Background and Objective: Nasopharyngeal carcinoma (NPC) is a tumor of the head and neck that arises from the mucosal epithelium of the nasopharynx. Epstein-Barr virus (EBV) is a human herpes virus and the necessary cause for NPC. The 5-year survival rate for NPC patients is higher when diagnosed at an earlier stage of disease. Therefore, NPC screening should be prioritized for early detection. The objective of this narrative review is to synthesize the existing literature from the past decade describing evaluations of EBV-based serological markers for NPC screening. Methods: We performed a literature search in PubMed for studies published from 2010 to 2020. Studies were required to be English-language articles. Twelve articles fulfilled all inclusion criteria, including eight studies conducted among the general population in southeastern China, three studies in genetically high-risk Taiwanese families, and one study comparing EBV serology versus circulating EBV DNA for NPC prediction. Key Content and Findings: Studies suggest that EBV-based serology has the potential to be an effective tool to aid in early detection of NPC. The synthesized research also collectively suggests that incorporation of antibody against multiple EBV targets, as well as efforts to optimize assay output, can improve the ability of EBV serological markers to detect NPC. Finally, recent data from the only randomized trial provide preliminary evidence that screening using anti-EBV immunoglobulin A (IgA) antibody may achieve the goal of reducing mortality from NPC. Conclusions: Late diagnosis is one of the reasons for poor survival after an NPC diagnosis. In high-risk areas, early diagnosis aided by EBV antibody could therefore improve survival.

Oral human papillomavirus (HPV) is associated with increasing rates of HPV‐associated oropharyngeal cancer (OPC) in men. Sequential infection from one site to another has been demonstrated at the cervix and anus. Thus, risk of an oral HPV infection after a genital infection of the same type in the HPV infection in men study was investigated. Samples from 3140 men enrolled in a longitudinal cohort were assessed for sequential genital to oral infection with one of nine HPV types (HPV 6, 11, 16, 18, 31, 33, 45, 52 and 58); and then also sequential, same‐type oral to genital infection. Incidence rate ratios (IRRs) compared rates of oral HPV among men with and without prior genital infection of the same type. Risk of sequential HPV infections were assessed using Cox proportional hazards model. Incidence of an oral HPV infection was significantly higher among men with a prior genital infection of the same type for any of the 9 HPV types (IRR: 2.3; 95% CI: 1.7‐3.0). Hazard ratio of a sequential genital to oral HPV infection was 2.3 (95% CI: 1.7‐3.1) and 3.5 (95% CI: 1.9‐6.4) for oral to genital infection. Both changed minimally after adjustment for age, country, circumcision, alcohol use, lifetime sexual partners and recent oral sex partners. HPV infections at one site could elevate risk of a subsequent genital or oral HPV infection of the same type in men, emphasizing the importance of vaccination to prevent all HPV infections.

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HPV-related oropharyngeal cancer (OPC) incidence is increasing among men. Biomarkers that can identify oral HPV 16/18 infections likely to persist, the obligate precursor for HPV-OPC, are needed. Control of oral co-infections, including Epstein-Barr virus (EBV), could serve as a biomarker of immune competence and the ability to control oral HPV. We assessed the association between oral EBV and oral HPV 16/18 persistence among 63 men in the HIM Study who tested HPV16/18 positive. Detection of oral EBV was significantly associated with oral HPV 16/18 ≥ 12-month persistence and deserves evaluation as a biomarker for oral HPV persistence and related OPC.

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Background HPV causes oral warts and oropharyngeal cancer (OPC). HPV-attributable OPC incidence among men is significantly increasing worldwide yet few studies have reported oral HPV across multiple countries or examined factors associated with low and high-risk HPV separately. Methods Oral gargles from 3,095 men in the multinational HPV Infection in Men (HIM) Study were HPV genotyped. Multivariable models assessed factors independently associated with high-risk and low-risk HPV prevalence. Results The prevalence of high-risk and low-risk HPV was 6.0% and 2.8% respectively. Greater number of sexual partners was only associated with high-risk HPV (1.88; 95% CI: 1.22, 2.90) prevalence. In multi-variable models, residing in Mexico (1.66, 95% CI: 1.15, 2.40) and smoking (1.66, 95% CI: 1.13, 2.44) were significantly associated with high-risk HPV, and history of consistent gum bleeding (2.16; 95% CI: 1.35, 3.45) was significantly associated with low-risk HPV. Gender of the sexual partner did not alter the results for either high- or low-risk HPV endpoints. Conclusions Different factors were independently associated with high- and low-risk oral HPV. Oral sexual behaviors were associated with high-risk HPV and oral health with low-risk HPV. High risk HPV prevalence differed by country of residence, highlighting the need for additional studies in multiple countries.

Elevated cancer-specific mortality in PWH has been demonstrated for non-AIDS-defining malignancies. However, additional clinical endpoints of interest, including patient-reported outcomes (PROs), have not been systematically examined in PWH and cancer. We evaluated differences in patient-reported symptomology between cancer patients with versus without HIV using data from 12,529 patients at the Moffitt Cancer Center, including 55 with HIV. The symptoms were assessed using the Edmonton Symptom Assessment Scale (ESAS), which asks patients to rank 12 symptoms on a scale of 1–10, with scores ≥7 considered severe. The responses across all questions were summed to create a composite score. Vital status through t July 2021 was determined through linkage to the electronic health record. PWH reported a higher composite ESAS score on average (44.4) compared to HIV-uninfected cancer patients (30.7, p-value < 0.01). In zero-inflated negative binomial regression models adjusted for cancer site, sex, and race, the composite ESAS scores and the count of severe symptoms were 1.41 times (95% CI: 1.13–1.77) and 1.45 times (95% CI: 1.09–1.93) higher, respectively, in cancer patients with HIV. Among PWH, higher ESAS scores were associated with mortality (p-value = 0.02). This is the first demonstration of uniquely poor PROs in PWH and cancer and suggests that patient symptom monitoring to improve clinical endpoints deserves further study.

Background Rates of oropharyngeal cancer (OPC) associated with alcohol & tobacco use have decreased, while human papillomavirus (HPV) associated OPC has increased among men in the US. Secretory leukocyte protease inhibitor (SLPI), detectable in a variety of secretions, has been implicated in cancers of the head and neck, associated with tumor progression and anti-viral activity. Using the recently verified oral gargle specimen, this study aimed to assess the association of salivary SLPI expression with risk of OPC and response to treatment. Methods A case-control study design compared levels of salivary SLPI among OPC cases to age and tobacco smoking matched healthy controls. Oral HPV DNA and SLPI was quantified from oral gargle specimens. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for associations of oral SLPI and risk of OPC and treatment outcomes. Results In crude and adjusted analyses of 96 OPC cases and 97 age- and smoking-matched controls, OPC was not significantly associated with oral gargle SLPI levels. Among cases, oral SLPI was associated with tonsillectomy (p = 0.018) and among controls oral SLPI was associated with HPV in the oral gargle (p = 0.008). Higher concentrations of SLPI was significantly associated with increased odds of incomplete treatment response (T2: OR: 12.39; 95% CI: 1.44–106.72; T3: OR: 9.86; 95% CI: 1.13–85.90) among all cases, but not among P16+ cases. Conclusions Salivary SLPI was not associated with OPC risk but was associated with higher odds of an incomplete treatment response.