HIV & Cancer Risk: Expert Interview

Although rates of AIDS-defining malignancies have declined in recent decades, cancer remains a leading cause of mortality in people living with HIV (PLWHIV). A significant portion of this patient population has begun to reach advanced age and non-AIDS-defining cancers have become more prevalent and now account for nearly one-fourth of all deaths among people with HIV.¹

Higher rates of non-AIDS-related cancers, including lung and hepatocellular cancers, have been observed in patients with HIV compared with the general population.¹ In addition, increased cancer-specific mortality rates have been found in people with HIV compared with individuals without HIV for several common malignancies: breast cancer (hazard ratio [HR] 2.64; 95% CI, 1.86-3.73), melanoma (HR 1.93; 95% CI, 1.14-3.27), colon cancers (HR 1.40; 95% CI, 1.09-1.80), and lung cancer (HR 1.28; 95% CI, 1.14-1.44).²

Despite these elevated risks, the rate of cancer screening is low in this population. Of note, the rate of vaccination against common oncogenic viruses, which represent the cause of cancer in nearly 40% of people with HIV, is also suboptimal, according to a paper published in the World Journal of Clinical Oncology.¹ This demonstrates a “pressing need to educate patients and healthcare professionals about the importance of cancer preventive measures in these vulnerable patients,” the study authors wrote.

In an effort to alleviate this miseducation, the study authors made/reiterated the following recommendations:

• Hepatitis B virus (HBV) vaccination for all seronegative patients with HIV, with repeat doses until anti­HBs titers ≥10 to 100 IU/mL are achieved. In those with low CD4 count and high HIV viral load, double doses may be considered.
• Human papilloma virus (HPV) vaccination for PLWHIV aged <26 years and <40 years old for men who have sex with men (MSM). When available, 3 doses of 9-valent vaccine are recommended.
• Education about the risks of smoking and assistance with smoking cessation, as the prevalence of both lung cancer and smoking is high in this population.
• Cancer screening schedules similar to those recommended for the general population. No studies have yet examined such schedules for PLWHIV:

– Mammography every 1 to 3 years in women aged 50 to 70 years

– In those aged >50 years with life expectancy >10 years, measurement of prostate specific antigen every 2 to 4 years and annual fecal occult blood test and sigmoidoscopy every 5 years or colonoscopy every 10 years

– “In patients with cirrhosis and in those with HBV coinfection and either a history of elevated transaminases or risk factors for [hepatocellular carcinoma (HCC)] (family history of HCC, Asians, Africans), abdominal ultrasound and measurement of alpha­fetoprotein levels are recommended every 6 mo[nths] to enable the early diagnosis of HCC.”¹

• For AIDS-defining cancers, the study authors recommended liquid­based cervical cytology test every 1 to 3 years in women aged >21 years or within 1 year following first sexual encounter, digital rectal examination with or without anal cytology in MSM and those with HPV ­associated dysplasia, and thorough skin evaluation at regular intervals “to detect cancers such as Kaposi’s sarcoma, basal cell carcinoma, and malignant melanoma.”¹

Infectious Disease Advisor interviewed the following experts to gain additional insights regarding cancer risk and prevention in HIV: renowned HIV pioneer Paul A. Volberding, MD, professor of Medicine at the University of California, San Francisco, director of the UCSF AIDS Research Institute and director of research for UCSF Global Health Sciences, and principal investigator and co-director of the NIAID-funded UCSF-Gladstone Center for AIDS Research; and Carlos D. Malvestutto, MD, MPH, medical director of the Family AIDS Clinic and Education Services program at Nationwide Children’s Hospital, and assistant professor of Infectious Diseases at the Ohio State University Wexner Medical Center.

Infectious Disease Advisor: Why are cancer screening and vaccination rates so low among patients with HIV, and what can be done to increase these rates?

Dr Volberding: When talking about HIV in this context, 2 of the groups that are most vulnerable to infection are gay men and people who inject drugs, and these can be further stratified by race and ethnicity. The individuals most in need of access to care are those who are marginalized because of sexual orientation, race, and drug use. Many of the issues pertaining to access to care stem from stigmatization — due to being gay, for example, especially in African American communities.

For female patients, there is [a greater] incentive to vaccinate against HPV because of the risk for cervical cancer. HPV is not as relevant [for] gay men with HIV because this is an aging population, and many of these patients have already been exposed and infected. I think the main issue in terms of HIV and HPV is that we should be doing early vaccinations across patient demographics, as statistically some of these boys may become gay men — so ideally, we can protect this high-risk population early. Much of the focus on HPV vaccination should really be addressed in adolescence. If you don’t vaccinate until well after the sexual debut, it is likely too late.

Regarding HBV, vaccines are quite effective, and it’s a shame that not everyone is vaccinated. Many gay men have already been exposed and are immune to it, and thus are not at increased risk for liver cancer. But not everyone becomes immune — there are people who haven’t been exposed or who have chronic HBV infection, so it’s still important to screen in this population. There will likely be new therapies for HBV in the near future.

Hepatitis C virus (HCV) is another cause of liver cancer that is very treatable, so patients should also be screened for this infection.

Dr Malvestutto: People living with HIV are at significantly higher risk for certain types of cancer, particularly HIV-associated or AIDS-defining malignancies such as Kaposi sarcoma, B-cell non-Hodgkin lymphoma, and cervical cancer. However, they are also at increased risk for non-AIDS associated malignancies such as anal cancer (19-fold higher risk compared with people who do not have HIV), Hodgkin lymphoma (8-fold higher risk), oropharyngeal cancer (2-fold higher risk), and hepatocellular carcinoma (2-fold higher risk).³ 

As the life expectancy of PLWHIV has increased, cancer has become a leading cause of death. In the case of anal cancer, cervical cancer, and most oropharyngeal cancers, this is because of the increased risk for chronic coinfection with high-risk HPV strains. PLWHIV are also at increased risk for cervical and anal premalignant high-grade squamous intraepithelial lesions.

Although HPV vaccination rates in Ryan White-funded HIV clinics have improved, the efficacy of the 9-valent HPV vaccine at inducing antibody production for the high-risk strains of HPV decreases to about 85% in patients with CD4 counts <200 cells/mL. Thus, providers may choose to delay HPV vaccination until patients’ CD4 counts have increased to >200 cells/mL.

Further, until November 2018, HPV vaccination was only approved for patients aged <26 years, so PLWHIV aged >26 years would not qualify for HPV vaccination. The ACTG study A5298 showed that HPV vaccination for PLWHIV aged >27 years did not prevent new anal HPV infections or improve outcomes for HPV-associated anal lesions categorized as high-grade squamous intraepithelial lesions.⁴  

However, the study showed that there may be a benefit in prevention of oral HPV infections when HPV vaccination was offered to PLWHIV aged >27 years. Now that the 9-valent HPV vaccine has received approval by the US Food and Drug Administration for patients up to age 45 years, it should be possible to ensure that all patients are vaccinated.

Anal cancer screening programs have been developed following the model of cervical cancer screening programs and including anal Pap tests and colposcopy. The HIV primary care guidelines recommend anal Pap smears for MSM, women with a history of receptive anal intercourse or abnormal cervical Pap test results, and all patients with HIV with genital warts (weak recommendation, moderate quality evidence). However, the actual risk-benefit of treatment of anal high-grade squamous epithelial lesions is currently being assessed by a very large National Institutes of Health-sponsored randomized trial, ANCHOR (Anal Cancer HSIL Outcomes Research).

Regarding liver cancer risk, there is a high prevalence of coinfection with HBV and HCV in PLWHIV. For patients with chronic HCV, there are now very effective, well-tolerated treatment regimens available that make it possible to cure the virus in >95% of patients. Patients at risk for liver cancer coinfected with HCV should be offered treatment as soon as possible. Patients with chronic HBV are placed on HIV antiretroviral therapy (ART) regimens that include drugs to suppress HBV. These measures can greatly reduce the risk for hepatocellular carcinoma.

For PLWHIV who are uninfected with HCV, screening for HCV is recommened, frequently — at least once a year — and those uninfected with HBV who are not immune should be offered vaccination. The problem with HBV vaccination is that the vaccine is not very immunogenic for patients with lower CD4 counts, so providers have the option of repeating the vaccine series, adopting a 4-dose series rather than the standard 3-dose series, or increasing the concentration of vaccine used to improve antibody production and protection.