Comparative molecular profiling of HPV‐induced squamous cell carcinomas

Abstract

Approximately 5% of all cancer incidences result from human papillomavirus (HPV) infection. HPV infection most commonly leads to cancers of the anogenital region or oropharynx. It is unknown whether different HPV‐mediated cancers collectively share a molecular signature and it is important to determine if there are targetable alterations common to different types of HPV‐positive tumors. We analyzed 743 p53 wild‐type samples of anal, cervical, oropharyngeal, and vulvar squamous cell carcinomas which underwent multiplatform testing at a commercial molecular profiling service. Expression of 24 proteins was measured by immunohistochemistry (IHC), mutation of 48 genes was determined by next‐generation and Sanger sequencing, and copy number alteration for six genes was determined by in situ hybridization. The four cohorts had remarkably similar molecular profiles. No gene had a statistically significant difference in mutation frequency or copy number change between the four different types of squamous cell carcinomas. The only significant differences between cohorts were frequency of ERCC1 and SPARC loss as determined by IHC. In all four cancer types, oncogene mutation and PD‐L1 expression was relatively infrequent. The most commonly mutated gene was PIK3CA, with mutations most often affecting the helical domain of the protein and accompanied by concurrent lack of PTEN expression. Loss of MGMT and RRM1 was common among the four cohorts and may be predictive of response to cytotoxic therapies not currently being used to treat these cancer types. The similar molecular profiles of the four cohorts indicate that treatment strategies may be similarly efficacious across HPV‐positive cancers.

A comparative study of p53 expression in premalignant and malignant cervical lesions at a tertiary care institute of Rohilkhand region, India

“…SCCs are the most common histological type as the most common etiological agent responsible for cervical cancer is HPV which most commonly affects the lining cervical [19,23] epithelium. HSIL was the common histological subtype in premalignant lesions in the present study which is in concordance to the studies done by Jeffers et al [24] The mean age of presentation of malignant lesions (49.04 ± 10.42 years) is almost similar to that reported by Rajaram et al [25] (52.1 ± 12.46 years), Tan et al [26] (51.1 years), Koncar et al [27] (50 years), and Tan et al [28] (50.3 years). Furthermore, the mean age of presentation of premalignant lesions (41.00 ± 8.89 years) is younger than that of malignant lesions.…”

Absence of disruptive TP53 mutations in high‐risk human papillomavirus‐driven neck squamous cell carcinoma of unknown primary

“…These data are remarkably consistent with those from patients with OPSCC showing an inverse relationship between hrHPV infection and disruptive TP53 mutations in the primary tumor . Furthermore, overexpression of p16 INK4a , as surrogate marker for HPV‐driven carcinomas, was recently found to be associated with TP53 wild‐type status in both primary and metastatic site of OPSCC and other HPV‐associated cancers, that is, cervical, anal, and vulvar SCC . In a series of HNSCC inclusive of 20 NSCCUP, Bersani et al found that the frequency of hotspot mutations in several oncogenes and tumor suppressor genes, including TP53 , was similarly less frequent in HPV‐positive OPSCC and HPV‐positive NSCCUP compared to HPV‐negative OPSCC …”

“…24,[26][27][28] Furthermore, overexpression of p16 INK4a , as surrogate marker for HPV-driven carcinomas, was recently found to be associated with TP53 wild-type status in both primary and metastatic site of OPSCC and other HPV-associated cancers, that is, cervical, anal, and vulvar SCC. 29 In a series of HNSCC inclusive of 20 NSCCUP, Bersani et al found that the frequency of hotspot mutations in several oncogenes and tumor suppressor genes, including TP53, was similarly less frequent in HPV-positive OPSCC and HPV-positive NSCCUP compared to HPV-negative OPSCC. 30 In our TP53 mutation analysis, the amplification and sequencing success rate was limited by poor quality and low concentration of DNA isolated from FFPE tissue, which is often observed in retrospective studies using archived F I G U R E 1 Flow diagram of the HPV and TP53 status results from formalin-fixed, paraffin-embedded neck squamous cell carcinoma of unknown primary included in this study.…”

The Molecular Pathogenesis of Trichilemmal Carcinoma

“…Moreover, PTEN deletion, identi ed in Case 2, frequently accompanied HPV-induced squamous cell carcinoma. 18 These ndings imply that HPV may play a leading role in TC carcinogenesis.…”