Cancer Type and Histology Influence Cutaneous Immunotherapy Toxicities: A Multi-Institutional Cohort Study.

BACKGROUND: Cutaneous immune-related adverse events (cirAEs) are the most common toxicities to occur in the setting of immune checkpoint inhibitor (ICI) therapy. Identifying patients who are at increased risk of developing cirAEs may improve quality of life and outcomes. OBJECTIVE: To investigate the influence of cancer type and histology on the development of cirAEs in the setting of ICI therapy and survival outcomes. METHODS: This retrospective cohort study included patients between December 1, 2011, and October 30, 2020. They received ICIs from 2011-2020 with follow-up of outcomes through October 2021. We identified 3,668 ICI recipients who were seen at Mass General Brigham and Dana-Farber. Of these, 669 developed cirAEs. Records that were incomplete or categories of insufficient sample size were excluded from the study cohort. Multivariate Cox proportional hazards models were utilized to investigate the impact of cancer organ system and histology on cirAE development, after adjusting for demographics, Charlson Comorbidity Index, ICI type, cancer stage at ICI initiation, and year of ICI initiation. Time-varying Cox proportional hazards modeling was utilized to examine the impact of cirAE development on mortality. RESULTS: Compared to other non-epithelial cancers (neuroendocrine, leukemia, lymphoma, myeloma, sarcoma, and central nervous system malignancies), cutaneous squamous cell carcinoma (cSCC) (HR = 3.57, p < 0.001), melanoma (HR = 2.09, p < 0.001), head and neck adenocarcinoma (HR = 2.13, p = 0.009), genitourinary transitional cell carcinoma (HR = 2.15, p < 0.001), and genitourinary adenocarcinoma (HR = 1.53, p = 0.037) were at significantly higher risk of cirAEs in multivariate analyses. The increased risk of cirAEs translated into an adjusted survival benefit for melanoma (HR = 0.37, p < 0.001) and cSCC (HR = 0.51, p = 0.011). CONCLUSIONS: The highest rate of cirAEs and subsequent survival benefits were observed in cutaneous malignancies treated with ICIs. This study improves our understanding of patients who are at highest risk of developing cirAEs and would, therefore, benefit from appropriate counseling and closer monitoring by their oncologists and dermatologists throughout their ICI therapy. Limitations include its retrospective nature and cohort from one geography.

HPV infection and breast cancer risk: insights from a nationwide population study in Taiwan.

Background: The prevalence of cancer, specifically breast cancer, has raised globally. The etiology of breast cancer has been attributed to age, genetic mutations, reproductive history, hormone therapy, lifestyle factors, and viral infections. The human papillomavirus (HPV) has been one of the most widespread sexually transmitted infection in the United States. The role of HPV in breast oncogenesis was hypothesized before, yet the association remained unclear. Methods: In this study, we employed a nationwide population study using centralized patient data managed by the Ministry of Health and Welfare in Taiwan and the Taiwan Cancer Registry database. The breast cancer incidence rates of the 467,454 HPV patients were compared to twice as many non-HPV patients with matching sex and age. Cumulative breast cancer incidence rates were presented by a Kaplan-Meier curve, and the relative risk of breast cancer for HPV and non-HPV patients were calculated using Cox-regression model. Results: Our results indicated a crude hazard ratio (HR) and an adjusted hazard ratio (aHR) of 2.336 and 2.271, respectively, when comparing the risk of breast cancer in the HPV and non-HPV group. The risk of breast cancer was comparable or higher than those of head and neck cancer (aHR=1.595) and cervical cancer (aHR=2.225), which both were found to have causal relationships with HPV. The Kaplan-Meier curve further illustrated a higher cumulative risk across 84 months for HPV patients (p<.0001). Besides HPV, age (p<.0001), insurance providers (p<.001), and comorbidities such as abnormal liver function (aHR=1.191, p=.0069) and hyperlipidemia (aHR=1.218, p=.0002) were found to be correlated with higher risks of breast cancer. Conclusion: A correlation between HPV and breast cancer can be inferred using national health databases. More molecular studies are required to understand the mechanism of the virus-induced oncogenesis of the breast.

Corrigendum: Human papillomavirus is associated with adenocarcinoma of lung: A population-based cohort study.

[This corrects the article DOI: 10.3389/fmed.2022.932196.].

Human Papillomavirus Is Associated With Adenocarcinoma of Lung: A Population-Based Cohort Study.

Background: Recent trends in the incidence of lung cancer have been reported despite the decreasing rate of smoking. Lung cancer is ranked among the top causes of cancer-related deaths. The ratio of adenocarcinoma to squamous cell carcinoma, as well as the ratio of women to men, is still increasing. Human papillomavirus (HPV) has been discovered in lung cancer tissues and blood specimens, particularly in Eastern countries. However, the association between HPV infection and lung adenocarcinoma remains unclear. Methods: This population-based cohort study was conducted using data from Taiwan's single-payer national health insurance and cancer registry databases. Data on HPV infection, cancer, sex, age, comorbidities, urbanization, and occupation were collected. The cumulative incidence rates were generated using Kaplan-Meier curves and log-rank tests. COX regression analysis was used to estimate the hazard ratios of factors associated with cancer occurrence. We used data from 2007 and 2015. The cases were matched with sex and age in a 1:2 manner with 939,874 HPV+ and 1,879,748 HPV- individuals, respectively. Results: The adjusted hazard ratios [95% confidence interval (CI)] for HPV infection in all lung cancers were 1.539 (1.436-1.649), male lung cancer 1.434 (1.312-1.566), female lung cancer 1.742 (1.557-1.948), squamous cell carcinoma (SCC) 1.092 (0.903-1.320), male SCC 1.092 (0.903-1.320), female SCC 0.949 (0.773-1.164), adenocarcinoma 1.714 (1.572-1.870), male adenocarcinoma 1.646 (1.458-1.858), and female adenocarcinoma 1.646 (1.458-1.858). The highest adjusted hazard ratio for lung cancer was chronic obstructive pulmonary disease (COPD) 1.799 (1.613-2.007), followed by male sex 1.567 (1.451-6.863) and HPV infection. The highest adjusted hazard ratio for adenocarcinoma was HPV infection 1.714 (1.572-1.870), followed by COPD 1.300 (1.102-1.533), and for SCC, male sex 5.645 (4.43-3.37), followed by COPD 2.528 (2.002-3.192). Conclusion: Our study showed that HPV infection was associated with the occurrence of adenocarcinoma of the lung in both men and women but was not associated with SCC of the lung.

The association between human papillomavirus infection and head and neck cancer: A population-based cohort study.

Human papillomavirus (HPV) has been linked with development of oropharyngeal squamous cell carcinoma, a subset of head and neck cancer (HNC). This study aimed to evaluate the association between HPV infection and subsequent development of HNC and to report epidemiological information in Taiwan.This population-based cohort study retrieved patient data from the longitudinal health insurance database (LHID) of Taiwan's National Health Insurance Research Database (NHIRD) from 2005 to 2010 and analyzed it retrospectively. The crude incidence rate and incidence rate ratios with 95% confidence intervals of HNC were estimated in patients with and without HPV infection. A time-to-event analysis was conducted and multiple regression analysis was performed to identify factors associated with HNC in HPV-infected patients, including age at baseline, sex, and comorbidities.This study included the data of 25,520 HPV-infected and 1,061,817 noninfected patients. The HPV-infected group had a significantly higher proportion of females than the noninfected group (55.80% vs 50.66%, respectively; P < .0001). The incidence rate of HNC was 11.49 (males) and 5.83 (females) per 10 person-months versus 11.38 (males) and 3.90 (females) per 10 person-months in the infected and noninfected groups, respectively. HPV was significantly associated with cancer in females (hazard ratio = 1.520, 95% confidence interval 1.166-1.981), but not in males (hazard ratio = 1.000, 95% confidence interval 0.815-1.228). No significant differences were found in age between the HPV-infected and noninfected patients (49.20 ±â€Š14.34 years vs 49.09 ±â€Š13.82 years, respectively); and a slightly higher percentage of HPV-infected patients had a specific comorbidity than did noninfected patients 12.54% versus 9.43%, ischemic heart disease 14.22% versus 10.51%, hypertension 22.40% versus 19.54%, liver disease 22.88% versus 16.17%, and renal disease 7.14% versus 5.39%, respectively.Results of this study may help clinicians in the diagnosis, prognosis, and treatment of head and neck cancer.