Advanced stage HIV-defining cancers in patients with HIV infection are:
Non-Hodgkin lymphoma (including subtypes Burkitt lymphoma, primary central nervous system (CNS) lymphoma, and immunoblastic lymphoma)
Other cancers that appear to be dramatically increased in incidence or severity in patients with HIV infection include:
Hodgkin lymphoma (especially the mixed cellularity and lymphocyte-depleted subtypes)
Other skin and superficial eye cancers
The rates of other common cancers (eg, lung, head and neck, and cervical carcinomas; hepatomas) are several times higher in patients with HIV infection than in the general population. This finding may reflect, at least in part, greater exposure to the viruses or toxins that cause these cancers: hepatitis B and C for hepatoma; human papillomavirus for cervical, anal, penile, and oropharyngeal carcinoma; and alcohol and tobacco for lung and head and neck carcinoma.
Leiomyosarcoma is a rare complication of HIV infection in children.
In general, ART decreases the risk of progression of advanced HIV-defining cancer.
(See also Human Immunodeficiency Virus (HIV) Infection.)
Non-Hodgkin lymphoma
The incidence of non-Hodgkin lymphoma is approximately 25-fold higher in patients with HIV infection (1). Most cases are B-cell, aggressive, high-grade histologic subtype lymphomas. At diagnosis, extranodal sites are usually involved; they include bone marrow, gastrointestinal tract, and other sites that are unusual in non–HIV-associated non-Hodgkin lymphoma, such as the CNS and body cavities (eg, pleural, pericardial, peritoneal).
Common presentations include rapidly enlarging lymph nodes or extranodal masses and systemic symptoms (eg, weight loss, night sweats, fevers).
Diagnosis of non-Hodgkin lymphoma is by biopsy with histopathologic and immunochemical analysis of tumor cells. Abnormal circulating lymphocytes or unexpected cytopenias suggest involvement of the bone marrow, mandating bone marrow biopsy. Tumor staging may require further testing (eg, cerebrospinal fluid examination, imaging of the chest, abdomen, and other areas) specific to areas where tumors are suspected.
Treatment of non-Hodgkin lymphoma is with various regimens of systemic, multidrug chemotherapy that includes cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (of non-Hodgkin lymphoma is with various regimens of systemic, multidrug chemotherapy that includes cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (2). These medications are combined with IV rituximab (an anti-CD20 monoclonal antibody) and supplemented with antiretroviral therapy (ART), prophylactic antibiotics and antifungals, and hematologic growth factors. ). These medications are combined with IV rituximab (an anti-CD20 monoclonal antibody) and supplemented with antiretroviral therapy (ART), prophylactic antibiotics and antifungals, and hematologic growth factors.Rituximab is indicated only for CD20-positive lymphomas. Therapy may be limited by severe myelosuppression, particularly when combinations of myelosuppressive antitumor or antiretroviral medications are used. Radiation therapy may debulk large tumors and control pain or bleeding.
Poor prognosis is predicted by the following:
CD4 count < 100 cells/mcL
Age > 35 years
Poor functional status
Bone marrow involvement
History of opportunistic infections
High-grade histologic subtype
Primary CNS lymphoma
The incidence of primary CNS lymphoma is markedly increased in patients with HIV infection with a very low CD4 count. CNS lymphomas in patients with HIV infection are frequently associated with Epstein-Barr virus (EBV) infection.
Primary CNS lymphomas consist of intermediate- or high-grade malignant B cells, originating in CNS tissue. These lymphomas do not spread systemically, but the prognosis is poor; median survival is < 6 months.
Presenting symptoms include headache, seizures, neurologic deficits (eg, cranial nerve palsies), and mental status changes.
The diagnosis of primary CNS lymphoma involves brain imaging (advanced MRI, CT) showing ring-enhancing lesions and lumbar punctures for cytology and EBV polymerase chain reaction testing and EBV viral load.
Acute treatment of primary CNS lymphomas requires control of cerebral edema using glucocorticoids (3). Although whole-brain radiation therapy and antitumor chemotherapy with high-dose methotrexate (alone or combination) medications are commonly used, these approaches have not been evaluated in large randomized trials and are supported primarily by observational studies and clinical experience. ART in people with HIV infection is associated with improved outcomes and should be initiated or optimized when not already in place.). Although whole-brain radiation therapy and antitumor chemotherapy with high-dose methotrexate (alone or combination) medications are commonly used, these approaches have not been evaluated in large randomized trials and are supported primarily by observational studies and clinical experience. ART in people with HIV infection is associated with improved outcomes and should be initiated or optimized when not already in place.
Cervical cancer
In women with HIV infection, prevalence of human papillomavirus (HPV) infection is increased, oncogenic subtypes (mainly serotypes 16 and 18) persist, the incidence of cervical intraepithelial neoplasia (CIN) is up to 60%, and the incidence of cervical cancer is increased (4). Cervical cancers, if they occur, are more extensive, are more difficult to cure, and have higher recurrence rates after treatment.
The risk of cervical cancer in women with HIV infection increases with poorly controlled disease, including high viral load, low CD4 count, or an insufficient response to ART.
Management methods for CIN or cervical cancer are not changed by HIV infection (5). Frequent Pap tests are important to monitor for progression of CIN. ART may result in resolution of HPV infection, regression of CIN, and significantly reduce risks of invasive cervical cancer (6).
Squamous cell carcinoma of the anus or vulva
Squamous cell carcinoma of the anus and squamous cell carcinoma of the vulva are caused by the same oncogenic serotypes of HPV as cervical cancers and occur more commonly among patients with HIV infection. The increased incidence of anal and vulvar intraepithelial neoplasia and cancers in these patients appears to be caused by both high-risk behaviors (eg, anal-receptive intercourse) and immunosupression by HIV infection.
Anal dysplasia is common, and squamous cell cancers can be very aggressive.
Treatments include surgical extirpation (if feasible), radiation therapy, and combined chemotherapy with a regimen of mitomycin or cisplatin with the addition of 5-fluorouracil (include surgical extirpation (if feasible), radiation therapy, and combined chemotherapy with a regimen of mitomycin or cisplatin with the addition of 5-fluorouracil (7). Immune checkpoint inhibitors (eg, retifanlimab) may also be used.). Immune checkpoint inhibitors (eg, retifanlimab) may also be used.
This photo shows condylomata (1) and squamous cell invasive cancer (2) caused by persistent human papillomavirus (HPV) infection in a person with HIV infection.
Edward R. Cachay, MD, MAS
References
1. Chen Y, Zhao J, Sun P, et al. Estimates of the global burden of non-Hodgkin lymphoma attributable to HIV: a population attributable modeling study. EClinicalMedicine. 2023;67:102370. Published 2023 Dec 16. doi:10.1016/j.eclinm.2023.102370
2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). B-Cell Lymphomas, version 3.2026. https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf. Accessed April 13, 2026.
3. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Central Nervous System Cancers, version 1.2026. https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf. Accessed April 13, 2026.
4. Stelzle D, Tanaka LF, Lee KK, et al. Estimates of the global burden of cervical cancer associated with HIV [published correction appears in Lancet Glob Health 9(2):e119, 2021]. Lancet Glob Health. 2021;9(2):e161-e169. doi:10.1016/S2214-109X(20)30459-9
5. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Cervical Cancer, version 2.2026. https://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf. Accessed April 13, 2026.
6. Kelly H, Weiss HA, Benavente Y, de Sanjose S, Mayaud P; ART and HPV Review Group. Association of antiretroviral therapy with high-risk human papillomavirus, cervical intraepithelial neoplasia, and invasive cervical cancer in women living with HIV: a systematic review and meta-analysis. Lancet HIV. 2018;5(1):e45-e58. doi:10.1016/S2352-3018(17)30149-2
7. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Anal Carcinoma, version 2.2026. https://www.nccn.org/professionals/physician_gls/pdf/anal.pdf. Accessed April 13, 2026.
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