive compared with those that had never smoked. The study also found that participants with a greater number of sexual or oral sexual partners were more likely to be HR-HPV positive.

Dr Vanessa Hearnden, from the Department of Materials Science and Engineering at the University of Sheffield, said: "Previous studies have been US-focused or in smaller UK studies in London or Scotland. This is the first study in the North of England and found lower rates of oral high-risk human papillomavirus infection.

"We fully support the newly announced HPV vaccination programme for boys which will reduce the risk of HPV related cancers including throat cancer in men and will also provide further prevention of cervical cancers through herd immunity.

"However, we found the majority of individuals testing positive for high risk strains of HPV were actually positive for strains other than those covered by the current vaccine (HPV 16 and HPV 18). This shows the need to consider newer vaccines which protect against more HPV strains in the future and for individuals to be aware of lifestyle risk factors such as number of sexual partners and tobacco use."

Dr Craig Murdoch, from the University of Sheffield's School of Clinical Dentistry, said: "Many people associate the HPV virus with cervical cancer but there is less recognition of the fact that HPV causes oropharyngeal cancer, and unfortunately, the prevalence of this cancer has increased dramatically in the past few years.

"The Sheffield Head and Neck Oncology Research Team are conducting research into HPV-related oral cancer in order to find better ways to treat this disease and improve quality of life."

Dr Kate Allen, Executive Director of Science & Public Affairs for World Cancer Research Fund International, said: "This study confirms the importance of lifestyle risk factors in prevention of the disease and sheds new light on the rates of oral HR-HPV infection in England."

Source: https://www.sciencedaily.com/releases/2018/08/180820094502.htm

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

Human Papillomavirus and Cancer

Human Papillomavirus (HPV)

The human papillomavirus, or HPV, is a type of virus that infects the skin and the cells lining body cavities. For most people, the infection will get better on its own and they will never know they had it. 

There are different types of HPV:

Some infect the skin, usually on the fingers and hands. These can cause minor problems, such as common skin warts and verrucas.

Others infect the genitals, mouth and throat. These can cause genital warts, or more rarely, cancer.

From this point onwards, the discussion is on genital and oral HPV, as these types are the ones which can cause cancer.

HPV is a very common infection. Around 8 out of 10 people will be infected with the virus at some point in their lives. It usually doesn’t cause any symptoms and most people will never know they had it. HPV spreads through close skin-to-skin contact, usually during sexual activity including oral sex. Having a high number of sexual partners does increase the chances of infection. 

HPV infection usually causes no problems at all. But in some people the infection will stay around for a long time and become persistent. Around 13 types of HPV can cause cancer. These are called ‘high-risk’ types. People with persistent infections with ‘high-risk’ HPV types are those who are most likely to go on to develop cancer.

HPV & Cancer

The main type of cancer linked to HPV infection is cervical cancer. Virtually all cases of cervical cancer are caused by HPV. About 3,100 cases of cervical cancer are diagnosed in the UK each year.

HPV can also cause cancer in other genital areas, like the vagina, vulva, penis, and anus. It can also cause some types of cancer of the mouth and throat.

The majority of vaginal, vulval, penile and anal cancers are caused by HPV. But they are less common than cervical cancer. Men who have sex with men may be at increased risk of anal cancer.

HPV infection also increases the risk of some types of mouth and throat cancers. Rates of mouth cancer, especially tongue and tonsil cancers, are on the increase, particularly in people in their 40s, 50s and 60s.30–34 And the evidence suggests that the proportion of cases linked to HPV is rising.

How HPV leads to Cancer

HPV can cause cells to divide more than usual. Fast cell growth can cause warts to develop, but often it doesn’t cause any symptoms at all. The types of HPV that cause warts are not the same types that cause cancer.

In persistent ‘high-risk’ HPV infections, the virus can damage DNA and cause cells to start dividing and growing out of control. This can lead to cancer.

HPV Vaccine

HPV can cause changes to the DNA in our cells that make them more likely to turn cancerous. So by protecting against HPV infection, we can help prevent those changes and reduce the risk of cervical cancer.

HPV Vaccination for Women

Since 2008, girls aged 11-13 have been offered a vaccination against the two most common ‘high-risk’ types of HPV, HPV 16 and 18. Together, these two types cause about 7 out of 10 cervical cancers. Girls up to the age of 18 can request vaccination through the NHS if they weren’t vaccinated routinely. The HPV vaccine has been proven to be safe and effective.

The HPV vaccine currently used in the UK (Gardisil) also protects against HPV 6 and 11, which are the HPV types that cause most genital warts.

The HPV vaccine doesn’t protect against all types of HPV, so screening is still important, even if you have been vaccinated.

HPV Vaccination for Men

As HPV is linked to cancers in men as well as women, offering HPV vaccination to men would help reduce the risk of disease. Men who have sex with men have a higher risk of anal cancer than men who don’t.

From April 2018, the vaccine is being rolled out men who have sex with men in all sexual health and HIV clinics across the UK.

The Joint Committee for Vaccination and Immunisation are also currently considering whether to offer HPV vaccination to all teenage boys as well as girls.

Cervical Screening for HPV

Cervical screening aims to pick up early cell changes that are caused by HPV and remove these cells before they have a chance to become cancerous. This is done by taking a sample of cells and sending them to a lab where they are tested to see if they are normal (cytology). If the cells look abnormal, they will be tested for HPV to see if they are more likely to become cancerous. If they test positive for HPV, the cells will be removed.

Source: https://www.cancerresearchuk.org/about-cancer/causes-of-cancer/infections-hpv-and-cancer/hpv-and-cancer

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