Table 2.

A summarized description of all the included studies in this review.

Author, Year	Study Type	Sample	Laser	Method of Evaluation	Main Outcomes	Conclusions	PBM Effect
1. Sroka et al., 1999 [11]	In vitro	Human SCC 1 of gingival mucosa (ZMK1) and other human cells	Different lasers; 410, 488, 630, 635, 640, 805, and 1064 nm	Mitosis rate by orcein-staining and cell proliferation by BrdU-test	A slight decrease in the mitotic rate of ZMK1 was observed with the increase in the irradiation energy independently with the wavelength. At irradiation of 20 J/cm2, a slight decrease in mitosis rate was observed when compared to controls without dependence on wavelength.	At specific parameters, an inhibitory effect of PBM was observed on human SCC when compared to controls.	Inhibitory
2. de Castro et al., 2005 [22]	In vitro	KB cells	Diode lasers 685 and 830 nm	Cellular viability by MTT spectroscopy assay	The time significantly influenced the cellular viability in both control and test groups (for both wavelengths). The PBM in both test groups significantly influenced the cellular viability when compared to control. The test group irradiated with 830 nm showed a significant increase in proliferation when compared to the other test group (685 nm).	PBM had a significant bio-stimulatory effect on KB cells proliferation influenced by the wavelength.	Stimulatory
3. Frigo et al., 2009 [23]	In vitro/In vivo	Melanoma cells (B16F10)/Melanoma cells in mouse model	InGaAlAsP 2 laser 660 nm	In vitro: cell viability and cell cycle changes by Tripan Blue, MTT, and cell quest histogram. In vivo: tumor volume and histological characteristics.	In vitro: The high irradiance (2.5 W/cm2) combined with high dose (1050 J/cm2) stimulated melanoma tumor growth. In vivo: A significant increase in the tumor volume, blood vessels and cell abnormalities was observed in the group of does 1050 J/cm2.	PBM over melanoma showed a stimulative effect and increase in tumor growth when applied in high irradiance and dose.	Stimulatory
4. de C Monteiro et al., 2011 [24]	In vivo	Cancerous lesions on hamster’s cheek induced by chemical carcinogenesis	Diode laser 660 nm	Histological analysis	The test group (with PBM) showed a significant difference in the amount of poorly differentiated tumors when compared to other groups without PBM.	PBM with these parameters may cause a progression of the severity of oral SCC in hamsters.	Stimulatory
5. Myakishev-Rempel et al., 2012 [25]	In vivo	SKH mouse nonmelanoma UV 3-induced skin cancer model	NASA LED 4 670 nm	Photographic measurements of tumor growth	PBM didn’t show a measurable effect on tumor growth.	PBM with these parameters may be safe in case of application in presence of malignant lesions.	Inhibitory
6. Schartinger et al., 2012 [26]	In vitro	Human SCC cells (SCC25) and human normal cells	GaAlAs 5 660 nm	Cell proliferation assay by MTT, cell cycle analysis, and apoptosis assay	In SCC25 cells, PBM showed a significant decrease in cell proliferation and in the percentage of G1-phase cells, and a significant increase in the percentage of S-phase cells when compared to the control. PBM showed a proapoptotic effect in SCC25.	PBM with these parameters did not show a stimulative effect.	Inhibitory
7. Sperandio et al., 2013 [12]	In vitro	Oral dysplastic cells (DOK) and oral cancer cells (SCC9 and SCC25)	GaAlAs laser 660 nm and 780 nm	Cellular viability by 3-h MTS assay, the apoptosis rate by TUNEL assay, and proteins analysis by Western blot and immunofluorescence	In SCC9, PBM showed inhibition of growth with 660 nm and stimulative effect with 780 nm. In SCC25, PBM showed a stimulative effect with both wavelengths. At 72 h evaluation time, PBM showed the lower levels of stimulation. PBM showed an effect on proteins and in particular caused an increased expression of p-Akt 6, pS6 and cyclin D1 proteins producing an aggressive isoform of Hsp90. Only SCC25 showed apoptosis when irradiated with 780 nm at 48 h (6.15 J/cm2) and at 72 h (3.07 J/cm2).	PBM with these parameters can aggravate oral cancer cellular behavior and modify the expression of proteins related to the progression and invasion of cancer cells.	Stimulatory
8. Gomes Henriques et al., 2014 [27]	In vitro	Human SCC of tongue (SCC25)	InGaAlP 7 laser 660	Cell growth assay, cell invasion analysis by Matrigel assay, and protein expression analysis	PBM on SCC25 with energy density of 1.0 J/cm2 showed a significant increase in proliferation, and expression of cyclin D1 and nuclear β-catenin, and a promotion of invasion through the reduction of E-cadherin and induction of MMP-9 8 expression.	PBM stimulated the proliferation and invasion of SCC25 and caused alterations on proteins expression.	Stimulatory
9. Ottaviani et al., 2016 [18]	In vitro/In vivo	In vitro: Mouse melanoma cells (B16F10) and other human cells In vivo: Oral carcinogenesis model with 4-NQO 9 on mouse tongue	GaAs 10 and InGaAlAsP lasers 660, 800, and 970 nm	In vitro: ATP production assay In vivo: Histological evaluation and Immunofluorescence, real time PCR 11 and Flow Cytometry	In vitro: PBM showed an increase in cellular metabolism. In vivo: PBM reduced the tumor progression and this was associated with secretion of type I interferons from T lymphocytes and dendritic cells. A decrease in the angiogenic macrophages was observed in the tumor mass with a promotion of the vessel’s normalization.	PBM reduced tumor growth and was a safe procedure.	Inhibitory
10. Rhee et al., 2016 [28]	In vivo	Anaplastic thyroid cancer cell line FRO in mouse model	Diode laser 650 nm	Tumor volume, histological evaluation, and IHC 12 staining analysis	PBM caused an elevation of HIF-1α 13 and p-Akt, and a decrease in TGF-β1 14 expression that play a role in the cell cycle regulation.	These effects may cause an over-proliferation and angiogenesis of cancer cells. PBM may cause aggressiveness of cancer through TGF-β1 and Akt/HIF-1α cascades.	Stimulatory
11. Takemoto et al., 2019 [29]	In vitro	Human SCC cell line (CAL27) seeded over normal stromal gingival fibroblasts	LED 660 nm	Expansion of colonies and cell counts, viability and apoptosis after PBM with 36 J/cm2	After 72 h of treatment, PBM inhibited the expansion of colonies. At high dose (36 J/cm2), PBM showed a general advantage with regard to the cell viability, apoptosis, and death assays on the stromal fibroblasts over cancer cells.	PBM (LED) at high doses inhibited in vitro the progression and number of cancer cells colonies without affecting the surrounding fibroblasts.	Inhibitory
12. Shirazian et al., 2020 [30]	In vitro	SCC cells originated from tongue (TSCC-1)	Diode lasers 660 and 810 nm	Cell proliferation by MTT assay, and flow cytometry to assess cyclin D1, β-catenin, E-cadherin, and MMP-9 markers. RT-PCR 15 to assess Ki67 and VEGF 16 expression levels	At 24 h evaluation, the cell proliferation was generally lower in PBM groups. In 810 nm groups (100 and 200 mW), higher percentages of cyclin D1and MMP-9 were observed, and a significant decrease in VEGF marker in the 810 nm group of 200 mW. In 660 nm groups (40 and 80 mW), higher percentages of β-catenin and E-cadherin were observed. No differences were observed among groups for the Ki67 marker.	PBM with 660 nm (80 mW) and 810 nm (200 mW) showed a significant inhibitory effect on cell proliferation at 0 and 24 h.	Inhibitory

¹ Squamous Cell Carcinoma (SCC); ² Indium–Gallium–Alluminium-Arsenide Phosphide (InGaAlAsP); ³ Ultraviolet (UV); ⁴ Light-Emitting Diode (LED); ⁵ Gallium Aluminium Arsenide (GaAlAs); ⁶ phospho Akt (p-Akt); ⁷ Indium–Gallium–Aluminum Phosphide (InGaAlP); ⁸ Matrix Metallopeptidase-9 (MMP-9); ⁹ 4-nitroquinoline-1-oxide (4-NQO); ¹⁰ Gallium Arsenide (GaAs); ¹¹ Polymerase Chain Reaction (PCR); ¹² Immunohistochemical (IHC); ¹³ Hypoxia Inducible Factor-1α (HIF-1α); ¹⁴ Transforming Growth Factor-β1 (TGF-β1); ¹⁵ Real-Time Polymerase Chain Reaction (RT-PCR); ¹⁶ Vascular Endothelial Growth Factor (VEGF).