Immunotherapeutic Approaches for the Treatment of HPV-Associated (Pre-)Cancer of the Cervix, Vulva and Penis

Rafael, Tynisha S.; Rotman, Jossie; Brouwer, O.R.; Poel, Henk G. van der; Mom, Constantijne H.; Kenter, Gemma G.; Gruijl, Tanja D. de; Jordanova, Ekaterina S.

doi:10.3390/jcm11041101

Cited by 12 publications

(8 citation statements)

References 219 publications

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“…The development of therapeutic vaccines represents an interesting challenge for the treatment of HPV infection of the lower genital tract. Indeed, the development of therapeutic vaccines may constitute a valid clinical treatment option; nevertheless, there are no vaccines of this nature currently available in clinical practice [ 13 , 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…Human Papillomavirus is a non-enveloped icosahedral virus with 72 capsomeres and a diameter of 55 nm. The genome is a circular double strand of DNA with a length of 8000 bp [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…Nine open reading frames make up the HPV genome, encoding for seven early genes (E1–E7 with regulatory properties in infected cells) and two late genes (L1–L2 encoding capsid proteins). Finally, the viral genome presents long control regions with a cis-acting regulatory sequence involved in the replication and the post-transcriptional controls [ 13 , 14 ]. These three different regions are expressed in different layers of the cervical tissue.…”

Section: Introductionmentioning

confidence: 99%

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New Perspectives in Therapeutic Vaccines for HPV: A Critical Review

et al. 2022

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Human Papillomavirus is the main cause of cervical cancer, including squamous cell carcinoma of the oropharynx, anus, rectum, penis, vagina, and vulva. In recent years, considerable effort has been made to control HPV-induced diseases using either prophylactic or therapeutic approaches. A critical review of the literature about the therapeutic Human Papillomavirus vaccine was performed to analyze its efficacy in the treatment of female lower genital tract lesions and its possible perspective application in clinical practice. The most important medical databases were consulted, and all papers published from 2000 until 2021 were considered. We retrieved a group of seven papers, reporting the role of anti HPV therapeutic vaccines against the L2 protein in the order of their efficacy and safety in female lower genital tract disease. In addition, the immune response due to vaccine administration was evaluated. The development of therapeutic vaccines represents an interesting challenge for the treatment of HPV infection of the lower genital tract. Literature data underline that the L2 protein may be an interesting and promising target in the development of therapeutic HPV vaccines, but the possible strengths and the unclear longevity of L2 immune responses are factors to be considered before clinical use.

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Section: Discussionmentioning

confidence: 99%

“…Human Papillomavirus is a non-enveloped icosahedral virus with 72 capsomeres and a diameter of 55 nm. The genome is a circular double strand of DNA with a length of 8000 bp [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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New Perspectives in Therapeutic Vaccines for HPV: A Critical Review

et al. 2022

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“…8,9 These findings provide a rationale to explore immunotherapeutic treatment for penile cancer. 10,11 Radiotherapy (RT) is used for control of symptomatic disease in penile cancer and may induce several immunogenic effects on the tumor microenvironment, such as increased tumor antigen release and upregulation of tumor PD-L1. 12 These effects can potentially enhance the therapeutic efficacy of PD-(L)1 blockade and synergistically promote antitumor immunity.…”

Section: Introductionmentioning

confidence: 99%

Atezolizumab With or Without Radiotherapy for Advanced Squamous Cell Carcinoma of the Penis (The PERICLES Study): A Phase II Trial

Vries

Rafael

Gil-Jimenez

et al. 2023

JCO

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PURPOSE Patients with advanced penile squamous cell carcinoma have a poor prognosis (21% 2-year overall survival [OS] from diagnosis). We assessed the activity of atezolizumab (anti–PD-L1) in patients with advanced penile cancer, with or without radiotherapy (RT). PATIENTS AND METHODS A single-center, nonrandomized phase II study with two treatment arms was conducted in 32 patients with histologically confirmed advanced penile cancer. All patients received atezolizumab (1,200 mg) once every 3 weeks. Twenty patients, who were expected to benefit from RT for locoregional disease control, received additional irradiation. The primary end point was 1-year progression-free survival (PFS) for the complete cohort and was reached if the actual 1-year PFS was at least 35%. Secondary end points included OS, objective response rate (ORR), and tolerability. Exploratory biomarker analyses were conducted in pretreatment specimens. RESULTS Median follow-up was 29.1 months (IQR, 18.1-33.5). Grade 3-4 adverse events related to atezolizumab or RT were observed in 3/32 (9.4%) and 13/20 (65%) patients, respectively. One-year PFS was 12.5% (95% CI, 5.0 to 31.3), which did not meet the study's primary end point. Median OS was 11.3 months (95% CI, 5.5 to 18.7). In the objective response-evaluable population (n = 30; 93.8%), the ORR was 16.7% (95% CI, 6 to 35), including 2 (6.7%) complete responders and 3 (10%) partial responders. Improved PFS was observed in patients with high-risk human papillomavirus (hrHPV)–positive tumors ( P = .003) and those with high infiltration of intratumoral CD3+CD8+ T cells ( P = .037). CONCLUSION Although the primary end point of 1-year PFS was not met, durable antitumor activity to atezolizumab was observed in a subset of patients. Biomarkers, such as hrHPV and intratumoral CD3+CD8+ T-cell infiltration, may help to better select responders.

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“…Just as higher expression of PDL1 correlates with improved response to ICI in other tumors ( 35 ), the high PDL1 expression rate in PSCC tissue suggests that ICI may be a potentially effective treatment for PSCC ( 36 ). In addition, the distinct molecular mechanisms and prognosis between HPV-positive and HPV-negative PSCC make HPV-related therapies, such as therapeutic HPV vaccines, a potential focus for penile cancer treatment ( 37 , 38 ). Moreover, adoptive T cells therapy (ATC) has also shown efficacy in treating advanced penile cancer in some early clinical trials, also emerging as a potential treatment for penile cancer ( 36 ).…”

Section: Introductionmentioning

confidence: 99%

Immune landscape and immunotherapy for penile cancer

Tang

et al. 2022

Front. Immunol.

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Penile cancer is a rare malignancy and usually refers to penile squamous cell carcinoma (PSCC), which accounts for more than 95% of all penile malignancies. Although organ-sparing surgery is an effective treatment for early-stage PSCC, surgical intervention alone is often not curative for advanced PSCC with metastases to the inguinal and/or pelvic lymph nodes; thus, systemic therapy is required (usually platinum-based chemotherapy and surgery combined). However, chemotherapy for PSCC has proven to be of limited efficacy and is often accompanied by high toxicity, and patients with advanced PSCC usually have poor prognosis. The limited treatment options and poor prognosis indicate the unmet need for advanced PSCC. Immune-based therapies have been approved for a variety of genitourinary and squamous cell carcinomas but are rarely reported in PSCC. To date, several studies have reported high expression of PDL1 in PSCC, supporting the potential application of immune checkpoint inhibitors in PSCC. In addition, human papillomavirus (HPV) infection is highly prevalent in PSCC and plays a key role in the carcinogenesis of HPV-positive PSCC, suggesting that therapeutic HPV vaccine may also be a potential treatment modality. Moreover, adoptive T cell therapy (ATC) has also shown efficacy in treating advanced penile cancer in some early clinical trials. The development of new therapeutics relies on understanding the underlying biological mechanisms and processes of tumor initiation, progression and metastasis. Therefore, based on the interest, we reviewed the tumor immune microenvironment and the emerging immunotherapy for penile cancer.

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Immunotherapeutic Approaches for the Treatment of HPV-Associated (Pre-)Cancer of the Cervix, Vulva and Penis

Cited by 12 publications

References 219 publications

New Perspectives in Therapeutic Vaccines for HPV: A Critical Review

New Perspectives in Therapeutic Vaccines for HPV: A Critical Review

Atezolizumab With or Without Radiotherapy for Advanced Squamous Cell Carcinoma of the Penis (The PERICLES Study): A Phase II Trial

Immune landscape and immunotherapy for penile cancer

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