A B S T R A C T PurposeRecent increases in incidence and survival of oropharyngeal cancers in the United States have been attributed to human papillomavirus (HPV) infection, but empirical evidence is lacking. Patients and MethodsHPV status was determined for all 271 oropharyngeal cancers collected by the three population-based cancer registries in the Surveillance, Epidemiology, and End Results (SEER) Residual Tissue Repositories Program by using polymerase chain reaction and genotyping (Inno-LiPA), HPV16 viral load, and HPV16 mRNA expression. Trends in HPV prevalence across four calendar periods were estimated by using logistic regression. Observed HPV prevalence was reweighted to all oropharyngeal cancers within the cancer registries to account for nonrandom selection and to calculate incidence trends. Survival of HPV-positive and HPV-negative patients was compared by using Kaplan-Meier and multivariable Cox regression analyses. ResultsHPV prevalence in oropharyngeal cancers significantly increased over calendar time regardless of HPV detection assay (P trend Ͻ .05). For example, HPV prevalence by Inno-LiPA increased from 16.3% during 1984 to 1989 to 71.7% during 2000 to 2004. Median survival was significantly longer for HPV-positive than for HPV-negative patients (131 v 20 months; log-rank P Ͻ .001; adjusted hazard ratio, 0.31; 95% CI, 0.21 to 0.46). Survival significantly increased across calendar periods for HPV-positive (P ϭ .003) but not for HPV-negative patients (P ϭ .18). Population-level incidence of HPV-positive oropharyngeal cancers increased by 225% (95% CI, 208% to 242%) from 1988 to 2004 (from 0.8 per 100,000 to 2.6 per 100,000), and incidence for HPV-negative cancers declined by 50% (95% CI, 47% to 53%; from 2.0 per 100,000 to 1.0 per 100,000). If recent incidence trends continue, the annual number of HPV-positive oropharyngeal cancers is expected to surpass the annual number of cervical cancers by the year 2020. ConclusionIncreases in the population-level incidence and survival of oropharyngeal cancers in the United States since 1984 are caused by HPV infection.

The proportion of OSCCs that are potentially HPV-related increased in the United States from 1973 to 2004, perhaps as a result of changing sexual behaviors. Recent improvements in survival with radiotherapy may be due in part to a shift in the etiology of OSCCs.

Context Solid organ transplant recipients have elevated cancer risk due to immunosuppression and oncogenic viral infections. Since most prior research has concerned kidney recipients, large studies that include recipients of differing organs can inform cancer etiology. Objective Describe the overall pattern of cancer among solid organ transplant recipients. Design Cohort study using linked data from the U.S. Scientific Registry of Transplant Recipients (1987–2008) and 13 state/regional cancer registries. Participants and Setting Solid organ transplant recipients in the U.S. Main Outcome Measure Standardized incidence ratios (SIRs) and excess absolute risks (EARs) assessing relative and absolute cancer risk in transplant recipients compared to the general population. Results Registry linkages yielded data on 175,732 solid organ transplants (58.4% kidney, 21.6% liver, 10.0% heart, 4.0% lung). Overall cancer risk was elevated (N=10,656 cases, incidence 1374.7 per 100,000 person-years; SIR 2.10, 95%CI 2.06–2.14; EAR 719.3, 95%CI 693.3–745.6, per 100,000 person-years). Risk was increased (p<0.001) for 32 different malignancies, some related to known infections (e.g., anal cancer, Kaposi sarcoma) and others unrelated (e.g., melanoma, thyroid and lip cancers). The most common malignancies with elevated risk were non-Hodgkin lymphoma (N=1504, incidence 194.0; SIR 7.54, 95%CI 7.17–7.93; EAR 168.3, 95%CI 158.6–178.4) and cancers of the lung (N=1344, incidence 173.4; SIR 1.97, 95%CI 1.86–2.08; EAR 85.3, 95%CI 76.2–94.8), liver (N=930, incidence 120.0; SIR 11.56, 95%CI 10.83–12.33; EAR 109.6, 95%CI 102.0–117.6), and kidney (N=752, incidence 97.0; SIR 4.65, 95%CI 4.32–4.99; EAR 76.1, 95%CI 69.3–83.3). Lung cancer risk was most elevated in lung recipients (SIR 6.13, 95%CI 5.18–7.21) but also increased among other recipients (SIR 1.46, 95%CI 1.34–1.59 for kidney; 1.95, 1.74–2.19 for liver; 2.67, 2.40–2.95 for heart). Liver cancer was elevated only among liver recipients (SIR 43.83, 95%CI 40.90–46.91), who manifested exceptional risk in the first 6 months (SIR 508.97, 95%CI 474.16–545.66) and continuing two-fold excess for 10–15 years (SIR 2.22, 95%CI 1.57–3.04). Among kidney recipients, kidney cancer was elevated (SIR 6.66, 95%CI 6.12–7.23) and bimodal in onset. Kidney cancer was also increased in liver and heart recipients (SIR 1.80, 95%CI 1.40–2.29, and 2.90, 2.32–3.59, respectively). Conclusions Recipients of a kidney, liver, heart, or lung transplant have an increased risk for diverse infection-related and unrelated cancers, compared with the general population.

Dramatic declines in KS and NHL were temporally related to improving therapies, especially introduction of HAART, but those with AIDS remain at marked risk. Among non-AIDS-related cancers, a recent increase in Hodgkin lymphoma was observed.

Over a 15-year period (1991-2005), increases in non-AIDS-defining cancers were mainly driven by growth and aging of the AIDS population. This growing burden requires targeted cancer prevention and treatment strategies.

Data are limited regarding cancer risk in human immunodeficiency virus (HIV)‐infected persons with modest immunosuppression, before the onset of acquired immunodeficiency syndrome (AIDS). For some cancers, risk may be affected by highly active antiretroviral therapy (HAART) widely available since 1996. We linked HIV/AIDS and cancer registries in Colorado, Florida and New Jersey. Standardized incidence ratios (SIRs) compared cancer risk in HIV‐infected persons (initially AIDS‐free) during the 5‐year period after registration with the general population. Poisson regression was used to compare incidence across subgroups, adjusting for demographic factors. Among 57,350 HIV‐infected persons registered during 1991–2002 (median CD4 count 491 cells/mm3), 871 cancers occurred during follow‐up. Risk was elevated for Kaposi sarcoma (KS, SIR 1,300 [n = 173 cases]), non‐Hodgkin lymphoma (NHL, 7.3 [n = 203]), cervical cancer (2.9 [n = 28]) and several non‐AIDS‐defining malignancies, including Hodgkin lymphoma (5.6 [n = 36]) and cancers of the lung (2.6 [n = 109]) and liver (2.7 [n = 14]). KS and NHL incidence declined over time but nonetheless remained elevated in 1996–2002. Incidence increased in 1996–2002 compared to 1991–1995 for Hodgkin lymphoma (relative risk 2.7, 95%CI 1.0–7.1) and liver cancer (relative risk infinite, one‐sided 95%CI 1.1‐infinity). Non‐AIDS‐defining cancers comprised 31.4% of cancers in 1991–1995, versus 58.0% in 1996–2002. For KS and NHL, risk was inversely related to CD4 count, but these associations attenuated after 1996. We conclude that KS and NHL incidence declined markedly in recent years, likely reflecting HAART‐related improvements in immunity, while incidence of some non‐AIDS‐defining cancers increased. These trends have led to a shift in the spectrum of cancer among HIV‐infected persons. © 2008 Wiley‐Liss, Inc.

Although occurring in overall excess, most non-AIDS-defining cancers do not appear to be influenced by the advancing immunosuppression associated with HIV disease progression. Some cancers that met our criteria for potential association with immunosuppression may have occurred in excess in persons with HIV/AIDS because of heavy smoking (lung cancer), frequent exposure to human papillomavirus (penile cancer), or inaccurately recorded cases of Kaposi sarcoma (soft tissue malignancies) in these persons. However, Hodgkin disease, notably of the mixed cellularity and lymphocytic depletion subtypes, and possibly lip cancer and testicular seminoma may be genuinely influenced by immunosuppression.

Risk of HPV-associated cancers was elevated among persons with AIDS and increased with increasing immunosuppression. The increasing incidence for anal cancer during 1996-2004 indicates that prolonged survival may be associated with increased risk of certain HPV-associated cancers.