Cancer is one of the leading causes of death among people living with HIV in Brazil. However, with antiretroviral therapy (ART), the cancer profile has shifted: Kaposi sarcoma and AIDS-related lymphomas have declined, whereas cancers such as anal, liver, oropharyngeal, and lung cancers now predominate and may occur at higher rates and at younger ages in this population.

“Non-AIDS-defining cancers have become the main problem,” said Ivan França, MD, PhD, head of the Division of the Infectious Diseases at A.C. Camargo Cancer Center, an oncology hospital in São Paulo, Brazil. “Even with suppressed viral load, the risk accumulates over time and demands ongoing surveillance.”

A study that followed more than 87,000 people living with HIV in the state of São Paulo showed a 79-fold higher risk for anal cancer and a 26-fold higher risk for Hodgkin lymphoma than in the general population, along with significant increases in liver and oropharyngeal cancer risk.

Brazil, however, does not have a national protocol specific to screening and management of non-AIDS-defining cancers in people living with HIV. The Brazilian Ministry of Health’s Clinical Protocol and Therapeutic Guidelines for the Management of HIV Infection in Adults, last updated in 2024, explicitly acknowledges this gap and advises that cancer screening should follow the guidelines for the general population, with individualized adaptations.

The only formal exception is cervical cancer. Guidelines from the Brazilian National Cancer Institute specifically recommend that women living with HIV undergo annual Pap tests, rather than the 3-year interval recommended for the general population. For all other cancers — anal, lung, liver, and lymphomas — there is no standardized national guidance.

This gap contrasts with the international landscape. In the past 2 years, three important guidelines addressing cancer screening in people living with HIV have been published or updated:

• The European AIDS Clinical Society (EACS) updated its guidelines in October 2024 with detailed recommendations on screening for anal cancer, cervical cancer, hepatocellular carcinoma, and other cancers in this population.
• The International Anal Neoplasia Society (IANS) published, in January 2024, the first international consensus on anal cancer screening, with guidance for high-risk groups, including people living with HIV.
• The US National Institutes of Health (NIH), together with the CDC, issued federal guidance in July 2024 recommending access to high-resolution anoscopy for anal cancer screening in people living with HIV.

In the absence of a national protocol, these international guidelines provide the strongest scientific foundation currently available to guide clinical practice in Brazil.

Drivers of Elevated Cancer Risk

Three main factors explain why cancer risk remains elevated even when HIV is well controlled with ART.

• Hepatitis and human papillomavirus (HPV) risks. HPV infection is more prevalent and persistent in people living with HIV, increasing the risk for anal and cervical cancer. Hepatitis B and C, which are also more common in this population, substantially increase the risk for hepatocellular carcinoma. Epstein-Barr virus has been linked to lymphomas more common in this population. Even with ART controlling HIV, these coinfections retain oncogenic potential.
• Earlier age at diagnosis. Several cancers — anal cancer, lymphomas, and hepatocellular carcinoma — tend to appear at younger ages in people living with HIV than in the general population. This means screening strategies based only on traditional age ranges may miss early neoplasms in this group.
• Higher prevalence of smoking. Smoking is consistently more common among people living with HIV than in the general population, contributing to increased lung cancer risk independent of viral control. In clinical practice, smoking cessation becomes a priority preventive intervention rather than a generic recommendation.

“For these patients, quitting smoking is likely the single most impactful preventive intervention we have today,” França said. “It’s technically simple but requires an active, structured, and continuous approach.”

Global Guidance on Screening

Cervical Cancer

There is national and international consensus on the need for intensified screening of women living with HIV. INCA recommends an annual Pap test, starting soon after the onset of sexual activity. The EACS also reaffirms this recommendation because of the higher risk for persistent HPV infection and faster progression of precursor lesions.

The principle is clear: Longer screening intervals appropriate for the general population are insufficient for people living with HIV. The risk is not only failing to detect an initial lesion but also losing patients to follow-up over time.

Anal Cancer

Anal cancer shows the largest relative increase in risk among people living with HIV — about 79 times higher in the São Paulo study — and is the area where international guidance has advanced most rapidly.

IANS recommends beginning screening at age 35 for people living with HIV, regardless of other risk factors. When results are normal, annual anal cytology is preferred. If cytology detects abnormalities, high-resolution anoscopy — which allows visualization and biopsy of precursor lesions — is the next step.

The NIH and CDC guidance published in July 2024 goes further, recommending that people living with HIV should have access to structured screening programs that include high-resolution anoscopy, especially those at very high risk, such as men who have sex with men. The document notes, however, that access to high-resolution anoscopy is limited even in the US, and implementation depends on provider training and adequate infrastructure.

EACS takes a more pragmatic stance: It recommends an annual clinical exam with visual inspection and a digital rectal exam for everyone, reserving anal cytology and high-resolution anoscopy for settings where these resources are available.

There is no absolute consensus on the optimal anal screening strategy — whether cytology followed by high-resolution anoscopy for everyone or clinical surveillance with selective use of diagnostic procedures. What is broadly agreed upon is that people living with HIV carry an elevated cancer risk and deserve some form of systematic surveillance.

“Screening only makes sense when there is a realistic possibility of diagnostic confirmation and treatment,” said Marcio Nucci, MD, head of Infection in Hematology and Cell Therapy at Grupo Oncoclínicas, one of Brazil’s largest oncology networks. “Identifying a lesion without access to high-resolution anoscopy, biopsy, and appropriate treatment does not reduce mortality.”

Hepatocellular Carcinoma

Surveillance for hepatocellular carcinoma in people living with HIV does not differ substantially from that for the general population, but coinfection with hepatitis B or C is more common and accelerates progression to fibrosis and cirrhosis.

EACS recommends surveillance every 6 months with abdominal ultrasound and alpha-fetoprotein testing for all patients with cirrhosis or advanced fibrosis (F3 or F4), regardless of cause. The same recommendation applies to patients with hepatitis B who do not have cirrhosis if they have a family history of hepatocellular carcinoma or are of African ancestry.

The central point is not to create a different surveillance protocol but to ensure coinfections are diagnosed, treated, and monitored appropriately. Effective treatment of viral hepatitis drastically reduces the risk for cancer progression among people with HIV.

Lymphomas

There is no structured screening for lymphomas, but clinical vigilance must be rigorous. EACS and the NIH stress that persistent lymphadenopathy that lasts more than 4 weeks, or asymmetric or progressive lymph node enlargement, should prompt investigation with biopsy, even in patients with suppressed viral load and preserved CD4 counts.

Constitutional symptoms — such as prolonged unexplained fever, drenching night sweats, and unintentional weight loss — require active investigation. Overlooking these signs in younger patients remains a major cause of diagnostic delay.

Lung Cancer

For lung cancer, international guidelines recommend applying the same criteria used for the general population — that is, annual low-dose CT for people aged 50-80 years with a smoking history of 20 pack-years or more. The difference is prevalence: Because smoking is more common among people living with HIV, a larger proportion of this population will qualify for screening.

EACS emphasizes that smoking cessation should be addressed at every visit, with structured treatment offered — behavioral therapy and pharmacotherapy — rather than isolated counseling.

Vaccination for Cancer Prevention

Two vaccines have a proven direct impact on cancer in people living with HIV.

• HPV vaccine. Available through the Brazilian Unified Health System for people living with HIV aged 9-45 years, with a three-dose schedule. Vaccination prevents not only genital warts and precursor lesions but also directly reduces the risk for cervical, anal, vulvar, vaginal, penile, and oropharyngeal cancers. The EACS recommends vaccination for all eligible individuals regardless of prior HPV exposure because the vaccine can protect against viral types not yet acquired.
• Hepatitis B vaccine. Recommended for all nonimmune individuals. People living with HIV may have a reduced immune response to the vaccine, especially with low CD4 counts, and may require higher-dose regimens or additional booster doses.

“For people living with HIV, vaccination is not just infection prevention; it is cancer prevention,” França said. “HPV and hepatitis B are clear examples of how well‑executed vaccine policies change long‑term cancer outcomes.”

Treatment Principles and Challenges

When cancer develops, treatment indications should follow those used for the general population. “Stage at diagnosis has become the main determinant of outcome,” Nucci said. “With sustained viral suppression and immune recovery, response rates, toxicity profiles, and cancer-specific survival are similar to the general population for many cancers.”

HIV status alone should not exclude patients from surgery, chemotherapy, radiotherapy, immunotherapy, or targeted therapies. These treatments can be offered according to standard protocols.

EACS outlines two guiding principles for cancer management in this population:

• Continuation of ART. ART should be maintained whenever possible during cancer treatment. Interrupting ART raises the risk for viral rebound, CD4 decline, and opportunistic infections — complications that can compromise both safety and cancer treatment efficacy.
• Management of drug interactions. Several antiretrovirals share metabolic pathways with chemotherapeutic agents, especially protease inhibitors and integrase inhibitors. This can lead to toxic chemotherapy levels or, conversely, subtherapeutic levels that undermine antitumor efficacy. EACS recommends a systematic review of all potential interactions before initiating chemotherapy, with ART regimen adjustments as needed. Regimens based on integrase inhibitors, such as dolutegravir or bictegravir, tend to have fewer drug interactions than protease inhibitor-based regimens.

“Systematic review of interactions is not a technical detail; it is part of treatment safety,” Nucci emphasized. Therefore, coordination between infectious disease and oncology teams is essential, not optional, in these cases.

From Guidelines to Practice

We now have robust knowledge about the increased cancer risk in people with HIV, detailed international guidelines, and available screening technologies. The Brazilian Unified Health System has a huge strategic advantage: It already monitors these people throughout their lives, França said. What’s missing is not patient contact but integrating cancer screening into the routine of that care.

The absence of a national protocol means cancer screening for people living with HIV today depends more on the initiative of the individual clinician than on a structured program. That creates major inequalities: People followed at reference centers may receive adequate surveillance, while those relying solely on primary care often do not.

Incorporating cancer screening into routine care for more than 1 million Brazilians living with HIV is not a technical impossibility — international guidelines indicate the way. As Nucci concluded, “The evidence is already there; the impact depends on turning guidelines into continuous care.”

Daniela Barros is a journalist with postgraduate training in social journalism from the Pontifical Catholic University of São Paulo, São Paulo, Brazil. She is a special student in the Department of Social Medicine at the Ribeirão Preto Medical School in Ribeirão Preto, Brazil. She has been involved in medicine for 23 years and has contributed to several specialized publications.

This story was translated from Medscape’s Portuguese edition.