Yuehan Zhang

The prognostic role of sex, race, and human papillomavirus in oropharyngeal and nonoropharyngeal head and neck squamous cell cancer

Human papillomavirus (HPV) is a well‐established prognostic marker for oropharyngeal squamous cell cancer (OPSCC). Because of the limited numbers of women and nonwhites in studies to date, sex and racial/ethnic differences in prognosis have not been well explored. In this study, survival differences were explored by the tumor HPV status among 1) patients with OPSCCs by sex and race and 2) patients with nonoropharyngeal (non‐OP) head and neck squamous cell cancers (HNSCCs).

Sex Differences in Risk Factors and Natural History of Oral Human Papillomavirus Infection

UNLABELLED Oral human papillomavirus genotype 16 (HPV16) infection causes oropharyngeal squamous cell carcinoma (SCC), and the prevalence of oropharyngeal SCC is higher among men than women in the United States. In a cohort study of oral HPV infection among 409 individuals aged 18-25 years, the risk among men but not among women significantly increased as the number of recent (ie, within the prior 3 months) oral sex partners increased (Pinteraction = .05). In contrast, the risk among women but not among men significantly decreased as the lifetime number of vaginal sex partners increased (Pinteraction = .037). Men were also significantly less likely than women to clear oral HPV infection. Our data contribute to understanding sex differences in risk for HPV-positive oropharyngeal SCC. CLINICAL TRIALS REGISTRATION NCT00994019.

Human papillomavirus (HPV) 16 antibodies at diagnosis of HPV-related oropharyngeal cancer and antibody trajectories after treatment

OBJECTIVES Despite the fact that HPV-driven oropharyngeal cancer (HPV-OPC) has relatively low recurrence rates, intensive post-therapy monitoring remains the standard of care. Post-treatment biomarkers are needed to risk stratify HPV-OPC patients for more individualized surveillance intensity and which remain at higher recurrence risk. MATERIALS AND METHODS 115 HPV-OPC patients (ascertained by p16 immunohistochemistry and/or in-situ hybridization) from a multicenter prospective case study (HOTSPOT) had blood collected at diagnosis, and 64 of these also had blood collected at post-treatment follow-up visits for up to two years. Samples were centrally tested for antibodies to the L1, E1, E2, E4, E6, and E7 proteins of HPV16. RESULTS At diagnosis, most HPV-OPC cases were seropositive to HPV16 E6 (85%). In post therapeutic samples, HPV16 antibody level decreased slowly over time, but only 3 (of 51 cases seropositive at enrollment) dropped low enough to be classified as seronegative. At 3years after diagnosis, cumulative risk of recurrence was 10.2% and 0% in HPV16 E6 seropositive and E6 seronegative HPV-OPC cases, respectively (p=0.18). Risk of recurrence was increased, although not statistically significant, in those with higher HPV16 E6 antibody levels at diagnosis (per log antibody level, hazard ratio [HR]=1.81, 95%CI=0.47-6.92). CONCLUSION This study confirms the high seroprevalence of HPV oncogenic antibodies at diagnosis of HPV-OPC. HPV16 E6 antibody levels decrease after treatment, but most cases remain seropositive for up to two years. HPV16 E6 antibody levels at diagnosis did not appear to be a strong predictor of recurrence.

Patient experience and anxiety during and after treatment for an HPV-related oropharyngeal cancer.

OBJECTIVES Diagnosis with an HPV-related oropharyngeal cancer includes unique social issues. However, it is unknown how common these psychosocial issues are for patients and whether they continue after treatment. MATERIALS AND METHODS Patients with pathologically confirmed HPV-positive oropharyngeal cancer (HPV-OPC, n=48) were recruited from two medical centers. Participants completed a computer assisted self interview that explored their psychosocial experiences during and after treatment. We examined responses overall and by age. RESULTS The majority of participants with confirmed HPV-OPC, reported being told that HPV could have (90%) or did cause (77%) their malignancy, but only 52% believed that HPV was the main cause of their OPC. Participants over 65years were less likely than younger participants to report that their doctors told them their tumor was HPV-positive (50% vs 84%, p=0.03). Anxiety that their tumor was HPV-related was a major issue among participants when first diagnosed (93%). However, only 17% still reported anxiety after treatment was complete. While many patients reported that providers discussed the emotional effects of diagnosis and treatment adequately (58%), almost half reported discussing these emotional effects inadequately (24%), or not at all (18%). Further, 18% reported that their families still wondered about some questions that they had never asked. CONCLUSION After treatment, some HPV-OPC patients remain concerned about HPV and have unanswered questions about HPV. Older patients had lower awareness of the role of HPV in their cancer.

Prediction of tumor response to experimental radioimmunotherapy with 90Y in nude mice

PURPOSE To identify those factors that predict variability in tumor response to 90Y-radioimmunotherapy based on measurement of incorporated activity and physical dimensions of individual tumors and to apply the concept of effective dose to radioimmunotherapy. METHODS AND MATERIALS Human colon carcinoma xenografts growing in nude mice were treated with anti-CEA antibodies labeled with 90Y directly or through a bispecific antibody/labeled hapten system. Tumor response was measured as the delay in growth to eight times the treatment volume. Noninvasive activity (based on bremsstrahlung radiation) and dimension measurements were made in these animals at several times after label injection. The following parameters were compared for their ability to predict individual tumor response: (a) injected activity, (b) injected activity times a factor based on average uptake as a function of volume, (c) in vivo activity per volume measured in each animal at a single time, (d) the integral over time of in vivo activity per volume in each animal, and (e) the minimum dose for each animal in a uniformly active ellipsoid whose total activity and dimensions varied over time the same as the tumor. RESULTS AND CONCLUSION After correcting for differences in injected activity, two parameters account for much of the variability in tumor response. One of these is the general trend of larger tumors to take up less activity per volume. Additional variability can be accounted for by the in vivo activity per volume measurements. The minimum dose as introduced here is likely to be useful in estimating the biologically effective dose delivered by each treatment.

Use of Bremsstrahlung radiation to monitor Y-90 tumor and whole body activities during experimental radioimmunotherapy in mice

Background. Large differences in uptake between tumors, even for the same size, frequently observed in clinical and experimental radioimmunotherapy (RAIT), make monitoring of uptake in individual tumors imperative in comparing protocols. 90Y, widely‐used for RAIT, emits no gamma radiation and absorption of the beta particle in tissue makes its detection unsuitable for in vivo monitoring. We tested whether bremsstrahlung radiation, produced when betas are decelerated by nuclei, could be used to monitor tumor uptake.

Human Papillomavirus (HPV) 16 E6 seropositivity is elevated in subjects with oral HPV16 infection

INTRODUCTION Human Papillomavirus (HPV) 16 E6 serum antibodies are common in people with HPV-related oropharyngeal cancers (HPV-OPC), but not the general population. We explored HPV16 seroprevalence in people with and without oral HPV16 infection, the cause of HPV-OPC. METHODS Oral rinse samples were collected semiannually and tested for 36 types of HPV DNA by PCR. HPV16 E6 serum antibodies were tested at the visit of first oral HPV detection in participants with prevalent (n=54), or incident (n=39) oral HPV16 DNA; or at baseline in matched participants with no oral HPV16 DNA (n=155) using multiplex serology assay. Predictors of seropositivity were examined using logistic regression. RESULTS HPV16 E6 seropositivity (7.5% vs 0.7%; p=0.005) but not seropositivity to the other HPV16 antigens, was significantly more common in those with than without oral HPV16 infection. There were only 8 HPV16 E6 seropositive participants, but oral HPV16 DNA remained a strong predictor of E6 seropositivity after adjustment for other risk factors (aOR=14.6 95%CI, 1.7-122.5). Seroprevalence was similar in those with prevalent (7.4%; 4/54), and incident (7.7%; 3/39) oral HPV16 infection (p=1.00). E6 seroprevalence was associated with reduced oral HPV16 clearance, but was not statistically significant (HR=0.65 95% CI, 0.16-2.70). Seropositive participants were primarily male (87.5%), HIV-positive (75.0%; median CD4 cell-count of 840) and had oral HPV16 DNA (87.5%). History of an HPV-related cancer (0/8) or HPV-related anogenital dysplasia (1/8) was rare, and 4 participants had recent screening showing no anogenital dysplasia. DISCUSSION HPV16 E6 seropositivity was higher among people with than without oral HPV16 infection, despite no known anogenital disease in these participants.

Prognostic factors for human papillomavirus-positive and negative oropharyngeal carcinomas

Human papillomavirus (HPV)‐positive and HPV‐negative oropharyngeal squamous cell carcinoma (OPSCC) are distinct disease entities. Prognostic factors specific to each entity have not been adequately explored. Goals for this study were: 1) to determine whether HPV‐positive and HPV‐negative OPSCCs have distinct prognostic factors, and 2) to explore the prognostic significance of sex and race in OPSCC after HPV stratification

Pilot randomized controlled trial of a comprehensive smoking cessation intervention for patients with upper aerodigestive cancer undergoing radiotherapy

Smoking among patients with cancer is associated with poor outcomes, however, smoking cessation interventions have had limited success.