Induction of HIV-1-specific mucosal immune responses following intramuscular recombinant adenovirus serotype 26 HIV-1 vaccination of humans.

BACKGROUND: Defining mucosal immune responses and inflammation to candidate human immunodeficiency virus type 1 (HIV-1) vaccines represents a current research priority for the HIV-1 vaccine field. In particular, it is unclear whether intramuscular immunization can elicit immune responses at mucosal surfaces in humans. METHODS: In this double-blind, randomized, placebo-controlled clinical trial, we evaluated systemic and mucosal immune responses to a candidate adenovirus serotype 26 (Ad26) vectored HIV-1 envelop (Env) vaccine in baseline Ad26-seronegative and Ad26-seropositive healthy volunteers. Systematic mucosal sampling with rectal Weck-Cel sponges and rectal biopsies were performed. RESULTS: Intramuscular immunization elicited both systemic and mucosal Env-specific humoral and cellular immune responses in the majority of subjects. Individuals with preexisting Ad26-specific neutralizing antibodies had vaccine-elicited immune responses comparable to those of subjects who were Ad26 seronegative. We also observed no increase in activated total or vector-specific mucosal CD4+ T lymphocytes following vaccination by either histopathology or flow cytometry. CONCLUSIONS: These data demonstrate that a single intramuscular administration of this Ad26-vectored HIV-1 Env vaccine elicited both systemic and mucosal immune responses in humans. Induction of antigen-specific humoral and cellular mucosal immunity was not accompanied by a detectable increase in mucosal inflammation. CLINICAL TRIALS REGISTRATION: NCT01103687.

Challenges in Management of Squamous Cell Carcinoma of the Anus in New England and Across the United States: A Review of the National Cancer Data Base.

BACKGROUND: Management of squamous cell carcinoma of the anus (SCCA) is becoming more relevant, as its incidence continues to increase. The purpose of this study was to evaluate regional and national data to assess trends in epidemiology, access to cancer center care, and overall management strategies in SCCA. STUDY DESIGN: A review of available data from the American College of Surgeons Committee on Cancer National Cancer Data Base focused on incidence, sex, age, stage at diagnosis, distance traveled for care, and utilization of therapy as first course of treatment (FCT). The analysis included 40,817 patients treated for SCCA at 1513 cancer centers in the United States, of which 2347 patients were treated at 109 cancer centers in New England, between the years 2003 and 2013. RESULTS: Over the 11-year period, incidence of SCCA increased by 76% in the United States and by 83.8% in New England. Stage was unknown in 11.7% of all US cases, significantly higher than more common cancers, for example, breast (4.3%), prostate (6%), or colon (7.8%) (P<0.001). Patients in southern New England, compared with northern New England, traveled <10 miles more often (53.4% vs. 38.1%) (P<0.001), and>25 miles less often (14.3% vs. 28.7%) (P<0.001). Cases of early stage SCCA (0, I) were more frequent in southern New England (29.2%) than northern New England (21.7%) (P=0.0025), whereas more advanced stage (II to IV) cases occurred less frequently in southern New England (60.1%) than northern New England (72%) (P<0.001). Overall, the most common FCT was chemoradiotherapy, utilized in 49.3% of cases, followed by chemoradiotherapy plus surgery in 19.4% of cases. Stage unknown patients were treated with chemoradiotherapy in 34.6% of cases, with surgery alone in 20.2%, and with chemoradiotherapy plus surgery in 15.4% of cases. CONCLUSIONS: The incidence of SCCA is steadily increasing. Its frequency of stage unknown is significantly higher than other common cancer sites. Travel distance and stage at diagnosis data may reflect regional differences in cancer center care access. Although chemoradiotherapy remains the most commonly utilized FCT, challenges in accurate staging and inconsistent use of additional prognostic variables may affect optimal treatment.