What are the most common HIV‑associated malignancies, their recommended screening, and standard treatment approaches?

HIV-Related Malignancies: Common Types, Screening, and Treatment

People living with HIV should be co-managed by an oncologist and HIV specialist, with antiretroviral therapy (ART) continued throughout cancer treatment, and cancer treatment should follow standard guidelines without modifications based solely on HIV status. 1

AIDS-Defining Malignancies

Kaposi Sarcoma (KS)

• Represents 12% of all cancers in people living with HIV (PLWH) and remains significantly elevated despite 90% risk reduction with ART 1
• Caused by HHV-8 (human herpesvirus 8) infection in the setting of persistent immunosuppression 1
• ART is the backbone of treatment for KS, particularly for symptomatic disease 1
• Critical pitfall: Monitor for immune reconstitution inflammatory syndrome (IRIS), which can be life-threatening when initiating ART 1

Non-Hodgkin Lymphoma (NHL)

• Most common HIV-associated malignancy at 21% of all cancers in PLWH 1
• Includes aggressive B-cell malignancies, with approximately 40% being EBV-associated 2
• Primary central nervous system lymphomas are 80-100% EBV-positive 2
• Primary effusion lymphoma (PEL) is specifically associated with KSHV and occurs with profound immunosuppression 2

Cervical Cancer

• Risk elevated 3- to 5-fold in women living with HIV compared to general population 1
• Caused by persistent high-risk HPV infection 1
• Represents only 1% of cancers in PLWH in the United States due to screening programs and predominantly male HIV population 1
• Treatment follows NCCN Guidelines for Cervical Cancer, including concurrent chemotherapy with definitive radiation 1
• Important consideration: Women with cervical cancer/CIN should be evaluated for multifocal HPV disease including anal and vulvar cancer 1
• Higher recurrence rates after loop excision due to more frequent endocervical extension 1

Non-AIDS-Defining Malignancies

Lung Cancer

• Most common non-AIDS-defining cancer at 11% of all cancers in PLWH 1
• Risk is 2- to 5-fold higher than HIV-negative population 1
• Screening follows standard NCCN Guidelines for Lung Cancer Screening with no HIV-specific modifications currently 1
• Smoking cessation is critical given high prevalence of tobacco use in this population 1
• Treatment parallels NCCN Guidelines for Non-Small Cell Lung Cancer 1

Anal Cancer

• Represents 10% of cancers in PLWH 1
• Risk is 25- to 35-fold higher than general population 1
• Associated with persistent anal HPV infection 1
• Screening approach: Many HIV specialists screen with anal cytology, high-resolution anoscopy, and annual digital rectal exam, though no national consensus exists 1
• If high-grade anal intraepithelial neoplasia (AIN) identified, perform high-resolution anoscopy 1
• Treatment of dysplasia: Electrocautery (ablation) superior to topical therapy (fluorouracil, imiquimod), though recurrence rates remain high 1
• Cancer treatment follows NCCN Guidelines for Anal Carcinoma 1
• Enhanced surveillance required: Anoscopy every 3-6 months for 3 years post-treatment 1
• Critical consideration: Women with anal cancer should have colposcopic examination for multifocal HPV disease (vulvar, vaginal, cervical) 1

Hodgkin Lymphoma (HL)

• Risk is 5- to 14-fold higher than general population, representing 4% of cancers in PLWH 1
• Nearly 90% of cases are EBV-associated in HIV-positive patients 1
• Presents with more advanced disease, including B symptoms and bone marrow involvement 1
• Critical pitfall: B symptoms should prompt workup for opportunistic infection, especially if CD4 count is low 1
• Standard treatment is ABVD regimen (doxorubicin, bleomycin, vinblastine, dacarbazine) 1
• Dose reductions may be required for prolonged severe neutropenia 1
• Growth factors indicated for low CD4 counts with prolonged neutropenia 1
• PET/CT-guided therapy may be challenging due to confounders (enlarged/metabolically active nodes from infection, HIV viremia) 1
• Autologous stem cell transplant is safe and effective for recurrent/relapsed disease 1
• Prophylaxis required: Consider antibiotics for gram-negative bacteria and Pneumocystis jirovecii pneumonia if CD4 <200 cells/mcL 1

Other Significant Malignancies

• Prostate cancer: 7% 1
• Liver cancer: 5% (associated with hepatitis B/C coinfection) 1
• Colorectal cancer: 5% 1

Critical Management Principles

HIV Management During Cancer Therapy

• ART must be continued throughout cancer treatment, though modifications may be necessary 1
• Consult both HIV and oncology pharmacists for drug-drug interactions between ART and chemotherapy 1
• Poor performance status may be from HIV, cancer, or other causes—determine etiology as ART may improve HIV-related poor performance 1

Lymphadenopathy Evaluation

• Always consider non-malignant causes (opportunistic infections) in PLWH 1
• Biopsy suspicious/PET-avid nodes more liberally to rule out infectious etiology versus metastatic disease 1

Underlying Risk Factors

• Oncogenic viral coinfections (HPV, HHV-8, hepatitis B/C, EBV) drive many malignancies 1
• Higher prevalence of carcinogen exposure (tobacco, heavy alcohol) contributes to cancer risk 1
• Immune dysregulation persists even with effective ART 1