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. 2022 Aug;7(4):100500.
doi: 10.1016/j.esmoop.2022.100500. Epub 2022 Jun 23.

Human papillomavirus infection and lung adenocarcinoma: special benefit is observed in patients treated with immune checkpoint inhibitors

L Rojas  1 , D Mayorga  2 , A Ruiz-Patiño  2 , J Rodríguez  2 , A F Cardona  3 , P Archila  2 , J Avila  2 , M Bravo  2 , L Ricaurte  4 , C Sotelo  2 , O Arrieta  5 , Z L Zatarain-Barrón  5 , H Carranza  1 , J Otero  1 , C Vargas  1 , F Barrón  5 , L Corrales  6 , C Martín  7 , G Recondo  8 , L E Pino  9 , M A Bermudez  2 , T Gamez  2 , C Ordoñez-Reyes  2 , J E García-Robledo  10 , V C de Lima  11 , H Freitas  12 , N Santoyo  2 , U Malapelle  13 , A Russo  14 , C Rolfo  15 , R Rosell  16 ; CLICaP
Affiliations

Human papillomavirus infection and lung adenocarcinoma: special benefit is observed in patients treated with immune checkpoint inhibitors

L Rojas et al. ESMO Open. 2022 Aug.

Abstract

Background: Human papilloma virus (HPV) has been associated with the development and modulation of response in a series of neoplasms. In the case of lung adenocarcinoma, its role in etiology and pathogenesis is still controversial. Considering that this infection brings foreign epitopes, it could be of prognostic significance in patients with lung adenocarcinoma treated with immunotherapy.

Methods: In a retrospective cohort study we evaluated the presence of HPV genomic material in lung adenocarcinoma primary lesions with the INNO-LiPA platform. Viral replication was also evaluated by detecting the presence of oncoprotein E6/E7 messenger RNA (mRNA) by quantitative RT-PCR. To confirm possible hypotheses regarding viral oncogenesis, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF1) were evaluated with stromal fibrosis and immunoscore.

Results: A total of 133 patients were included in the analysis, of whom 34 tested positive for HPV, reaching an estimated prevalence of 25.6% [95% confidence interval (CI) 18.2% to 32.9%]. E6/7 mRNA was identified in 28 out of the 34 previously positive cases (82.3%). In immune checkpoint inhibitor (ICI)-treated patients, the median overall survival reached 22.3 months [95% CI 19.4 months- not reached (NR)] for HPV-negative and was not reached in HPV-positive (HPV+) ones (95% CI 27.7-NR; P = 0.008). With regard to progression-free survival, HPV- patients reached a median of 9.2 months (95% CI 7.9-11.2 months) compared to 14.3 months (95% CI 13.8-16.4 months) when HPV was positive (P = 0.001). The overall response rate for HPV+ patients yielded 82.4% compared to 47.1% in negative ones. No differences regarding programmed death-ligand 1, VEGF, HIF1, stromal fibrosis, or immunoscore were identified.

Conclusions: In patients with HPV+ lung adenocarcinoma, a significant benefit in overall response and survival outcomes is observed.

Keywords: HPV infection; immunotherapy; lung cancer.

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Conflict of interest statement

Disclosure AFC discloses financial research support from Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Foundation Medicine, Roche Diagnostics, Thermo Fisher, Broad Institute, Amgen, Flatiron Health, Teva Pharma, Rochem Biocare, Bayer, INQBox and The Foundation for Clinical and Applied Cancer Research – FICMAC. Additionally, he was linked and has received honoraria as an advisor, participated in speakers' bureau. He gave expert testimony to EISAI, Merck Serono, Jannsen Pharmaceutical, Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Pfizer, Novartis, Celldex Therapeutics, Foundation Medicine, Eli Lilly, Guardant Health, Illumina, and Foundation for Clinical and Applied Cancer Research – FICMAC. OA reports personal fees from Pfizer, grants and individual fees from AstraZeneca, grants and individual fees from Boehringer Ingelheim, Lilly, Merck, Bristol-Myers Squibb, and Roche, outside the submitted work. CR reports relation with Mylan, Archer Biosciences, Oncopass, Inivata, Merck Serono Novartis, MSD, Boehringer Ingelheim, Guardant Health, and AstraZeneca as part of speakers' bureau. Also, he received research funding from Pfizer and had uncompensated relationships with OncoDNA, Biomark, and Guardant Health. GR discloses travel, accommodations, and expenses from AstraZeneca and Pfizer, and consulting advisory role with Roche, Amgen, and Pfizer. UM reports personal fees from Boehringer Ingelheim, AstraZeneca, Roche, MSD, Amgen, Merck, and BMS for participation in a speaker bureau; personal fees from Boehringer Ingelheim, MSD, Amgen, Merck, and BMS for acting in an advisory role; financial support from Boehringer Ingelheim and Amgen that was paid directly to his institution outside the submitted work. All other authors have declared no conflicts of interest.

Figures

Figure 1
Figure 1
(A) Overall survival curves in ICI-treated patients according to HPV status (n = 62). (B) Progression-free survival curves in ICI-treated patients according to HPV status (n = 62). HPV, human papilloma virus; ICI, immune checkpoint inhibitor.
Figure 2
Figure 2
(A) Overall survival curves based on type of response (N = 62). (B) Progression-free survival curves based on type of response (N = 62). CR, complete response; PR, partial response; PD, progressive disease; SD, stable disease.
Figure 3
Figure 3
Comparative VEGF(A) and HIF1(B) mRNA expression levels between the HPV+ and HPV− groups. HIF1, hypoxia-inducible factor 1; HPV, human papilloma virus; mRNA, messenger RNA; VEGF, vascular endothelial growth factor.
See this image and copyright information in PMC

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