Human papillomavirus in anal squamous cell carcinoma: an angel rather than a devil?

Ravenda, Paola Simona; Zampino, Maria Giulia; Fazio, Nicola; Barberis, Massimo; Bottiglieri, Luca; Chiocca, Susanna

doi:10.3332/ecancer.2015.529

Cited by 9 publications

(4 citation statements)

References 15 publications

(16 reference statements)

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“…In the present study, a large subset of patients with SCC of the anus (86%) or SCCHN (47%) had HPV-driven tumors similar to those observed in other studies. 13,16,37 However, the analysis is limited since HPV status was determined using a nonstandard approach (inferred from DNA sequencing using HPV-specific capture probes). This approach was used due to the limited amount of available tissue from the pretreatment biopsy, which precluded conducting both genomic profiling and assessing HPV by standard techniques such as in situ hybridization or p16 immunohistochemistry (IHC).…”

Section: Discussionmentioning

confidence: 99%

“…Patients with HPV-positive tumors have improved responses to chemotherapy and better outcomes compared to HPV-negative patients. 37–40 Since approximately 90% of patients with SCC of the anus are HPV-positive and since the incidence of SCC of the anus is low, 16,41 it will be difficult to design studies that assess HPV-negative patients with SCC of the anus. This is in contrast to recurrent/metastatic SCCHN, for which the number of patients who are HPV-positive are comparable to the number of patients who are HPV-negative.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study of Patients with Squamous Cell Carcinoma

Hong

Moore

Patel

et al. 2018

Clinical Cancer Research

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Prexasertib, a checkpoint kinase 1 inhibitor, demonstrated single-agent activity in patients with advanced squamous cell carcinoma (SCC) in the dose-escalation portion of a phase I study (NCT01115790). Monotherapy prexasertib was further evaluated in patients with advanced SCC. Patients were given prexasertib 105 mg/m as a 1-hour infusion on day 1 of a 14-day cycle. Expansion cohorts were defined by tumor and treatment line. Safety, tolerability, efficacy, and exploratory biomarkers were analyzed. Prexasertib was given to 101 patients, including 26 with SCC of the anus, 57 with SCC of the head and neck (SCCHN), and 16 with squamous cell non-small cell lung cancer (sqNSCLC). Patients were heavily pretreated (49% ≥3 prior regimens). The most common treatment-related adverse event was grade 4 neutropenia (71%); 12% of patients had febrile neutropenia. Median progression-free survival was 2.8 months [90% confidence interval (CI), 1.9-4.2] for SCC of the anus, 1.6 months (90% CI, 1.4-2.8) for SCCHN, and 3.0 months (90% CI, 1.4-3.9) for sqNSCLC. The clinical benefit rate at 3 months (complete response + partial response + stable disease) across tumors was 29% (23% SCC of the anus, 28% SCCHN, 44% sqNSCLC). Four patients with SCC of the anus had partial or complete response [overall response rate (ORR) = 15%], and three patients with SCCHN had partial response (ORR = 5%). Biomarker analyses focused on genes that altered DNA damage response or increased replication stress. Prexasertib demonstrated an acceptable safety profile and single-agent activity in patients with advanced SCC. The prexasertib maximum-tolerated dose of 105 mg/m was confirmed as the recommended phase II dose. .

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study of Patients with Squamous Cell Carcinoma

Hong

Moore

Patel

et al. 2018

Clinical Cancer Research

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“…High risk papilloma virus is associated with anal adenocarcinoma and anal squamous skin cancer [ 5 ], and HPV subtypes 16 and 18 have also been previously reported in ANEC [ 5 , 18 ]. Presence of HR-HPV may also be associated to a better outcome, as in stage III anal squamous cell carcinoma in which a more favorable response to chemotherapy has been seen with a better 5-year disease free survival (DFS) [ 19 ]. If this is true also for ANECs is not known.…”

Section: Discussionmentioning

confidence: 99%

Highly proliferative anal neuroendocrine carcinoma: molecular and clinical features of a rare, recurrent case in complete remission

et al. 2020

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Background: Poorly differentiated anal neuroendocrine carcinomas (ANECs) are rare lesions with poor prognosis, and the molecular etiology is only partially understood. Case presentation: At our institution, we have treated and followed a patient with such a rare ANEC. He had primarily surgery followed by three rounds of repeated surgery for loco-regional recurrences. He also received three different combinations of chemotherapy and external beam radiation. At last follow-up 13 years since the primary diagnosis, the patient had been in complete remission for nine years. The patient's medical files were reexamined , including laboratory, radiology and clinical examinations. Histopathology was reassessed , and expanded immunohistochemistry was performed from tissue specimens from the four surgical procedures. In addition, the molecular genetic status was evaluated through next-generation sequencing. The initial tumor was consistent with a 59 mm small cell neuroendocrine cancer with a Ki-67 index of 80%. Regional lymph node metastases were evident, and immunohistochemistry supported a neuroendocrine origin. A PCR screening detected human papilloma virus type 45 DNA (high-risk subtype), and focused next-generation sequencing found a missense mutation in the Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) gene. In tissues representing subsequent recurrences, the Chromogranin A expression was lost, and the Ki-67 index increased to 90%. Conclusions: For the first time, we report the detection of HPV45 in a case of ANEC. To our belief, PIK3CA mutations have also not been previously demonstrated in this tumor entity. In highly malignant ANECs, cure can in rare cases be achieved. Although speculative, expression of HPV45 and/or the PIK3CA mutation may have contributed to the favorable outcome.

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“…However, positive human papillomavirus status in combination with the overexpression of cyclin-dependent kinase inhibitor 2A (p16INK4a) yields improved treatment outcome http://theijpt.org [2][3][4]. On the other hand, human papillomavirus-negative tumors are associated with reduced local recurrence control rates and overall survival [5].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Dosimetric Robustness of Carbon Ion Boost Therapy for Anal Carcinoma

Kraus

Pfaffenberger

Jäkel

et al. 2016

International Journal of Particle Therapy

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Purpose: The radiation therapy treatment outcome of human papillomavirus–negative anal carcinoma may be improved by the biological effectiveness of carbon ions. However, abdominal tissue motion can compromise the precision of carbon ion therapy. This work aims to evaluate the dosimetric feasibility of carbon ion boost (CIB) therapy for anal carcinoma. Materials and Methods: An algorithm to generate computed tomographies based on daily magnetic resonance imaging data and deformable image registration was developed. By means of this algorithm, fractional computed tomography data for 54 treatment fractions for 3 different patients with anal carcinoma were derived. The dose for a sequential CIB (CIBseq) treatment plan was recalculated on the fractional computed tomography data and accumulated over the number of fractions. The resulting dose distributions were compared to standard intensity-modulated radiation therapy treatment with an integrated photon boost. Results: For the investigated patient cases, similar dosimetric results for CIBseq treatment and for intensity-modulated radiation therapy with an integrated photon boost were found. For CIBseq treatment, bladder-filling variation had the strongest influence on the dose distribution. However, the detrimental effects on the mean target dose remained below 1 Gy (RBE) as compared to photon therapy. Conclusion: This study shows the dosimetric feasibility of CIB therapy for anal carcinoma for the first time and gives reason for clinical exploitation of the enhanced biological effect of carbon ions for patients with human papillomavirus–negative anal cancer.

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Human papillomavirus in anal squamous cell carcinoma: an angel rather than a devil?

Cited by 9 publications

References 15 publications

Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study of Patients with Squamous Cell Carcinoma

Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study of Patients with Squamous Cell Carcinoma

Highly proliferative anal neuroendocrine carcinoma: molecular and clinical features of a rare, recurrent case in complete remission

Evaluation of Dosimetric Robustness of Carbon Ion Boost Therapy for Anal Carcinoma

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