Human Papillomavirus-Related Carcinomas of the Sinonasal Tract

Lopez, Diana; Hoke, Austin T. K.; Rooper, Lisa M.; London, Nyall R.

doi:10.1007/s40136-022-00404-7

Cited by 5 publications

(14 citation statements)

References 117 publications

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“…In vivo, a single cycle of cisplatin or E7-specific CTL ACT failed to mediate significant tumor control as monotherapies, whereas in combination they demonstrated synergy, mediating significant tumor control (figure 5)-while employing the least remarkable HPV-associated tumor model from the in vitro phase of study (figure 3). These results build on a previous study characterizing the E7-specific TCR employed here, which demonstrated tumor control following ACT of 1×10 7 CTLs, whereas 1×10 6 CTLs had no effect. 21 Here, we observed that ACT of 1×10 6 E7-specific CTLs had no effect alone but was potentiated to mediate significant tumor control when combined with a single, subtherapeutic cycle of cisplatin (figure 5).…”

Section: Discussionsupporting

confidence: 88%

“…5 6 Sinonasal squamous cell carcinoma (SNSCC) is a rare subtype of HNSCC of the nasal cavities and paranasal sinuses. 7 When feasible, the typical first-line treatment is surgical resection. However, due to the close anatomic proximity to the skull base, orbits, and critical neurovascular structures, achieving negative surgical margins can be challenging.…”

Section: What This Study Addsmentioning

confidence: 99%

“…7 9 Interestingly, it has recently been demonstrated that HPV is present in about one in three cases of SNSCC, raising the question whether the problem of residual disease and disease recurrence can be addressed with HPV-targeting immuno-oncology (IO) strategies. 7 Whereas radiation and chemotherapy are primarily purposed as cytotoxic therapies in their clinical use, the last two decades have characterized an immunogenic potential for these standard therapies through the induction of immunogenic cell stress, resulting in phenotypic changes ranging from immunogenic modulation to immunogenic cell death. This body of investigation, though, has sparsely included representation of HPV-associated malignancies.…”

Section: What This Study Addsmentioning

confidence: 99%

“… 8 9 Nonetheless, outcomes in SNSCC remain dismal, with a 5-year survival rate of about 50% owing to advanced stage of disease at diagnosis and high rates of recurrence ranging from 40% to 80%. 7 9 Interestingly, it has recently been demonstrated that HPV is present in about one in three cases of SNSCC, raising the question whether the problem of residual disease and disease recurrence can be addressed with HPV-targeting immuno-oncology (IO) strategies. 7 …”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Exploiting the immunogenic potential of standard of care radiation or cisplatin therapy in preclinical models of HPV-associated malignancies

Kowalczyk

Fabian

Padget

et al. 2022

J Immunother Cancer

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BackgroundWhile radiation and chemotherapy are primarily purposed for their cytotoxic effects, a growing body of preclinical and clinical evidence demonstrates an immunogenic potential for these standard therapies. Accordingly, we sought to characterize the immunogenic potential of radiation and cisplatin in human tumor models of HPV-associated malignancies. These studies may inform rational combination immuno-oncology (IO) strategies to be employed in the clinic on the backbone of standard of care, and in so doing exploit the immunogenic potential of standard of care to improve durable responses in HPV-associated malignancies.MethodsRetroviral transduction with HPV16 E7 established a novel HPV-associated sinonasal squamous cell carcinoma (SNSCC) cell line. Three established HPV16-positive cell lines were also studied (cervical carcinoma and head and neck squamous cell carcinoma). Following determination of sensitivities to standard therapies using MTT assays, flow cytometry was used to characterize induction of immunogenic cell stress following sublethal exposure to radiation or cisplatin, and the functional consequence of this induction was determined using impedance-based real time cell analysis cytotoxicity assays employing HPV16 E7-specific cytotoxic lymphocytes (CTLs) with or without N803 (IL-15/IL-15-Rα superagonist) or exogenous death receptor ligands. In vitro observations were translated using an in vivo xenograft NSG mouse model of human cervical carcinoma evaluating cisplatin in combination with CTL adoptive cell transfer.ResultsWe showed that subpopulations surviving clinically relevant doses of radiation or cisplatin therapy were more susceptible to CTL-mediated lysis in four of four tumor models of HPV-associated malignancies, serving as a model for HPV therapeutic vaccine or T-cell receptor adoptive cell transfer. This increased killing was further amplified by IL-15 agonism employing N803. We further characterized that radiation or cisplatin induced immunogenic cell stress in three of three cell lines, and consequently demonstrated that upregulated surface expression of Fas and TRAIL-R2 death receptors at least in part mediated enhanced CTL-mediated lysis. In vivo, cisplatin-induced immunogenic cell stress synergistically potentiated CTL-mediated tumor control in a human model of HPV-associated malignancy.ConclusionStandard of care radiation or cisplatin therapy induced immunogenic cell stress in preclinical models of HPV-associated malignancies, presenting an opportunity poised for exploitation by employing IO strategies in combination with standard of care.

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Section: Discussionsupporting

confidence: 88%

Section: What This Study Addsmentioning

confidence: 99%

Section: What This Study Addsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Exploiting the immunogenic potential of standard of care radiation or cisplatin therapy in preclinical models of HPV-associated malignancies

Kowalczyk

Fabian

Padget

et al. 2022

J Immunother Cancer

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Epidemiologic Trends in Human Papillomavirus–Associated Sinonasal Squamous Cell Carcinoma

Amanian,

Ishii,

Fakhry

et al. 2024

JAMA Otolaryngol Head Neck Surg

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ImportanceSinonasal squamous cell carcinoma (SNSCC) is the most commonly encountered cancer within the sinonasal cavity. Ongoing research has sought to ascertain the potential role of human papillomavirus (HPV) in the pathogenesis of SNSCC.ObjectiveTo assess trends in HPV-associated and HPV-independent SNSCC over time, including assessment of clinical demographics, treatment patterns, and survival.Design, Setting, and ParticipantsThis cohort study used patient data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program database between 1975 and 2018. Anatomic sites with a greater predilection for HPV positivity (ie, nasal cavity, ethmoid sinus) were used as a surrogate for HPV-associated SNSCC; meanwhile, patients with SNSCC in the other subsites were classified into the HPV-independent group. Data were analyzed from August 2022 to May 2023.Main Outcomes and MeasuresClinical demographics and mortality trends over time were described for the HPV-associated and HPV-independent groups and further stratified according to stage on presentation.ResultsThe study population consisted of 3752 patients with SNSCC (mean [SD] age at diagnosis, 65.7 [13.3] years; 2417 [64.4%] male), with 1983 (52.9%) having HPV-associated SNSCC and 1769 (47.1%) with HPV-independent SNSCC. Patients with HPV-associated subsites compared with patients with HPV-independent SNSCC were more likely to present with localized disease (838 [42.3%] vs 162 [9.2%]), whereas more patients in the HPV-independent group than HPV-associated group presented with regional disease (1018 [57.5%] vs 480 [24.2%]). Incidence-based mortality was stable over time within the HPV-associated group (0.32%) and, conversely, showed a significant decrease within the HPV-independent group (−2.29%). Patients with HPV-associated SNSCC had a higher 5-year overall survival when compared with the HPV-independent group (62% vs 35% [difference, 27 percentage points; 95% CI, 23-31 percentage points]). The better 5-year overall survival in the HPV-associated group vs HPV-independent group was present across all disease stages (localized: hazard ratio [HR], 2.67; 95% CI, 1.96-3.65; regional: HR, 1.53; 95% CI, 1.29-1.82; and distant: HR, 1.97; 95% CI, 1.52-2.55).Conclusions and RelevanceThis cohort study showed that the proportion of HPV-associated SNSCC rose over time associated with both a rise in the proportion of nasal cavity SNSCC and a decrease in HPV-independent maxillary sinus SNSCC. These data suggest that HPV-associated SNSCC has a distinct demographic and prognostic profile, given the improved survival seen in patients with HPV-associated SNSCC.

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A diagnostic approach to small round cell epithelial and neuroepithelial tumours of the sinonasal tract

Adamane,

Weir

2024

Diagnostic Histopathology

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Human Papillomavirus-Related Carcinomas of the Sinonasal Tract

Cited by 5 publications

References 117 publications

Exploiting the immunogenic potential of standard of care radiation or cisplatin therapy in preclinical models of HPV-associated malignancies

Exploiting the immunogenic potential of standard of care radiation or cisplatin therapy in preclinical models of HPV-associated malignancies

Epidemiologic Trends in Human Papillomavirus–Associated Sinonasal Squamous Cell Carcinoma

A diagnostic approach to small round cell epithelial and neuroepithelial tumours of the sinonasal tract

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