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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Co-Infections of Sexually Transmitted Diseases

With early diagnosis, proper monitoring and care, most of the illnesses caused by HIV can be prevented. They are much less frequent than they were before effective anti-HIV drugs became available.

There are a number of infections and illnesses that can develop in people who are living with HIV, particularly those people who are not able to take anti-HIV drugs. Some of these life-threatening infections are called opportunistic infections. These only occur if your immune system is quite weakened (usually in the absence of anti-HIV drug therapy) and your body becomes vulnerable to infections that would not affect you otherwise.

Co-infections are illnesses that can occur in people with normal immune systems, but they can impact how you live with HIV.

Some types of cancers are thought to be more common in people with HIV.

Increasingly, the distinction between these different types of infections—life-threatening infections, co-infections and even some cancers—is blurred, as some infections can fit all three categories (for example, human papillomavirus is a co-infection which can lead to cervical and anal cancer).

Life-threatening infections

These infections occur only when a person’s immune system has been seriously weakened by HIV due to lack of diagnosis and/or anti-HIV treatment. HIV attacks immune cells called CD4+ cells, which are needed for fighting off infections and some cancers. A normal CD4+ cell count in an HIV-negative person is around 500 to 1,500 cells in each cubic millimetre (mm³) of blood. If your CD4+ cell count gets lower, your immune system becomes unable to fight off a number of common viruses, bacteria and parasites. These infections can then take hold. (They are sometimes called opportunistic infections because they take advantage of your weakened immune system.)

Life-threatening infections are uncommon now, since most people take anti-HIV drugs, which controls their viral load, raises their CD4+ levels and stabilizes and restores immune system function. This helps prevent life-threatening infections caused by HIV.

The main danger nowadays is in not finding out you are HIV-positive until your CD4+ cell counts are already so low that you are at risk or are already sick with a life-threatening infection.

The more common life-threatening infections are listed in the accompanying table. Some of these can still occur in people with relatively high CD4+ levels but are more serious when the immune system is weakened.

Life-threatening infections include a lung infection called Pneumocystis pneumonia (PCP), an eye infection caused by cytomegalovirus (CMV), a brain infection called toxoplasmosis, and a generalized infection called Mycobacterium avium complex (MAC). If it happens that you find out you have HIV when your CD4+ cell count is very low, there are drugs you can take to prevent these infections. This is called prophylaxis.

Co-infections

Hepatitis

These are infections that can occur even in people with HIV who have adequate CD4+ levels—just as they can occur in people who do not have HIV. They are called co-infections because you have them along with HIV. Co-infections can complicate your HIV treatment and make living with HIV more difficult. HIV can also complicate the treatment and diagnosis of a co-infection. Although they may occur at normal CD4+ levels, the lower your CD4+ cell count is, the more of a problem they can be.

Chronic hepatitis is an increasingly common co-infection for many people with HIV. Hepatitis is a liver condition usually caused by viruses called hepatitis A, hepatitis B or hepatitis C. These viruses infect the liver and can cause jaundice (yellow skin and eyes), dark urine, pale stool and severe fatigue. It is a good idea for your doctor to check regularly for these infections. Hepatitis B and C are transmitted by:

·         blood-to-blood contact through sharing drug-using equipment, or personal care items like razors;

·         transfusion of blood and blood products before 1992 when the Canadian system started screening;

·         unprotected sexual intercourse;

·         being passed from mother to child during childbirth.

Hepatitis A is another, usually less serious, viral infection of the liver. Hepatitis A is spread through feces (shit), and you can be infected by contaminated food (for instance, if someone handling your food has hepatitis A and did not wash his or her hands). If you are exposed to hepatitis A, it can make you quite sick for a few weeks, but your immune system usually clears it. Hepatitis A very rarely causes permanent damage unless you already have hepatitis B or C as well.

If infected with the hepatitis A or B virus, some people get over the initial liver infection and develop immunity. This is much less likely to happen in people with HIV who are co-infected with hepatitis C. Without treatment, people can develop chronic hepatitis, remain infectious to others and develop ongoing liver problems.

As described below, there are vaccinations that will prevent you from getting hepatitis A and B infection. There is no vaccination available for hepatitis C.

Effective antiviral treatments are available for both hepatitis B and C infection. Treatment can cure hepatitis C and keep hepatitis B under control. There are interactions between drugs to treat hepatitis and HIV, so make sure you see a doctor with expertise in both conditions.

Tuberculosis (TB)

TB is a concern for people with HIV because it is so easily spread, especially in places where people live close to each other, in poverty and without adequate medical care.

TB usually infects the lungs, but it can also affect the bones, brain and other organs in your body. TB is spread through the air when someone with active TB coughs or sneezes. Diagnosis of TB is done by skin tests, tests of your sputum (phlegm) and chest X-rays. There are effective treatments for TB, but they need to be taken every day for many months. Missing doses, or stopping before the full treatment period is over, can cause the TB infection to become drug-resistant and much more difficult to treat. People with HIV with a history of previously treated TB may have it reactivate (come back again) if their immune system weakens.

Herpes infections

Herpes is a family of viruses that includes:

·         Herpes simplex, which causes cold sores on the mouth or painful sores on the genitals.

·         Varicella-zoster, which initially causes chicken pox and when reactivated causes painful sores called shingles anywhere on the skin.

Herpes infections are common and are often transmitted by physical contact and sex. Usually, the immune system keeps herpes infection under control until something like stress or a high fever brings the sores out in an outbreak lasting seven to 10 days, or longer. The lower your CD4+ cell count, the more frequent outbreaks may be. They may also last longer.

People with HIV with extremely weak immune systems (CD4+ cell counts less than 100 cells/mm3) are at risk for herpes infections all over the body (disseminated herpes) or in the brain (herpes encephalitis). People with frequent herpes outbreaks (even with normal CD4+ levels), or people at risk for more serious herpes infections, can take antiviral drugs—usually valacyclovir or similar drugs—to keep the herpes virus suppressed.

Fungal infections

Fungal or yeast infections can happen whether you are HIV-positive or not. Women get vaginal yeast infections, and men and women can get athlete’s foot or fungal infections on the skin or nails. The more weakened your immune system is, the more this can be a problem.

Even people with moderate CD4+ cell counts can get a fungal infection in the mouth or vagina called candidiasis or thrush. Antifungal creams, pills and vaginal suppositories are available to treat these problems, and probiotic supplements or yoghurts with friendly bacteria may also help. Watch your diet because the more sugar you eat, the more susceptible you are to fungus, which loves sugar.

Sexually transmitted infections

Some of the infections discussed above can be passed on in many ways, including through sex. Some other infections, like chlamydia, gonorrhea and syphilis, and the virus HPV, are virtually always transmitted sexually. 

Cancers

Cancer is the abnormal and uncontrolled growth of cells in different parts of the body. These cancerous growths then destroy healthy cells and cause serious illness. A normally functioning immune system acts to suppress this abnormal growth of cells.

People with HIV can become more vulnerable to certain types of cancer. Some of these cancers occur only when the immune system is weakened. Other cancers seem to be more common in people with HIV even when their immune system is relatively healthy.

Kaposi’s sarcoma

Kaposi’s sarcoma (KS), a rare form of skin cancer, is caused by a member of the herpes virus family and can be life-threatening.  It causes purple lesions on the skin that looked like bruises. Although slow growing, if it spreads to internal organs it could lead to illness and death. In the early days of HIV, it was quite common in people living with HIV. When HAART was introduced, KS became uncommon and now only occurs in people with very weak immune systems.

Non-Hodgkin’s lymphoma

When the cells in the lymph nodes become cancerous, this is called lymphoma. The non-Hodgkin’s type of lymphoma (NHL) is more common in people with HIV. The symptoms of NHL may include persistently swollen lymph glands, fevers, chills and sweats and weight loss. In the case of central nervous system lymphoma, the symptoms are often headaches and seizures.

Diagnosis of lymphoma, like many cancers, is done by biopsy where a sample of tissue from a swollen lymph node is examined under the microscope for evidence of abnormal cells. In the event of central nervous system lymphoma, the diagnosis is made by examining cerebrospinal fluid tapped from the spine. Lymphoma is usually treated by chemotherapy, where powerful anti-cancer drugs are injected into the vein on a regular basis, and/or radiation therapy where high-powered X-rays are directed at the cancer cells.

Cervical cancer

The cervix is the opening of the uterus (womb) inside a woman’s vagina. Sometimes abnormal cells can start to grow on the cervix, usually as a result of HPV infection. Over time, these abnormal growths can become a pre-cancerous condition called cervical dysplasia. If dysplasia is not found and treated, it can become cancer.

To prevent this, all women should have annual Pap tests to look for dysplasia from a small scraping of cells from the cervix. Women with a history of genital warts or cigarette smoking should have Pap exams more frequently. If dysplasia is found, it is usually treated with a laser in a procedure called colposcopy.

The HPV vaccine will protect women from some, but not all, strains of HPV and so it is hoped it will prevent some cases of cervical cancer. However, this vaccine is effective only if it is given before women have been exposed to the HPV strains the vaccine targets.

Anal cancer

Cancer in the anal canal of men and women is similar to cervical cancer. It is also usually caused by infection with HPV and, like cervical cancer, develops over time from dysplasia to cancer. Risk factors include a history of anal sex and/or genital warts. Both men and women with HIV are thought to be more vulnerable to this form of cancer. 

Other cancers

There are many other forms of cancers that people with HIV are thought to be at slightly higher risk for, even without immune suppression. These include Hodgkin’s lymphoma, lung cancer, skin cancer, vaginal cancer in women and testicular and prostate cancer in men. Fortunately, these cancers are not common and can often be successfully treated if they do occur in people with HIV who maintain healthy immune systems with effective anti-HIV drugs.

Source: http://www.catie.ca/en/practical-guides/managing-your-health/12

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