Human Papillomavirus in Non-Small Cell Lung Carcinoma: Assessing Virus Presence in Tumor and Normal Tissues and Its Clinical Relevance

Abstract

The significance of the role of human papillomavirus (HPV) in the development of lung cancer remains an open question. The data from the literature do not provide conclusive evidence of HPV being involved in the pathogenesis of lung cancer. The aim of this work was to detect the presence of HPV infections with a high carcinogenic risk in patients with non-small cell lung cancer (NSCLC). Materials and methods: the study involved 274 patients with stage IIA–IIIB non-small cell lung cancer. We analyzed normal and tumor tissues as well as blood from each patient. DNA was extracted from patients’ specimens, and HPV detection and genotyping was carried out using commercially available kits by PCR. Results: HPV was detected in 12.7% of the patients (35/274 of all cases). We detected nine different types of human papillomavirus in the patients, namely, types 16, 18, 31, 35, 45, 51, 52, 56, and 59. The HPV-positive samples had a clinically insignificant viral load and were predominantly integrated. The relationship between the presence of HPV and its virological parameters and the clinical and pathological parameters of the patients was established. A metastatic-free survival analysis showed that all patients with HPV in the tumor tissue had a higher 5-year survival rate (94%) compared with the HPV-negative patients (78%). The result was not statistically significant (p = 0.08). Conclusions: data showing a 12.7% human papillomavirus representation among patients with non-small cell lung cancer were obtained. The presence/absence of a viral component in patients with lung cancer was a clinically significant parameter. HPV types 16, 18, and 56, which are the most oncogenic, were most often detected.

The Role of Human Papilloma Virus (HPV) in Primary Lung Cancer Development: State of the Art and Future Perspectives

“…Particularly for lung cancer, nine high-risk HPV genotypes were recently detected in patients with NSCLC, i.e., 16, 18, 31, 35, 45, 51, 52, 56, and 59 [26], and often multiple HPV types were concurrently observed in lung tissues [26]. The most frequently detected HPV genotypes were 16, 18, and 56 [27][28][29][30].…”

“…HPV-DNA was discovered not only in neoplastic lung cells [4][5][6]11,27] but also in human blood [6,11,27] and peripheral mononuclear cells [6]. The integrated form of HPV-DNA was identified in tissue samples of patients affected by NSCLC, while the episomal and mixed forms were identified in blood samples [26]. In 2023, Sun et al used the Mendelian randomization to provide extensive analysis on the causal effect of HPV in cancer development [31].…”

“…Mendelian randomization is an epidemiological method to analyze the casual relationship between HPV exposure and outcomes by using single nucleotide polymorphisms [31]. Using this method on a large HPV16/17 protein exposure dataset, the authors demonstrated how HPV18 E7 exposure posed to be a risk factor for NSCLC development [26]. In a very recent and valid meta-analysis, Drokow et al [11] showed that patients infected with HPV type 16 were at a higher risk for NSCLC development compared to those infected with type 18 (OR = 1.95, 95% CI: 1.00-3.79).…”

“…This observation suggests the possibility of bloodstream transmission, which could serve as a route of dissemination [8,33] alongside oral (through unprotected oral sex) and airborne transmission [6,32] (through exhaled air), Figure 3. The detection of high-risk HPV16 and 18 in lung cancer cells varies based on geographic areas [6] with the highest incidence observed in Asia (40.3%), followed by Latin America (33.6%), Europe (25.6%), North America (15.4%), Japan (16.9%) [34], and Russia (12.7%) [26]. In Italy, HPV prevalence in NSCLC ranges between 0 and 21.1% [6], Figure 4.…”

“…The detection of high-risk HPV16 and 18 in lung cancer cells varies based on geographic areas [6] with the highest incidence observed in Asia (40.3%), followed by Latin America (33.6%), Europe (25.6%), North America (15.4%), Japan (16.9%) [34], and Russia (12.7%) [26]. In Italy, HPV prevalence in NSCLC ranges between 0 and 21.1% [6], Figure 4.…”