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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Standard treatment for common STD doesn't eliminate parasite in some women

A new study led by an infectious disease epidemiologist at Tulane University School of Public Health and Tropical Medicine could change the way doctors treat a common sexually transmitted disease.

Professor Patricia Kissinger and a team of researchers found the recommended single dose of medication isn't enough to eliminate trichomoniasis, the most common curable STD, which can cause serious birth complications and make people more susceptible to HIV. Results of the research are published in Lancet Infectious Diseases.

Globally, an estimated 143 million new cases of trichomoniasis among women occur each year and most do not have symptoms, yet the infection is causing unseen problems. The recommended treatment for more than three decades has been a single dose of the antibiotics metronidazole or tinidazole.

The researchers recruited more than 600 women for the randomized trial in New Orleans; Jackson, Mississippi; and Birmingham, Alabama. Half the women took a single dose of metronidazole and the other half received treatment over seven days.

Kissinger and her team found the women who received multiple doses of the treatment were half as likely to still have the infection after taking all the medication compared to women who only took a single dose.

"There about 3.7 million new cases of trichomoniasis each year in the United States," Kissinger said. "That means a lot of women have not been getting inadequate treatment for many decades."

Trichomoniasis can cause preterm delivery in pregnant women and babies born to infected mothers are more likely to have low birth weight. The parasite can also increase the risk of getting or spreading HIV.

Kissinger believes the CDC will change its treatment recommendations because of the results of this study.

"We need evidence-based interventions to improve health," Kissinger says. "We can no longer do something because it's what we've always done. I hope that this study will help to change the recommendations so that women can get the proper treatment for this common curable STD."

Source: https://www.sciencedaily.com/releases/2018/10/181007084044.htm

During HIV infection, antibody can block B cells from fighting pathogens

For the first time, scientists have shown that in certain people living with HIV, a type of antibody called immunoglobulin G3 (IgG3) stops the immune system's B cells from doing their normal job of fighting pathogens. This phenomenon appears to be one way the body tries to reduce the potentially damaging effects of immune-system hyperactivity caused by the presence of HIV, according to the investigators, but in so doing, it also impairs normal immune function.

The research was led by scientists in the Laboratory of Immunoregulation and the Laboratory of Immunogenetics at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The investigators made their discovery by analyzing blood samples from 83 HIV-uninfected, anonymous donors and 108 people who were living with HIV at various stages of infection. The people living with HIV came from a variety of racial and ethnic backgrounds. Some of these people were being treated for their infection, while others had not yet begun therapy.

The scientists observed that IgG3 appeared on the surface of B cells only under certain conditions. It appeared in people living with HIV, but not in HIV-uninfected people. Also, IgG3 predominantly appeared on B cells of people of African American or black African decent during the chronic phase of untreated HIV infection when the virus was not adequately controlled.

A site on B cells called the B-cell receptor normally binds to foreign entities such as pathogens. This binding stimulates the B cell to produce many copies of the antibody form of the receptor, which can trap a pathogen and mark it for destruction. The scientists found that IgG3 short-circuits this process in certain people living with HIV by docking on the B-cell receptor, blocking it from adequately responding to the pathogen or other intended target. The researchers also demonstrated how other components of the immune system contribute to IgG3 interference with normal B-cell function during HIV infection. Finally, they showed that IgG3 stops binding to B-cell receptors when a chronically infected person starts treatment that controls the virus, illustrating that the IgG3 activity is directly linked to the presence of HIV during chronic infection.

Source: https://www.sciencedaily.com/releases/2018/08/180813125236.htm

HIV RNA expression inhibitors may restore immune function in HIV-infected individuals

Immune activation and inflammation persist in most treated HIV-infected individuals and is associated with excess risk of mortality and morbidity. A new study by Boston University School of Medicine (BUSM) researchers suggests that use of HIV RNA expression inhibitors as adjunct therapy might diminish atypical inflammation and restore immune function in HIV-infected individuals on combination antiretroviral therapy (cART).

HIV-1-infected individuals have excess risk of developing non-AIDS complications such as cardiovascular atherosclerosis, neurocognitive dysfunctions, non-AIDS cancers, osteoporosis, and renal disorders. Systemic chronic immune activation has been postulated to lead to these non-AIDS complications.

Despite long-term viral suppression by cART, it has remained unclear how chronic inflammation is induced in HIV-infected individuals. In this study, BUSM researchers identified a mechanism of HIV-1-induced chronic immune activation and T cell dysfunction. In studies performed with primary human macrophages and T cells, they found that persistent infection of macrophages with HIV-1 and expression of intron-containing HIV-1 RNA alone even in the absence of infectious virus production lead to induction of type I interferon (IFN-I)-dependent pro-inflammatory responses and immune exhaustion of co-cultured T cells. They believe that these findings might provide an explanation for the observed chronic inflammation-associated morbidities in HIV-infected individuals who are on cART.

"We hope our study will broaden knowledge of host-HIV interactions and might help to reduce inflammation-associated disorders caused by chronic viral infections," said Rahm Gummuluru, PhD, corresponding author and associate professor of microbiology.

Source: https://www.sciencedaily.com/releases/2018/08/180827102648.htm

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“AIDS-defining” conditions

HIV is a virus that attacks CD4 cells (T cells). These white blood cells serve as helper cells for the immune system. CD4 cells send a biological SOS signal to other immune system cells to go on the offensive against infections.

When a person contracts HIV, the virus merges with their CD4 cells. The virus then hijacks and uses the CD4 cells to multiply. As a result, there are fewer CD4 cells to fight infections.

Opportunistic infections and diseases

With HIV, a weakened immune system increases vulnerability to several opportunistic infections, cancers, and other conditions. The CDC refers to these as “AIDS-defining” conditions. If someone has one of these conditions, the HIV infection has advanced to stage 3 HIV (AIDS), regardless of the number of CD4 cells in their blood.

Following are some of the more common opportunistic diseases. Becoming knowledgeable about these health risks is the first step in protecting against them.

Candidiasis

Candidiasis encompasses several infections in different areas of the body caused by Candida, a genus of fungi. These infections include oral thrush and vaginitis. A fungal infection is considered AIDS-defining when found in the esophagus, bronchi, trachea, or lungs.

Powerful and sometimes quite toxic antifungal medications are used to treat candidiasis. A healthcare provider will recommend a specific medication based on the location of infection.

For instance, they may prescribe these medications for vaginitis caused by candidiasis:

• butoconazole (Gynazole)
• clotrimazole
• miconazole (Monistat)

If systemic infection is present, treatment may include medications like:

• fluconazole (Diflucan)
• itraconazole (Sporanox)
• posaconazole (Noxafil)
• micafungin (Mycamine)
• amphotericin B (Fungizone)

Cryptococcal meningitis

Cryptococcus is a common fungus found in soil and bird droppings. Some varieties also grow in areas surrounding trees, and one variety particularly prefers eucalyptus trees. If inhaled, Cryptococcus may cause meningitis. This is an infection of the membranes around the brain and spinal cord.

Very potent (and quite often toxic) antifungal medications are used to initially treat cryptococcal meningitis, as are frequent spinal taps. These medications may include in combination:

• amphotericin B
• flucytosine (Ancobon)
• fluconazole
• itraconazole

This condition can be fatal if not treated promptly. Long-term suppressive therapy is often used with somewhat less toxic medications for people with HIV.

Cryptosporidiosis

A tiny parasite that lives in the intestines of humans and animals is responsible for cryptosporidiosis. Most people get the disease by drinking contaminated water or eating contaminated produce.

Cryptosporidiosis is an unpleasant diarrheal illness for healthy people. However, for those who are HIV-positive, it can last longer and cause more severe symptoms.

A medication called nitazoxanide (Alinia) is normally prescribed to treat the disease.

Cytomegalovirus

Cytomegalovirus (CMV) is virus most commonly thought of as causing serious eye disease in people with weakened immune systems. It can potentially lead to blindness.

CMV can also lead to illness in other areas of the body, such as the digestive tract and parts of the nervous system.

There are currently no medications to cure CMV. However, several powerful antiviral medications can treat the infection. These include:

• gancliclovir (Zirgan)
• valgancilovir (Valcyte)
•  foscarnet (Foscavir) 
• cidofovir (Vistide)

In people with severely weakened immune systems, these CMV medications often need to be given at significant doses over the long term.

However, the damage from CMV infection may slow with the use of antiretroviral therapy. This can result in the rebuilding of the immune system (as demonstrated by clinically significant rises in CD4 count). Anti-CMV therapy may potentially be changed to easier-to-tolerate suppressive treatments.

Herpes simplex viruses

Herpes simplex virus (HSV) is characterized by sores on the mouth, lips, and genitals. Anyone can get herpes, but people with HIV experience increased frequency and severity of outbreaks.

There is no cure for herpes. However, relatively easy-to-tolerate medications, taken long term, can alleviate symptoms of the virus.

Pneumocystis pneumonia

Pneumocystis pneumonia (PJP) is a fungal pneumonia that can be fatal if it’s not diagnosed and treated early. PJP is treated with antibiotics. The risk of a person with HIV developing PJP rises so high that preventive antibiotic therapy may be used if their CD4 count drops below 200 cells per microliter (cells/µL).

Salmonella septicaemia

Commonly referred to as “food poisoning,” salmonellosis is a bacterial infection of the intestines. The bacteria responsible is most often transmitted via food or water that has been contaminated with feces.

The U.S. Food and Drug Administration (FDA) reports that those with weakened immune systems, such as people living with HIV, have at least a 20 times greater risk of salmonellosis. Salmonellosis can spread into the blood, joints, and organs.

Antibiotics are commonly prescribed to treat this infection.

Toxoplasmosis

Toxoplasmosis is caused by parasites in contaminated food. The disease can also be contracted from cat feces.

The risk of significant disease from toxoplasmosis infection rises substantially once the CD4 count drops below 100 cells/µL. An HIV-positive person should ideally avoid all contact with cat feces or any other source of toxoplasmosis exposure.

People who have severely weakened immune systems (less than or equal to 100 CD4 cells/µL) should receive the same preventive antibiotic therapy as that for PJP.

Toxoplasmosis is treated with antimicrobial medications such as trimethoprim-sulfamethoxazole (Bactrim).

Tuberculosis

Tuberculosis (TB) may seem like a disease from the past, but it’s actually the leading cause of death for individuals who have HIV.

TB is caused by Mycobacterium tuberculosis bacteria and is spread through the air. TB generally affects the lungs and has two forms: latent TB and active TB disease.

Individuals with HIV are more likely to become sick with TB.

The disease is treated over the course of six to nine months with a combination of several medications, including:

• isoniazid (INH)
• rifampin (Rifadin)
• ethambutol (Myambutol)
• pyrazinamide

With treatment, both latent and active TB can be managed, but without treatment, TB can lead to death.

Mycobacterium avium complex (MAC)

Mycobacterium avium complex (MAC) organisms are present in most everyday environments. They rarely cause problems for people with healthy immune systems. For those with weakened immune systems, however, MAC organisms can make their way into the body through the GI system and spread. When the organisms spread, they may lead to MAC disease.

This disease causes symptoms such as fever and diarrhea, but it usually isn’t fatal. It can be treated through antimycobacterials and antiretroviral therapy.

Opportunistic cancers

Invasive cervical cancer

Cervical cancer begins in the cells lining the cervix. The cervix is located between the uterus and vagina. Cervical cancer is known to be caused by the human papillomavirus (HPV). Transmission of this virus is extremely common among all sexually active women. But studies have clearly demonstrated that the risk of contracting HPV rises substantially as HIV progresses.

For this reason, HIV-positive women should undergo regular pelvic exams with Pap tests. Pap tests can detect early cervical cancer.

Cervical cancer is considered invasive when it spreads outside the cervix. Treatment options include surgery, radiation therapy, or chemotherapy.

Kaposi sarcoma

Kaposi sarcoma (KS) is linked to infection by a virus called human herpes virus 8 (HHV-8). It causes cancerous tumors of the body’s connective tissues. Dark, purplish skin lesions are associated with KS.

KS isn’t curable, but its symptoms often improve or resolve completely with antiretroviral therapy. Several other treatments are available for people with KS. These include radiation therapy, intralesional chemotherapy, systemic chemotherapy, and retinoids.

Non-Hodgkin’s lymphoma

Non-Hodgkin’s lymphoma (NHL) is a cancer of lymphocytes, cells that are part of the immune system. Lymphocytes are found throughout the body in such places as the lymph nodes, digestive tract, bone marrow, and spleen.

Various treatments are used for NHL, including chemotherapy, radiation therapy, and stem cell transplants.

Source: https://www.healthline.com/health/hiv-aids/opportunistic-infections