The Current Burden of Oropharyngeal Cancer: A Global Assessment Based on GLOBOCAN 2020.

BACKGROUND: Oropharyngeal cancer (OPC) is a complex disease whose etiologies, either related to risk factors such as smoking or alcohol, or linked to HPV infection, are believed to be responsible for wide gender and geographical variability. This study depicts the current burden of OPC worldwide. METHODS: Estimated OPC new cases, deaths, age-standardized rates (ASR) for both incidence and mortality in 2020 were obtained from the GLOBOCAN database for each country and across 20 UN-defined world regions by sex. The incidence-to-mortality ratio (IMR) was also estimated from ASR. RESULTS: Worldwide, 98,400 new cases and 48,100 OPC deaths were estimated in 2020, with ASR of 1.1 and 0.51 per 100,000 for incidence and mortality, respectively. ASR for both incidence and mortality were approximately four times higher in men and varied greatly across geographical regions and countries within the same region. Higher incidence was estimated in Europe, North-America, Australia, and New Zealand. Mortality was the highest in Central-East Europe, Western Europe, Melanesia, South-Central Asia, and the Caribbean. South-Central Asia, most African areas, and Central America exhibited the lowest IMR values, whereas North-America, Australia, New Zealand, and North-Europe had the highest. CONCLUSIONS: The marked geographical and gender variability in OPC incidence and mortality is likely to reflect the distribution of risk factors and the diverse prevalence of HPV-negative and HPV-positive cases. IMPACT: Findings are likely to drive future research, support the development of targeted strategies to counteract disease burden, establish priorities for prevention and treatment programs, and address inequality in access to services.

Leukoplakia, Oral Cavity Cancer Risk, and Cancer Survival in the U.S. Elderly.

Screening for oral leukoplakia, an oral cavity cancer (OCC) precursor, could lead to earlier detection of OCC. However, the progression rate from leukoplakia to OCC and the benefits of leukoplakia screening for improving OCC outcomes are currently unclear. We conducted a case-cohort study of U.S. adults ages ≥65 years in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linkage. We identified leukoplakia diagnoses through Medicare claims, and OCC diagnoses through SEER cancer registries. Weighted Cox regression was used to estimate leukoplakia associations with OCC incidence, and the absolute OCC risk following leukoplakia diagnosis was calculated. Among OCC cases, we compared OCC stage and OCC survival between cases with a prior leukoplakia diagnosis versus those without prior leukoplakia. Among 470,266 individuals in the SEER-Medicare subcohort, 1,526 (0.3%) had a leukoplakia diagnosis. Among people with leukoplakia, the cumulative OCC incidence was 0.7% at 3 months and 2.5% at 5 years. OCC risk was most increased <3 months after leukoplakia diagnosis (HR, 115), likely representing the diagnosis of prevalent cancers. Nonetheless, risk remained substantially increased in subsequent follow-up [HR ≥ 3 months, 24; 95% confidence interval (CI), 22-27; HR ≥ 12 months, 22, 95% CI, 20-25]. Among OCC cases (N = 8,927), those with prior leukoplakia were less likely to be diagnosed at regional/distant stage (OR, 0.36; 95% CI, 0.30-0.43), and had lower mortality (HR, 0.74; 95% CI, 0.65-0.84) when compared with OCC cases without a prior leukoplakia. Individuals with leukoplakia have substantially elevated risk of OCC. Lower stage and better survival after OCC diagnosis suggest that leukoplakia identification can lead to earlier OCC detection and reduced mortality.

HPV-associated Oropharyngeal Cancers--Are They Preventable?

It is not known whether a human papillomavirus (HPV)-induced oropharyngeal precancerous lesion could be identified by screening with a pap test equivalent or whether one even exists. In this issue of the journal (beginning on page 1378), Fakhry and colleagues report their results showing that cytologic evaluation of the oropharynx, although useful in detecting invasive oropharyngeal cancers, may have limited utility as a screening modality for detecting precancer. These findings argue against the potential for secondary prevention of HPV-associated oropharyngeal cancers through screening for and preventing the progression of precancer and highlight the opportunity for primary prevention through prophylactic HPV vaccination, if proven efficacious and cost-effective.

Cancer burden in the HIV-infected population in the United States.

BACKGROUND: Effective antiretroviral therapy has reduced the risk of AIDS and dramatically prolonged the survival of HIV-infected people in the United States. Consequently, an increasing number of HIV-infected people are at risk of non-AIDS-defining cancers that typically occur at older ages. We estimated the annual number of cancers in the HIV-infected population, both with and without AIDS, in the United States. METHODS: Incidence rates for individual cancer types were obtained from the HIV/AIDS Cancer Match Study by linking 15 HIV and cancer registries in the United States. Estimated counts of the US HIV-infected and AIDS populations were obtained from Centers for Disease Control and Prevention surveillance data. We obtained estimated counts of AIDS-defining (ie, Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer) and non-AIDS-defining cancers in the US AIDS population during 1991-2005 by multiplying cancer incidence rates and AIDS population counts, stratified by year, age, sex, race and ethnicity, transmission category, and AIDS-relative time. We tested trends in counts and standardized incidence rates using linear regression models. We multiplied overall cancer rates and HIV-only (HIV infected, without AIDS) population counts, available from 34 US states during 2004-2007, to estimate cancers in the HIV-only population. All statistical tests were two-sided. RESULTS: The US AIDS population expanded fourfold from 1991 to 2005 (96,179 to 413,080) largely because of an increase in the number of people aged 40 years or older. During 1991-2005, an estimated 79 656 cancers occurred in the AIDS population. From 1991-1995 to 2001-2005, the estimated number of AIDS-defining cancers decreased by greater than threefold (34,587 to 10,325 cancers; P(trend) < .001), whereas non-AIDS-defining cancers increased by approximately threefold (3193 to 10,059 cancers; P(trend) < .001). From 1991-1995 to 2001-2005, estimated counts increased for anal (206 to 1564 cancers), liver (116 to 583 cancers), prostate (87 to 759 cancers), and lung cancers (875 to 1882 cancers), and Hodgkin lymphoma (426 to 897 cancers). In the HIV-only population in 34 US states, an estimated 2191 non-AIDS-defining cancers occurred during 2004-2007, including 454 lung, 166 breast, and 154 anal cancers. CONCLUSIONS: 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.

Assessment of human papillomavirus in lung tumor tissue.

BACKGROUND: Lung cancer kills more than 1 million people worldwide each year. Whereas several human papillomavirus (HPV)-associated cancers have been identified, the role of HPV in lung carcinogenesis remains controversial. METHODS: We selected 450 lung cancer patients from an Italian population-based case-control study, the Environment and Genetics in Lung Cancer Etiology. These patients were selected from those with an adequate number of unstained tissue sections and included all those who had never smoked and a random sample of the remaining patients. We used real-time polymerase chain reaction (PCR) to test specimens from these patients for HPV DNA, specifically for E6 gene sequences from HPV16 and E7 gene sequences from HPV18. We also tested a subset of 92 specimens from all never-smokers and a random selection of smokers for additional HPV types by a PCR-based test for at least 54 mucosal HPV genotypes. DNA was extracted from ethanol- or formalin-fixed paraffin-embedded tumor tissue under strict PCR clean conditions. The prevalence of HPV in tumor tissue was investigated. RESULTS: Specimens from 399 of 450 patients had adequate DNA for analysis. Most patients were current (220 patients or 48.9%) smokers, and 92 patients (20.4%) were women. When HPV16 and HPV18 type-specific primers were used, two specimens were positive for HPV16 at low copy number but were negative on additional type-specific HPV16 testing. Neither these specimens nor the others examined for a broad range of HPV types were positive for any HPV type. CONCLUSIONS: When DNA contamination was avoided and state-of-the-art highly sensitive HPV DNA detection assays were used, we found no evidence that HPV was associated with lung cancer in a representative Western population. Our results provide the strongest evidence to date to rule out a role for HPV in lung carcinogenesis in Western populations.

Beyond cervical cancer: burden of other HPV-related cancers among men and women.

Human papillomavirus (HPV) infection is a necessary cause of cervical cancer, and is etiologically associated with a subset of cancers of the anus, oropharynx, penis, vagina, and vulva. Current data indicate that HPV infection is potentially associated with 90%-93% of anal cancers, 12%-63% of oropharyngeal cancers, 36%-40% of penile cancers, 40%-64% of vaginal cancers, and 40%-51% of vulvar cancers. HPV infection accounts for up to 492,800 cervical cancers and 97,215 cases of noncervical HPV-related cancers worldwide during 2002, including up to 50,780 cancers among men (13,485 anal cancers, 26,775 oropharyngeal cancers, and 10,520 penile cancers) and up to 46,435 cancers among women (14,787 anal cancers, 6,048 oropharyngeal cancers, and 25,600 vaginal/vulvar cancers). In the United States annually (1998-2003), up to 10,846 cervical cancers, 4,753 noncervical cancers among men, and 4,128 noncervical cancers among women are potentially attributable to HPV infection. Incidence rates for cervical cancer have declined significantly during the past 30 years in the United States, consistent with the success of Pap smear screening. However, incidence rates for anal, oropharyngeal, and vulvar cancers have increased substantially in recent years. The high proportion of cervical and noncervical cancers caused by HPV types 16 and 18, that is, 70%-76% for cervical cancers and 63%-95% for noncervical cancers, underscores the potential for prevention of a majority of cervical as well as noncervical HPV-related cancers through prophylactic HPV vaccination.