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Journal of the National Cancer Institute Dec 2023The emergence of human papillomavirus (HPV)-positive oropharyngeal cancer and evolving tobacco use patterns have changed the landscape of head and neck cancer...
BACKGROUND
The emergence of human papillomavirus (HPV)-positive oropharyngeal cancer and evolving tobacco use patterns have changed the landscape of head and neck cancer epidemiology internationally. We investigated updated trends in oropharyngeal cancer incidence worldwide.
METHODS
We analyzed cancer incidence data between 1993 and 2012 from 42 countries using the Cancer Incidence in Five Continents database volumes V through XI. Trends in oropharyngeal cancer incidence were compared with oral cavity cancers and lung squamous cell carcinomas using log-linear regression and age period-cohort modeling.
RESULTS
In total, 156 567 oropharyngeal cancer, 146 693 oral cavity cancer, and 621 947 lung squamous cell carcinoma patients were included. Oropharyngeal cancer incidence increased (P < .05) in 19 and 23 countries in men and women, respectively. In countries with increasing male oropharyngeal cancer incidence, all but 1 had statistically significant decreases in lung squamous cell carcinoma incidence, and all but 2 had decreasing or nonsignificant net drifts for oral cavity cancer. Increased oropharyngeal cancer incidence was observed both in middle-aged (40-59 years) and older (≥60 years) male cohorts, with strong nonlinear birth cohort effects. In 20 countries where oropharyngeal cancer incidence increased for women and age period-cohort analysis was possible, 13 had negative or nonsignificant lung squamous cell carcinoma net drifts, including 4 countries with higher oropharyngeal cancer net drifts vs both lung squamous cell carcinoma and oral cavity cancer (P < .05 for all comparisons).
CONCLUSIONS
Increasing oropharyngeal cancer incidence is seen among an expanding array of countries worldwide. In men, increased oropharyngeal cancer is extending to older age groups, likely driven by human papillomavirus-related birth cohort effects. In women, more diverse patterns were observed, suggesting a complex interplay of risks factors varying by country, including several countries where female oropharyngeal cancer increases may be driven by HPV.
Topics: Middle Aged; Humans; Male; Female; Aged; Incidence; Papillomavirus Infections; Oropharyngeal Neoplasms; Head and Neck Neoplasms; Mouth Neoplasms; Carcinoma, Squamous Cell; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms
PubMed: 37603716
DOI: 10.1093/jnci/djad169 -
Journal of Clinical Oncology : Official... Mar 2024Standard curative-intent chemoradiotherapy for human papillomavirus (HPV)-related oropharyngeal carcinoma results in significant toxicity. Since hypoxic tumors are...
PURPOSE
Standard curative-intent chemoradiotherapy for human papillomavirus (HPV)-related oropharyngeal carcinoma results in significant toxicity. Since hypoxic tumors are radioresistant, we posited that the aerobic state of a tumor could identify patients eligible for de-escalation of chemoradiotherapy while maintaining treatment efficacy.
METHODS
We enrolled patients with HPV-related oropharyngeal carcinoma to receive de-escalated definitive chemoradiotherapy in a phase II study (ClinicalTrials.gov identifier: NCT03323463). Patients first underwent surgical removal of disease at their primary site, but not of gross disease in the neck. A baseline F-fluoromisonidazole positron emission tomography scan was used to measure tumor hypoxia and was repeated 1-2 weeks intratreatment. Patients with nonhypoxic tumors received 30 Gy (3 weeks) with chemotherapy, whereas those with hypoxic tumors received standard chemoradiotherapy to 70 Gy (7 weeks). The primary objective was achieving a 2-year locoregional control (LRC) of 95% with a 7% noninferiority margin.
RESULTS
One hundred fifty-eight patients with T0-2/N1-N2c were enrolled, of which 152 patients were eligible for analyses. Of these, 128 patients met criteria for 30 Gy and 24 patients received 70 Gy. The 2-year LRC was 94.7% (95% CI, 89.8 to 97.7), meeting our primary objective. With a median follow-up time of 38.3 (range, 22.1-58.4) months, the 2-year progression-free survival (PFS) and overall survival (OS) rates were 94% and 100%, respectively, for the 30-Gy cohort. The 70-Gy cohort had similar 2-year PFS and OS rates at 96% and 96%, respectively. Acute grade 3-4 adverse events were more common in 70 Gy versus 30 Gy (58.3% 32%; = .02). Late grade 3-4 adverse events only occurred in the 70-Gy cohort, in which 4.5% complained of late dysphagia.
CONCLUSION
Tumor hypoxia is a promising approach to direct dosing of curative-intent chemoradiotherapy for HPV-related carcinomas with preserved efficacy and substantially reduced toxicity that requires further investigation.
Topics: Humans; Human Papillomavirus Viruses; Papillomavirus Infections; Oropharyngeal Neoplasms; Chemoradiotherapy; Carcinoma; Hypoxia
PubMed: 38241600
DOI: 10.1200/JCO.23.01308 -
JAMA Oncology Aug 2023Xerostomia is a major toxic effect associated with intensity-modulated radiotherapy (IMRT) for oropharyngeal cancers.
Weekly Adaptive Radiotherapy vs Standard Intensity-Modulated Radiotherapy for Improving Salivary Function in Patients With Head and Neck Cancer: A Phase 3 Randomized Clinical Trial.
IMPORTANCE
Xerostomia is a major toxic effect associated with intensity-modulated radiotherapy (IMRT) for oropharyngeal cancers.
OBJECTIVE
To assess whether adaptive radiotherapy (ART) improves salivary function compared with IMRT in patients with head and neck cancer.
DESIGN, SETTING, AND PARTICIPANTS
This phase 3 randomized clinical trial was conducted in 11 French centers. Patients aged 18 to 75 years with stage III-IVB squamous cell oropharyngeal cancer treated with chemoradiotherapy were enrolled between July 5, 2013, and October 1, 2018. Data were analyzed from November 2021 to May 2022.
INTERVENTIONS
The patients were randomly assigned (1:1) to receive standard IMRT (without replanning) or ART (systematic weekly replanning).
MAIN OUTCOMES AND MEASURES
The primary end point was the frequency of xerostomia, measured by stimulating salivary flow with paraffin. Secondary end points included salivary gland excretory function measured using technetium-99m pertechnetate scintigraphy, patient-reported outcomes (Eisbruch xerostomia-specific questionnaire and the MD Anderson Symptom Inventory for Head and Neck Cancer questionnaire), early and late toxic effects, disease control, and overall and cancer-specific survival.
RESULTS
A total of 132 patients were randomized, and after 1 exclusion in the ART arm, 131 were analyzed: 66 in the ART arm (mean [SD] age at inclusion, 60 [8] years; 57 [86.4%] male) and 65 in the standard IMRT arm (mean [SD] age at inclusion, 60 [8] years; 57 [87.7%] male). The median follow-up was 26.4 months (IQR, 1.2-31.3 months). The mean (SD) salivary flow (paraffin) at 12 months was 630 (450) mg/min in the ART arm and 584 (464) mg/min in the standard arm (P = .64). The mean (SD) excretory function of the parotid gland at 12 months, measured by scintigraphy, improved in the ART arm (48% [17%]) compared with the standard arm (41% [17%]) (P = .02). The 2-year-overall survival was 76.9% (95% CI, 64.7%-85.4%) in both arms.
CONCLUSIONS AND RELEVANCE
This randomized clinical trial did not demonstrate a benefit of ART in decreasing xerostomia compared with standard IMRT. No significant differences were found in secondary end points except for parotid gland excretory function, as assessed by scintigraphy, or in survival rates.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01874587.
Topics: Humans; Male; Female; Radiotherapy, Intensity-Modulated; Paraffin; Head and Neck Neoplasms; Xerostomia; Parotid Gland; Oropharyngeal Neoplasms
PubMed: 37261806
DOI: 10.1001/jamaoncol.2023.1352 -
BMC Medical Genomics Aug 2023Observational studies have reported controversial results on the association between obesity and head and neck cancer risk. This study aimed to perform a two-sample...
BACKGROUND
Observational studies have reported controversial results on the association between obesity and head and neck cancer risk. This study aimed to perform a two-sample Mendelian randomization (MR) analysis to assess the causal association between obesity and head and neck cancer risk using publicly available genome-wide association studies (GWAS) summary statistics.
METHODS
Single-nucleotide polymorphisms (SNPs) for obesity [body mass index (BMI), waist-to-hip ratio (WHR), whole body fat mass, lean body mass, and trunk fat mass] and head and neck cancer (total head and neck cancer, oral cavity cancer, oropharyngeal cancer, and oral cavity and oropharyngeal cancer) were retrieved from published GWASs and used as genetic instrumental variables. Five methods including inverse-variance-weighted (IVW), weighted-median, MR-Egger, weighted mode, and MR-PRESSO were used to obtain reliable results, and odds ratio with 95% confidence interval (CI) were calculated. Tests for horizontal pleiotropy, heterogeneity, and sensitivity were performed separately.
RESULTS
Genetically predicted BMI was negatively associated with the risk of total head and neck cancer, which was significant in the IVW [OR (95%CI), 0.990 (0.984-0.996), P = 0.0005], weighted-median [OR (95%CI), 0.984 (0.975-0.993), P = 0.0009], and MR-PRESSO [OR (95%CI), 0.990 (0.984-0.995), P = 0.0004] analyses, but suggestive significant in the MR-Egger [OR (95%CI), 0.9980 (0.9968-0.9991), P < 0.001] and weighted mode [OR (95%CI), 0.9980 (0.9968-0.9991), P < 0.001] analyses. Similar, genetically predicted BMI adjust for smoking may also be negatively associated with the risk of total head and neck cancer (P < 0.05). Genetically predicted BMI may be negatively related to the risk of oral cavity cancer, oropharyngeal cancer, and oral cavity and oropharyngeal cancer (P < 0.05), but no causal association was observed for BMI adjust for smoking (P > 0.05). In addition, no causal associations were observed for other exposures and outcomes (all P > 0.05).
CONCLUSION
This MR analysis supported the causal association of BMI-related obesity with decreased risk of total head and neck cancer. However, the effect estimates from the MR analysis were close to 1, suggesting a slight protective effect of BMI-related obesity on head and neck cancer risk.
Topics: Humans; Genome-Wide Association Study; Mendelian Randomization Analysis; Head and Neck Neoplasms; Oropharyngeal Neoplasms; Mouth Neoplasms; Obesity
PubMed: 37620971
DOI: 10.1186/s12920-023-01634-4 -
European Archives of... Sep 2023The causative and prognostic roles of human papillomavirus (HPV) in non-oropharyngeal squamous cell carcinoma of the head and neck are uncertain. This umbrella review... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The causative and prognostic roles of human papillomavirus (HPV) in non-oropharyngeal squamous cell carcinoma of the head and neck are uncertain. This umbrella review assessed the strength and quality of evidence and graded the evidence derived from published meta-analyses on this subject.
DATA SOURCES
MEDLINE, Embase, and the Cochrane Library were searched. Meta-analyses of observational studies and randomized trials were included.
REVIEW METHODS
Evidence of association was graded according to the established criteria: strong, highly suggestive, suggestive, weak, or not significant.
RESULTS
15 meta-analyses were evaluated. The association with HPV was highly suggestive of oral (OR = 2.40, [1.87-3.07], P < 0.00001) and nasopharyngeal cancers (OR = 17.82 [11.20-28.35], P < 0.00001). Improved survival emerged only in hypopharyngeal carcinoma and was confirmed in studies in which only p16 + cancers were considered.
CONCLUSION
HPV infection may increase the risk of oral cavity and nasopharyngeal cancer. However, the prognosis was not influenced, except in hypopharyngeal carcinoma.
Topics: Humans; Papillomavirus Infections; Human Papillomavirus Viruses; Nasopharyngeal Neoplasms; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Mouth; Oropharyngeal Neoplasms; Papillomaviridae
PubMed: 37212863
DOI: 10.1007/s00405-023-08027-4 -
Journal of Medical Virology Nov 2023High-risk human papillomaviruses (HR-HPVs) cause various malignancies in the anogenital and oropharyngeal regions. About 70% of cervical and oropharyngeal cancers are... (Review)
Review
High-risk human papillomaviruses (HR-HPVs) cause various malignancies in the anogenital and oropharyngeal regions. About 70% of cervical and oropharyngeal cancers are caused by HPV types 16 and 18. Notably, some viruses including herpes simplex virus, Epstein-Barr virus, and human immunodeficiency virus along with various bacteria often interact with HPV, potentially impacting its replication, persistence, and cancer progression. Thus, HPV infection can be significantly influenced by co-infecting agents that influence infection dynamics and disease progression. Bacterial co-infections (e.g., Chlamydia trachomatis) along with bacterial vaginosis-related species also interact with HPV in genital tract leading to viral persistence and disease outcomes. Co-infections involving HPV and diverse infectious agents have significant implications for disease transmission and clinical progression. This review explores multiple facets of HPV infection encompassing the co-infection dynamics with other pathogens, interaction with the human microbiome, and its role in disease development.
Topics: Female; Humans; Papillomavirus Infections; Coinfection; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Neoplasms; Papillomaviridae
PubMed: 37997472
DOI: 10.1002/jmv.29236 -
Laryngo- Rhino- Otologie Jun 2024
Topics: Humans; Oropharyngeal Neoplasms; Robotic Surgical Procedures; Combined Modality Therapy
PubMed: 38830354
DOI: 10.1055/a-2216-7575 -
Laryngo- Rhino- Otologie May 2024
Topics: Humans; Papillomavirus Infections; Oropharyngeal Neoplasms; Carcinoma, Squamous Cell
PubMed: 38697086
DOI: 10.1055/a-2287-8402 -
Journal of Dental Hygiene : JDH Apr 2024
Topics: Humans; Oropharyngeal Neoplasms; Mouth Neoplasms; Papillomavirus Infections; Risk Factors
PubMed: 38649287
DOI: No ID Found -
Viruses Apr 2024The human papillomavirus is the most common sexually transmitted infection in the world. Most HPV infections clear spontaneously within 2 years of infection; however,... (Review)
Review
The human papillomavirus is the most common sexually transmitted infection in the world. Most HPV infections clear spontaneously within 2 years of infection; however, persistent infection can result in a wide array of diseases, ranging from genital warts to cancer. Most cases of cervical, anal, and oropharyngeal cancers are due to HPV infection, with cervical cancer being one of the leading causes of cancer death in women worldwide. Screening is available for HPV and cervical cancer, but is not available everywhere, particularly in lower-resource settings. HPV infection disproportionally affects individuals living with HIV, resulting in decreased clearance, increased development of cancer, and increased mortality. The development of the HPV vaccine has shown a drastic decrease in HPV-related diseases. The vaccine prevents cervical cancer with near 100% efficacy, if given prior to first sexual activity. Vaccination uptake remains low worldwide due to a lack of access and limited knowledge of HPV. Increasing awareness of HPV and access to vaccination are necessary to decrease cancer and HPV-related morbidity and mortality worldwide.
Topics: Humans; Papillomavirus Infections; Papillomavirus Vaccines; Female; Uterine Cervical Neoplasms; Papillomaviridae; Neoplasms; Vaccination; Anus Neoplasms; HIV Infections; Oropharyngeal Neoplasms; Male; Human Papillomavirus Viruses
PubMed: 38793561
DOI: 10.3390/v16050680