scholarly journals Case Report: Intra-Tumoral Vaccinations of Quadrivalent HPV-L1 Peptide Vaccine With Topical TLR-7 Agonist Following Recurrence: Complete Resolution of HPV-HR-Associated Gynecologic Squamous Cell Carcinomas in Two Patients

2021 ◽  
Vol 27 ◽  
Author(s):  
Mark Reedy ◽  
Shirisha Jonnalagadda ◽  
Komaraiah Palle

The human papilloma virus (HPV) high-risk variants (HPV-HR) such as HPV16 and HPV18 are responsible for most HPV related cancers, including anogenital and head and neck cancers. Here, we present two patients with HPV-HR-associated gynecological malignancies who, after failing radiation therapy, were treated with experimental salvage immunotherapy regimen resulting in complete, durable responses in both patients. Each patient was diagnosed with recurrent, radiation-refractory, HPV-HR positive, squamous cell carcinoma of the lower genital tract. Patient A was a 90-year-old, African American, with metastatic vulvar cancer to the right inguinal-femoral triangle and pulmonary metastases. Patient B was a 41-year-old, Caucasian, with a central-recurrence of cervix cancer. Each patient received at least two intratumoral quadrivalent HPV-L1 vaccine (Gardasil™) injections and daily topical TLR-7 agonist (imiquimod) to the tumor surface 2 weeks apart. This combination of intratumoral vaccinations and topical TLR-7 agonist produced unexpected complete resolution of disease in both patients. The importance of radiation therapy, despite being considered a treatment failure by current definitions, cannot be understated. Radiation therapy appears to have offered a therapeutic immune advantage by modifying the tumor microenvironment. This immune protocol has potential to help patients with advanced HPV-HR-related malignancies previously considered incurable.

2021 ◽  
Vol 162 ◽  
pp. S245-S246
Author(s):  
Kelly Bruce ◽  
Amy Alabaster ◽  
Arthur-Quan Tran

2017 ◽  
Vol 35 (7) ◽  
pp. 718-726 ◽  
Author(s):  
Madhur K. Garg ◽  
Fengmin Zhao ◽  
Joseph A. Sparano ◽  
Joel Palefsky ◽  
Richard Whittington ◽  
...  

Purpose Squamous cell carcinoma of the anal canal (SCCAC) is characterized by high locoregional failure (LRF) rates after sphincter-preserving definitive chemoradiation (CRT) and is typically associated with anogenital human papilloma virus infection. Because cetuximab enhances the effect of radiation therapy in human papilloma virus–associated oropharyngeal squamous cell carcinoma, we hypothesized that adding cetuximab to CRT would reduce LRF in SCCAC. Methods Sixty-one patients with stage I to III SCCAC received CRT including cisplatin, fluorouracil, and radiation therapy to the primary tumor and regional lymph nodes (45 to 54 Gy) plus eight once-weekly doses of concurrent cetuximab. The study was designed to detect at least a 50% reduction in 3-year LRF rate (one-sided α, 0.10; power 90%), assuming a 35% LRF rate from historical data. Results Poor risk features included stage III disease in 64% and male sex in 20%. The 3-year LRF rate was 23% (95% CI, 13% to 36%; one-sided P = .03) by binomial proportional estimate using the prespecified end point and 21% (95% CI, 7% to 26%) by Kaplan-Meier estimate in a post hoc analysis using methods consistent with historical data. Three-year rates were 68% (95% CI, 55% to 79%) for progression-free survival and 83% (95% CI, 71% to 91%) for overall survival. Grade 4 toxicity occurred in 32%, and 5% had treatment-associated deaths. Conclusion Although the addition of cetuximab to chemoradiation for SCCAC was associated with lower LRF rates than historical data with CRT alone, toxicity was substantial, and LRF still occurs in approximately 20%, indicating the continued need for more effective and less toxic therapies.


2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Diana V. Golub ◽  
A. Cahid Civelek ◽  
Vivek R. Sharma

The typically recommended chemotherapy options in metastatic anal cancer generally yield partial remissions with limited benefit for the majority of patients. TIP is a regimen containing paclitaxel (Taxol), ifosfamide, and cisplatin that is known to have significant activity in patients with squamous cell cancers of the head and neck as well as in cervical cancer, both of which are malignancies strongly associated with oncogenic strains of human papilloma virus (HPV). Interestingly, squamous cell cancer of the anal canal shares an almost identical pathophysiology including causal association with HPV. Due to this, we chose to use the TIP regimen to treat patients with advanced anal cancer at our institution and report our findings on three such consecutive patients. All the patients tolerated the regimen well with manageable side effects and had excellent responses with complete resolution of PET activity after treatment. Our observations suggest that TIP is highly active for squamous cell cancer of the anal canal and warrants further study in the treatment of this disease.


2019 ◽  
Vol 30 (1) ◽  
pp. 100-106 ◽  
Author(s):  
Lily Proctor ◽  
Lien Hoang ◽  
Jocelyn Moore ◽  
Emily Thompson ◽  
Samuel Leung ◽  
...  

IntroductionVulvar squamous cell carcinoma develops through two separate pathways, associated with the presence or absence of high-risk human papilloma virus (HPV). The objective of this study was to evaluate treatment response and clinical outcomes in women with HPV-associated versus HPV-independent vulvar squamous cell carcinoma treated with primary radiation therapy, in order to determine the ability to use HPV status as a predictor of response to radiation therapy.MethodsThis was a retrospective cohort study combining data from British Columbia Cancer, Canada and Duke University, USA. Patients were included who had been treated with radiation therapy but excluded if they had received major surgical interventions. Immunohistochemistry for p16 (as a surrogate for high-risk HPV infection) and p53 was performed. We analyzed the univariable association between p16 status and clinico-pathological features and performed univariable survival analysis for p16.ResultsForty-eight patients with vulvar squamous cell carcinoma treated with primary radiation therapy were identified: 26 p16 positive/HPV-associated patients and 22 p16 negative/HPV-independent patients. p16 positive vulvar squamous cell carcinoma demonstrated a significantly improved overall survival (HR 0.39, p=0.03) and progression-free survival (HR 0.35, p=0.02). In women treated with definitive radiation therapy, p16 positivity was associated with improved overall survival (HR 0.29, p<0.01) and progression-free survival (HR 0.21, p<0.01). Among patients who received sensitizing chemotherapy, a significant association was observed with p16 positive tumors and overall survival (HR 0.25, p=0.03) and progression-free survival (HR 0.09, p<0.01).ConclusionThis study suggests that HPV status in vulvar squamous cell carcinoma has both prognostic and predictive implications, with increased radiosensitivity demonstrated in HPV-associated vulvar squamous cell carcinoma. Implications may include radiation dose de-escalation for HPV-associated vulvar squamous cell carcinoma and increased surgical aggressiveness for HPV-independent vulvar squamous cell carcinoma.


2019 ◽  
Vol 8 (2) ◽  
Author(s):  
Takashi Matsushita ◽  
Tomoyasu Kumano ◽  
Kazuhiko Takehara

Primary cutaneous follicle center lymphoma (PCFCL) accounts for the majority of primary cutaneous B-cell lymphomas. We report a 60-year-old womanwith PCFCL. She had a red nodule (25 × 25 mm) on the right side of the lower jaw. She was diagnosed with PCFCL by skin biopsy. And then, she was treated with radiation therapy (total 30.6 Gy), which completely eliminated the nodule. Our case suggests that radiation therapy may be a first choice for PCFCL patients with a solitary lesion or localized lesions.    


We report a very rare case of squamous cell cancer of the right foot which had metastasize to the ipsilateral popliteal lymph node after initial diagnosis and treatment for the loco-regional disease.


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