Medical Director, Infection Prevention, El Camino Hospital, Palo Alto Medical Foundation
SOURCE: Salahuddin S, Cohen O, Wu M, et al. Human immunodeficiency virus is associated with poor overall survival among patients with head and neck cancer. Clin infect Dis 2023;76:1449-1458.
Head and neck squamous cell cancers (SCC) occur with greater frequency in human immunodeficiency virus (HIV)-infected persons. These authors, based at a single academic hospital center in the United States, examined clinical, pathological, and other factors on outcomes in persons diagnosed with head and neck SCC between 2002 and 2018. A total of 48 persons with HIV infection and 2,894 persons without HIV infection were diagnosed with head and neck SCC during this interval. While the percent of those who were male (~75%) and used tobacco (89% HIV-positive vs. 79% non-HIV) were similar, there were large differences in the median age, ethnicity, and proportion co-infected with hepatitis C virus (HCV) between the two groups, as follows. The median age of those with HIV was younger compared to those without HIV (55.5 vs. 62 years), and 42% of those with HIV were white vs. 83% of those without HIV; and 66% of those with HIV were co-infected with HCV (data not available for non-HIV-infected persons).
The stage of cancer at the time of diagnosis was similar for both groups, as was the location of the cancer. For those patients with HIV infection, the median CD4 count at the time of cancer diagnosis was 341 cells/mm3, and 81% were virologically suppressed < 200 copies/mL. The nadir CD4 count during treatment was 270 cells/mm3. More than half (58%) had a history of an acquired immunodeficiency syndrome (AIDS)-defining illness. Predictors of survival were determined using a Cox proportional hazards regression model.
Persons with HIV infection had an overall lower median survival compared with non-HIV-infected persons (34 months vs. 94 months, P < 0.001). Even when accounting for socioeconomic and demographic factors, HIV was an independent predictor of poor survival. Although univariate analysis identified HIV viral load as an independent predictor of poorer survival, there was no association of HIV viral load, CD4 count, or duration of HIV infection on survival in multivariate analysis. While human papillomavirus (HPV)-positive SCC generally has a more favorable prognosis than non-HPV cancers in the general population, the opposite appeared to be true for HIV-positive persons, where those HIV-positive patients with HPV-positive tumors had significantly worse survival. Tumor expression of CD8 was significantly lower in HIV-positive persons with HPV-positive tumors compared with the non-HIV-positive cohort.
Survival rates were worse even in those with earlier stage cancers; the three-year survival among early stage cancer patients was 50% vs. 79.8% for HIV-positive vs. non-HIV patients (P = 0.04).
HIV-infected patients develop head and neck cancers at 1.5 to 4 times the rate of the general population and have much poorer overall survival, even with a similar presentation and similar treatment, and despite generally being younger than their non-HIV-infected peers. This group of HIV-infected persons with head and neck cancer generally had well-controlled HIV infection, and most had CD4 counts > 200 cells/mm3, even during treatment. Either their history of HIV/AIDS or current HIV infection negatively affected the biology of these tumors and/or their response to therapy. This study raises questions about the biology of these tumors and interactions with HIV/HCV, but also about whether treatment for early stage head and neck cancers in HIV-positive persons should be re-examined.
SOURCE: Pandey K, Fairley CK, Chen MY, et al. Changes in the syphilis rapid plasma reagin titer between diagnosis and treatment. Clin Infect Dis 2023;76:795-799.
Rapid plasma reagin (RPR) titers may be more dynamic than previously recognized, which could affect interpretation of response to therapy. Based on retrospective data from a large Australian health service, which provides free sexually transmitted disease (STD) and human immunodeficiency virus (HIV) testing and care, RPR titers in persons ≥ 16 years of age collected between 2011 and 2020 were analyzed. Serologic testing for syphilis was done using an RPR test (Becton Dickinson), a Treponema pallidum particle agglutination assay, and either an enzyme-linked immunoabsorbent assay (Trepanostika EIA, BioMerieux) (before January 2016) or a chemiluminescent immunoassay (LIAISON, Diasorin) after January 2016. A total of 96,158 persons had at least one syphilis test performed during this time period. Of these, 766 cases had a repeat titer performed within 14 days of their initial presentation and before they were treated. Of these, 121 had primary syphilis, 100 had secondary syphilis, 339 had early latent infection, 31 had late latent infection, and 175 were unclassified. The median RPR titer at the time of presentation was 1:32.
Of these 766 cases, 14.8% had a ≥ four-fold change in their RPR titer within 14 days of presentation in the absence of treatment (83.2% of these had increased titers and 16.8% had decreased titers). These fluctuating titers were distributed fairly evenly across syphilis stage, including 18% of those with primary infection, 19% of those with secondary infection , 15.6% of those with early latent disease, and 10.8% of those unclassified. Changes in RPR titer were more pronounced with an increasing interval since initial testing: Within one to three days of the initial RPR testing, 5.8% had a change in RPR titers of ≥ four-fold. By comparison, 26.2% had a change in their RPR ≥ four-fold if repeat testing occurred 10-14 days later. As a result, of those 59 cases with repeat titers within two weeks, and who also had follow-up testing post-treatment a median of 271 days later, five cases (8.4%) would have been classified as having an insufficient response to therapy if the initial titer but not their subsequent titer was used.
These authors observed fluctuations in syphilis RPR titers ≥ four-fold within two weeks of initial testing, in the absence of treatment, in 14.8% of persons. If treatment was delayed by 10-14 days, the potential for ≥ four-fold fluctuation in the RPR titer increased to 26%.
I have always thought of RPR titers as fairly stable, especially in persons with longer-standing infection. But these data suggest that persons with primary, secondary, and even early latent infection can have what we would consider clinically significant changes in their titer in advance of treatment, which might affect the interpretation of their response to therapy. The greater the number of days between testing and treatment, the more likely the change in the titer. Since patients often are called back for treatment, these data suggest that a repeat RPR should be obtained at the time they return for treatment, effectively establishing a new baseline.
