HPV persistence is necessary for the development of anogenital cancer. Studies show that cervical and anal HPV infections in women and in men who have sex with men are common. Clearance of HPV infection is similarly common; few individuals show persistence unless they are HIV-infected. HIV strongly influences the development of cervical and anal cancer, as well as their pre-malignant counterparts. Women with cervical and vulvar HPV-associated lesions have higher rates of anal cancer than the general population. HPV also plays an important role in pathogenesis of head and neck cancers, particularly oropharyngeal cancer. Two commercially available HPV vaccines have been proven to be safe and efficacious against cervical HPV16/18 infections and associated precancerous lesions; one of these has also been shown to prevent HPV16/18-associated anal lesions. The FDA has also just approved a new nonavalent HPV vaccine. HPV vaccines will play an important role in prevention of HPV-associated cancers.

Until recently, primary central nervous system lymphoma (PCNSL) was associated with a uniformly dismal prognosis. It is now reasonable to anticipate long-term survival and possibly cure for a significant proportion of patients diagnosed with PCNSL. Accumulated data generated over the past 10 years has provided evidence that long-term progression-free survival (PFS) can reproducibly be attained in a significant fraction of PCNSL patients that receive dose-intensive chemotherapy consolidation, without whole brain radiotherapy. One consolidative regimen that has reproducibly demonstrated promise is the combination of infusional etoposide plus high-dose cytarabine (EA), administered in first complete remission after methotrexate, temozolomide and rituximab-based induction. Given evolving principles of management and the mounting evidence for reproducible improvements in survival rates in prospective clinical series, our goal in this review is to highlight and update principles in diagnosis, staging and management as well as to review data regarding the pathogenesis of central nervous system lymphomas, information that is likely to constitute a basis for the implementation of novel therapies that are requisite for further progress in this unique phenotype of non-Hodgkin lymphoma.

Anal cancer is an increasingly common non-AIDS-defining cancer among individuals infected with the human immunodeficiency virus (HIV). It is associated with human papillomavirus (HPV). HPV16 is the most common genotype detected in anal cancers. The HPV types detected in anal cancer are included in the 9-valent vaccine. HPV vaccines have demonstrated efficacy in reducing anal precancerous lesions in HIV-infected individuals. Standard treatment has been fluorouracil and mitomycin (or cisplatin) plus radiation. Continued studies are needed to test new treatment strategies in HIV-infected patients with anal cancer to determine which treatment protocols provide the best therapeutic index.

With the advent of effective combination antiretroviral therapy, HIV infection has been transformed from a fatal disease to a chronic condition. There is renewed clinical interest in long-term morbidities, including malignancies that occur disproportionately within this population. Non-AIDS-defining cancers (NADCs) are a significant source of morbidity and mortality in the aging HIV-infected population. There are data to suggest that incidence rates are elevated among HIV-infected individuals for many cancer sites, particularly those with a confirmed or suspected infectious etiology. The complex interplay between behavioral risk factors, coexistence of viral infections, immunodeficiency and antiretroviral therapy makes it difficult to analyze why certain cancers develop more frequently in HIV-infected individuals. The challenge to clinicians caring for HIV-infected patients is to develop and implement effective means to screen, treat, and prevent NADCs in the future. This review presents data on whether NADCs are increased in the HIV-Infected population, as well as ongoing research on epidemiology, prevention and pathogenesis of this evolving aspect of the HIV epidemic.

Objective

Determine the COVID-19 seroconversion rate for patients with multiple myeloma receiving a COVID-19 vaccine.

Materials and methods

After 45 patients received their second COVID-19 vaccine dose, their serum IgG antibodies were measured: 22 with monoclonal gammopathy (MG) of unknown significance, 3 with smoldering myeloma, 2 with light chain amyloidosis, and 18 with MG (9 in remission, 6 out of remission, and 3 with free light-chain gammopathy alone). A second serum specimen was retained for 16 patients with MG. Their antibody levels were compared to those of 78 uninfected healthy vaccinated control patients.

Results

Three patients with MG had low antibody levels on blood collected 98, 100, and 113 days after the initial vaccine dose (2 with MG of unknown significance and 1 with hypogammaglobulemia). The other 40 patients with MG (seroconversion rate 93%) and both patients with amyloidosis produced antibodies. Relative to days after vaccination, patients with MG had lower antibody levels than control patients.

Conclusion

After receiving a COVID-19 vaccine, most patients with MG produce anti-SARS-CoV-2 antibodies comparable to levels in uninfected vaccinated healthy control patients.

Background

Anal squamous cell carcinoma (ASCC) is uncommon, yet seen more frequently in the setting of the human immunodeficiency virus (HIV). Chemoradiotherapy is the definitive modality of treatment for patients with ASCC; this study examines factors impacting clinical outcomes in a large cohort of HIV-positive and HIV-negative patients.

Methods

A retrospective review was conducted of patients treated for nonmetastatic ASCC at a single institution between 2005 and 2018. Freedom from local recurrence (FFLR), freedom from distant metastasis, and overall survival (OS) were calculated using the Kaplan-Meier method, and univariate and multivariate analysis were performed using the Cox proportional hazards model.

Results

During the study period, 111 patients initiated definitive treatment for ASCC. Median age of the entire cohort was 56.7 years (interquartile range, 51.5-63.5), with 52 patients (46.8%) being HIV-positive. At median follow-up of 28.0 months, the 2- and 5-year FFLR were 78.2% (95% confidence interval [CI], 70.4-87.0) and 74.6% (95% CI, 65.8-84.5), respectively. Multivariate analysis revealed time from diagnosis to treatment initiation (median, 8 weeks; hazard ratio, 1.06; 95% CI, 1.03-1.10) to be significantly associated with worse FFLR and OS. HIV-positive patients had a trend toward worse FFLR (log-ranked p = .06). For HIV-positive patients with post-treatment CD4 less than 150 cells per mm³ , there was significantly worse OS (log-ranked p = .015).

Conclusion

A trend toward worse FFLR was seen in HIV-positive patients, despite similar baseline disease characteristics as HIV-negative patients. Worse FFLR and OS was significantly associated with increased time from diagnosis to treatment initiation. Poorer OS was seen in HIV-positive patients with a post-treatment CD4 count less than 150 cells per mm³ .

Implications for practice

Human immunodeficiency virus (HIV)-positive patients with anal squamous cell carcinoma can represent a difficult clinical scenario. Definitive radiation with concurrent chemotherapy is highly effective but can result in significant toxicity and a decrease in CD4 count that could predispose to HIV-related complications. As HIV-positive patients have largely been excluded from prospective clinical trials, this study seeks to provide greater understanding of their outcomes with radiation therapy, potential predictors of worse local control and overall survival, and those most at risk after completion of treatment.

Objective

Anal cancer is an uncommon malignancy with the primary treatment for localized disease being concurrent radiation and chemotherapy. Pre-treatment PET/CT is useful for target delineation, with minimal exploration of its use in prognostication. In the post-treatment setting there is growing evidence for advanced PET metrics in assessment of treatment response, and early identification of recurrence essential for successful salvage, however this data is limited to small series.

Methods

Patient with non-metastatic anal cancer from a single institution were retrospectively reviewed for receipt of pre- and post-treatment PET/CTs. PET data was co-registered with radiation therapy planning CT scans for precise longitudinal assessment of advanced PET metrics including SUVmax, metabolic tumor volume (MTV), and total lesion glycolysis (TLG), for assessment with treatment outcomes. Treatment outcomes included local recurrence (LR), progression free survival (PFS), and overall survival (OS), as defined from the completed radiation therapy to the time of the event. Cox proportional hazard modeling with inverse probability weighting (IPW) using the propensity score based on age, BMI, T-stage, and radiation therapy dose were utilized for assessment of these metrics.

Results

From 2008 to 2017 there were 72 patients who had pre-treatment PET/CT, 61 (85%) had a single follow up PET/CT, and 35 (49%) had two follow up PET/CTs. The median clinical follow-up time was 25 months (IQR: 13-52) with a median imaging follow up time of 16 months (IQR: 7-29). On pre-treatment PET/CT higher MTV2.5 and TLG were significantly associated with higher risk of local recurrence (HR 1.11, 95% CI: 1.06-1.16, p<0.001; and HR 1.12, 95% CI: 1.05-1.19, p<0.001), and worse PFS (HR 1.09, 95% CI: 1.04-1.13, p<0.001; and HR 1.09, 95% CI: 1.03-1.12, p = 0.003) and OS (HR 1.09, 95% CI: 1.04-1.16, p = 0.001; and HR 1.11, 95% CI: 1.04-1.20, p = 0.004). IPW-adjusted pre-treatment PET/CT showed higher MTV2.5 (HR 1.09, 95% CI: 1.02-1.17, p = 0.012) and TLG (HR 1.10, 95% CI: 1.00-1.20, p = 0.048) were significantly associated with worse PFS, and post-treatment MTV2.5 was borderline significant (HR 1.16, 95% CI: 1.00-1.35, p = 0.052).

Conclusion

Advanced PET metrics, including higher MTV2.5 and TLG, in the pre-treatment and post-treatment setting are significantly associated with elevated rates of local recurrence, and worse PFS and OS. This adds to the growing body of literature that PET/CT for patient with ASCC should be considered for prognostication, and additionally is a useful tool for consideration of early salvage or clinical trial of adjuvant therapies.

Objective

This study compared the mutation profile and tumor mutational burden (TMB) in women with HIV (WWH) diagnosed with lung adenocarcinoma (n = 8) or breast ductal neoplasm (n = 13) who were enrolled into the Women's Interagency HIV Study (WIHS).

Design

Previous studies tended to focus on single institutions based on sample availability. This study is based on a representative, multicenter cohort that represents the racial and ethnic composition of women with HIV in the United States.

Methods

The study sequenced the complete human exome of n = 26 cancer samples from HIV-positive women, using Ion torrent next-generation sequencing. The study cohort was compared with a HIV-negative cohort obtained from the Genomic Data Commons Data Portal of the NCI.

Results

There were no differences in known cancer mutations between breast cancer and lung cancer that developed in WWH and those that developed in HIV-negative (HIV-) women; however, WWH presented a significantly higher TMB in comparison to HIV- patients. Seventy-five percent of lung cancers and 61% of breast cancers were defined as TMB-high (more than 10 mutation/mb of DNA).

Conclusion

This study affirms the recommendation that WWH be included in clinical trials of novel treatments for these cancers. Although these data are preliminary, the high TMB in WLHV suggests, paradoxically, that this immune challenged population may benefit greatly from immune checkpoint inhibitor therapies.

Anti-CD30 therapy for Hodgkin lymphoma led to transient loss of detectable CD4+ T-cell HIV RNA and a decrease in residual plasma viremia. Targeting nonviral markers expressed on HIV-1 transcriptionally active cells may lead to reduced measures of HIV-1 persistence.

In people living with HIV (PLWH) on antiretroviral therapy (ART), virus persists in a latent form where there is minimal transcription or protein expression. Latently infected cells are a major barrier to curing HIV. Increasing HIV transcription and viral production in latently infected cells could facilitate immune recognition and reduce the pool of infected cells that persist on ART. Given that programmed cell death protein 1 (PD-1) expressing CD4⁺ T cells are preferentially infected with HIV in PLWH on ART, we aimed to determine whether administration of antibodies targeting PD-1 would reverse HIV latency in vivo. We therefore evaluated the impact of intravenous administration of pembrolizumab every 3 weeks on HIV latency in 32 PLWH and cancer on ART. After the first infusion of anti-PD-1, we observed a median 1.32-fold increase in unspliced HIV RNA and 1.61-fold increase in unspliced RNA:DNA ratio in sorted blood CD4⁺ T cells compared to baseline. We also observed a 1.65-fold increase in plasma HIV RNA. The frequency of CD4⁺ T cells with inducible virus evaluated using the tat/rev limiting dilution assay was higher after 6 cycles compared to baseline. Phylogenetic analyses of HIV env sequences in a participant who developed low concentrations of HIV viremia after 6 cycles of pembrolizumab did not demonstrate clonal expansion of HIV-infected cells. These data are consistent with anti-PD-1 being able to reverse HIV latency in vivo and support the rationale for combining anti-PD-1 with other interventions to reduce the HIV reservoir.