Lasers in Medical Science

The role of photodynamic therapy in treating LSIL in women with high-risk HPV: a literature review

Photodynamic therapy has become a promising non-invasive method for the treatment of LSIL associated with HR-HPV infections. This literature review assesses the efficacy, safety, and clinical relevance of PDT for managing HPV-related cervical lesions. PDT employs photosensitizers, such as 5-aminolevulinic acid, which selectively accumulate in abnormal cervical tissues. When subjected to particular wavelengths of light, these agents become activated and produce reactive oxygen species, leading to the target elimination of particular cells. Numerous studies have documented the effectiveness of PDT with pathological regression rate improving to 94.79%, and the HR-HPV clearance rate increased to 93.75%. Beyond facilitating lesion regression, PDT also plays a significant role in eliminating persistent HR-HPV infections, which are a crucial element in the advancement of cervical dysplasia. Furthermore, the non-invasive nature of PDT presents a compelling alternative to traditional surgical approaches, which may compromise fertility and cause cervical stenosis. PDT is generally well-tolerated; adverse reactions are typically mild and transient, including symptoms such as abdominal discomfort and increased vaginal discharge. Most notably, the fertility-preserving characteristics of PDT render it an optimal treatment choice, particularly for young women desiring to maintain their reproductive potential. While the existing data is promising, it is essential to conduct additional research to enhance treatment protocols, optimize dosages, and thoroughly assess the long-lasting impact of photodynamic therapy in the field of gynecology. By synthesizing existing evidence, this review supports the enhanced incorporation of PDT into clinical decision-making frameworks for the management of HPV-related LSIL.

Rapid diagnosis of cervical cancer based on serum FTIR spectroscopy and support vector machines

Cervical cancer is one of the most common malignant tumors among female gynecological diseases. This paper aims to explore the feasibility of utilizing serum Fourier Transform Infrared (FTIR) spectroscopy, combined with machine learning and deep learning algorithms, to efficiently differentiate between healthy individuals, hysteromyoma patients, and cervical cancer patients. In this study, serum samples from 30 groups of hysteromyoma, 36 groups of cervical cancer, and 30 healthy groups were collected and FTIR spectra of each group were recorded. In addition, the raw datasets were averaged according to the number of scans to obtain an average dataset, and the raw datasets were spectrally enhanced to obtain an augmentation dataset, resulting in a total of three sets of data with sizes of 258, 96, and 1806, respectively. Then, the hyperparameters in the four kernel functions of the Support Vector Machine (SVM) model were optimized by grid search and leave-one-out (LOO) cross-validation. The resulting SVM models achieved recognition accuracies ranging from 85.0% to 100.0% on the test set. Furthermore, a one-dimensional convolutional neural network (1D-CNN) demonstrated a recognition accuracy of 75.0% to 90.0% on the test set. It can be concluded that the use of serum FTIR spectroscopy combined with the SVM algorithm for the diagnosis of cervical cancer has important medical significance.

Combination of cisplatin treatment and photodynamic therapy attenuates cisplatin-induced cell toxicity in A2780 and A2780-CP cervical cancer cell lines

Cervical cancer is recognized as a serious worldwide health problem. Despite various achievements for cervical cancer treatment, there are still shortcomings that lead to severe side effects. Combination therapy is fast becoming a key and promising treatment strategy, diminishing chemotherapy-mediated side effects. The objective of this study was to determine the effect of combined cisplatin treatment and photodynamic therapy (PDT) on the cervical cancer recovery. In this study, A2780 and A2780-CP cell lines were cultured in the Dulbecco's modified eagle medium (DMEM) enriched with 10% FBS and 1% antibiotic. Both cell lines were treated with cisplatin, photodynamic light (laser with methylene blue as a photosensitizer agent), and the combination of cisplatin treatment and PDT. Half maximum inhibitory concentration (IC50) was calculated for each treatment by the use of tetrazolium salt assay. Both cell lines were examined for cell membrane lipid peroxidation rate. Our findings showed that combination of cisplatin treatment and photodynamic therapy leads to two-fold decreased cisplatin IC50. Results showed that cisplatin and photodynamic light combination could effectively reduce A2780 and A2780-CP cell viability (p-value < 0.0001). Moreover, combined cisplatin and photodynamic therapy results revealed significantly increased cancer cell membrane destruction through increased lipid peroxidation, resulting in surged MDA content. Our conclusion is that combination of cisplatin and photodynamic therapy can be used as an effective and convenient treatment strategy without considerable side effects.

Advanced methylene blue — nanoemulsions for in vitro photodynamic therapy on oral and cervical human carcinoma

Photodynamic therapy (PDT) is a therapeutic modality with high contributions in the treatment of cancer. This approach is based on photophysical principles, which presents as a less invasive strategy than conventional therapies. Combined with nanotechnology, the therapy becomes more efficient because nanoparticles (NPs) have advantageous characteristics such as biocompatibility, controlled, and targeted release, promoting solubility and decreasing the toxicity and side effects involved. In this work were developed nanoemulsions containing the methylene blue photosensitizer (MB) (MB/NE) and in the empty form (unloaded/NE). Subsequently, the mentioned nanomaterials were characterized by the measurement of dynamic light scattering (DLS). The MB/NE and unloaded/NE showed appropriate physical and chemical characteristics, with particle size ≤ 200 nm, polydispersity index close to 0.3, and zeta potential exhibiting negative charge, showing stable values during the analysis. The incorporation of the MB did not cause changes in the photophysical profile of the photosensitizer. The quantification performed showed an incorporation rate of 81.9%. Viability studies showed an absence of cytotoxicity for MB/NE in the concentrations of 10-75 µmol·L

Comment on “Raman spectroscopy combined with multivariate statistical algorithms for the simultaneous screening of cervical and breast cancers”

This article discusses current research on the detection of cervical and breast cancer using in vitro Raman spectral analysis of human serum by Cao et al. (2024) which was published in the Lasers in Medical Science journal. Despite the high accuracy of the suggested approach (93%), the demonstrated findings could be treated unclear due to possible overestimation of the classification models.

Study on the mechanism of photodynamic therapy mediated by 5-aminoketovalerate in human ovarian cancer cell line

We aimed to investigate the mechanism and effect of photodynamic treatment mediated by 5-aminoketovalerate (5-ALA-PDT) on human ovarian cancer cells (OVCAR3 cells) and to provide a theoretical basis for the subsequent experimental step in vivo. Human ovarian cancer OVCAR3 cells were randomly divided into four groups: control group, laser irradiation alone group, photosensitizer alone group, and photodynamic treatment group. Alterations in cell morphology were observed with an inverted light microscope; cell viability was examined by CCK-8 assays. The ROS content and apoptosis rate were examined by flow cytometry analysis. Western blot was used to detect the expression of apoptosis-related proteins, such as caspase-3, Bax, and Bcl-2, and the expression of cleaved caspase-3 in live cells was detected by a cleaved caspase-3 assay kit. Inverted light microscopy showed alterations in cell morphology in different stages. Comparison with the three other groups indicated that tumor cell proliferation was significantly decreased in the photodynamic treatment group (P < 0.05). Flow cytometry analysis revealed that the content of ROS was higher in the photodynamic group than in the other three groups, and the apoptosis rate was higher in the photodynamic treatment group. The difference compared with the other three groups was statistically significant (P < 0.001). The western blot results indicated that the protein expression of Bcl-2 and caspase-3 was decreased in the photodynamic treatment group, and the protein expression level of Bax was increased (P < 0.05). The expression of cleaved caspase-3 was increased in the photodynamic treatment group compared with the other groups according to the data obtained with a microplate reader. Thus, our results demonstrated that the apoptosis and viability of OVCAR3 cells are altered in response to 5-ALA-PDT; however, no remarkable effects were observed in ovarian cancer cells treated with laser irradiation or photosensitizer alone. 5-ALA-PDT can significantly inhibit the growth of human ovarian cancer cells, and the mechanism of this effect is related to the tumor cell apoptosis mediated by the downregulation of Bcl-2 and caspase-3 and upregulation of Bax protein expression.

Clinical efficacy of a new therapeutic option for lower genital tract lesions: 5-ALA photodynamic therapy

The study utilized 5-ALA-PDT to treat patients with CIN or VaIN and assessed their clinical response, HPV clearance, and influencing factors after photodynamic therapy (PDT). This study involved 56 patients who received 5-ALA-PDT in a single center from May 2020 to March 2022, including 12 patients with CIN, 30 patients with VaIN, and 14 patients with both CIN and VaIN. Follow-up were conducted within 6 and 12 months after treatment to evaluate the clinical effectiveness of PDT. The assessment criteria included histological response (ER, elimination rate, RR, regression rate) and HPV clearance. Additionally, factors that could potentially influence the outcomes were analyzed. After PDT, the histological response showed an ER of 48.2% (27/56) and a RR of 80.4% (45/56) within 6 months of follow-up. The elimination rate increased to 69.6% (39/56) within 12 months, along with a regression rate of 82.1% (46/56). The rates of HPV clearance were observed to be 37.5% (21/56) and 44.6% (25/56) within 6 and 12 months, respectively. The study also revealed that HPV clearance significantly influenced histologic elimination within 6 months (p < 0.001) and histologic regression within 12 months (p < 0.01). Furthermore, premenopausal women exhibited a higher HPV clearance rate compared to postmenopausal women (61.5% vs. 30.0%, p = 0.036). 5-ALA PDT can be considered as an available option for the treatment of lower genital squamous intraepithelial lesions. The efficacy of its histologic response depends on HPV clearance. Additionally, it has been found that premenopausal women may benefit more from this treatment.

CO2 laser colposcopic guided surgery for the see and treat management of VHSIL: a preliminary experience

Abstract The purpose of this study is to evaluate the efficiency of CO2 laser colposcopic guided surgery performed in an outpatient see and treat setting in the management of VHSIL. Women with a suspected diagnosis of VHSIL and no vulvoscopic suspicion of vSCC were enrolled. An electronic register of CO2 laser treatment was created where description of performing parameters (excision or ablation) was specified and personal history was recorded. Statistical analysis was performed by Fisher’s exact test. Relative risks (RR) of risk factor were calculated and expressed in odds. From September 2014 to September 2018, we enrolled a total of 63 patients who underwent CO2 laser procedure and had a minimum follow-up time of 2 years at Careggi University Hospital in Florence. Forty-eight (76.2%) patients underwent laser excision and 15 (23.8%) patients underwent ablative treatment without histological results. Undertreatment was performed in 3 cases (6.3%) with definitive histology of vSCC. Therapeutical appropriateness of CO2 laser excision was reached in 85.4% of the cases (41/48). No volunteer loss to follow-up was registered; thus, fidelity to treatment was assess at 100%. Recurrence rate within 2 years attested in 8/60 followed patients (13.3%). No personal factor was found to influence the VHSIL course. CO2 laser excision may represent an excellent therapeutic option to VHSIL because it provides adequate oncological purpose with good cosmetic and functional results and high patients’ loyalty to treatment. An expert team could allow to undergo patients with VHSIL suspicion to unique diagnostic and therapeutic procedure with significant benefits.

A comparative study of 5-aminolevulinic acid photodynamic therapy and loop electrosurgical excision procedure in the treatment of cervical high grade squamous intraepithelial lesions

To compare the efficacy and safety of 5-Aminolevulinic Acid Photodynamic Therapy (5-ALA-PDT) and Loop Electrosurgical Excision Procedure (LEEP) in the treatment of cervical high grade squamous intraepithelial lesions (HSIL). The data of 116 patients with pathologically diagnosed cervical HSIL in Hangzhou First People's Hospital from January 2020 to June 2023 were retrospectively analyzed. According to the treatment methods, they were divided into 5-ALA-PDT group (50 cases) and LEEP group (66 cases). The patients were followed up at 3 months, 6 months, and 12 months after treatment. The clinical data of the two groups were compared. There were no significant differences in baseline data between the two groups of patients (P > 0.05). At 12-month follow-up the complete remission (CR) rate of LEEP group and 5-ALA-PDT group was 93.94% (62/66) and 86.00% (43/50) (P = 0.260), respectively. The HPV clearance rate of LEEP group and 5-ALA-PDT group was 66.67% (44/66) and 80.00% (40/50) (P = 0.112), respectively. Multivariate analysis revealed that endocervical canal involvement was a significant risk factor for 5-ALA-PDT failure (OR = 27.35, 95% CI: 3.512-43.390, P = 0.012) and persistent HPV infection (OR = 8.013, 95% CI: 2.045-36.901, P = 0.011). In terms of adverse reactions, most of the reactions in 5-ALA-PDT group were mild local reactions that could be relieved within one week. The proportion of bleeding and cervical scar formation was higher in patients in the LEEP group (P < 0.05). 5-ALA-PDT and LEEP exhibit potential similarity in efficacy in the treatment of cervical HSIL, but the former has milder adverse reactions. The involvement of the endocervical canal is a significant risk factor for both 5-ALA-PDT failure and persistent HPV infection.

Raman spectroscopic study of cervical precancerous lesions and cervical cancer

AbstractEarly detection of cervical lesions, accurate diagnosis of cervical lesions, and timely and effective therapy can effectively avoid the occurrence of cervical cancer or improve the survival rate of patients. In this paper, the spectra of tissue sections of cervical inflammation (n = 60), CIN (cervical intraepithelial neoplasia) I (n = 30), CIN II (n = 30), CIN III (n = 30), cervical squamous cell carcinoma (n = 30), and cervical adenocarcinoma (n = 30) were collected by a confocal Raman micro-spectrometer (LabRAM HR Evolution, Horiba France SAS, Villeneuve d’Ascq, France). The Raman spectra of six kinds of cervical tissues were analyzed, the dominant Raman peaks of different kinds of tissues were summarized, and the differences in chemical composition between the six tissue samples were compared. An independent sample t test (p ≤ 0.05) was used to analyze the difference of average relative intensity of Raman spectra of six types of cervical tissues. The difference of relative intensity of Raman spectra of six kinds of tissues can reflect the difference of biochemical components in six kinds of tissues and the characteristic of biochemical components in different kinds of tissues. The classification models of cervical inflammation, CIN I, CIN II, CIN III, cervical squamous cell carcinoma, and cervical adenocarcinoma were established by using a support vector machine (SVM) algorithm. Six types of cervical tissues were classified and identified with an overall diagnostic accuracy of 85.7%. This study laid a foundation for the application of Raman spectroscopy in the clinical diagnosis of cervical precancerous lesions and cervical cancer.

Raman spectroscopy combined with multivariate statistical algorithms for the simultaneous screening of cervical and breast cancers

Breast and cervical cancers are becoming the leading causes of death among women worldwide, but current diagnostic methods have many drawbacks, such as being time-consuming and high cost. Raman spectroscopy, as a rapid, reliable, and non-destructive spectroscopic detection technique, has achieved many breakthrough results in the screening and prognosis of various cancer tumors. Therefore, in this study, Raman spectroscopy technology was used to diagnose breast cancer and cervical cancer. A total of 225 spectra were recorded from 87 patients with cervical cancer, 60 patients with breast cancer, and 78 healthy individuals. The obvious difference in Raman spectrum between the three groups was mainly shown at 809 cm

Porphin e6 complex loaded with gold nanorod mesoporous silica enhances photodynamic therapy in ovarian cancer cells in vitro

A growing amount of experimental evidence has proven that the application of gold nanorods (AuNRs) in photodynamic therapy (PDT) can significantly enhance its therapeutic efficacy. The aim of this study was to establish a protocol for investigating the effect of gold nanorods loaded with the photosensitizer chlorin e6 (Ce6) on photodynamic therapy in the OVCAR3 human ovarian cancer cell line in vitro and to determine whether the PDT effect was different from that of Ce6 alone. OVCAR3 cells were randomly divided into three groups: the control group, Ce6-PDT group, and AuNRs@SiO

Graphene oxide-enhanced photothermal therapy: laser parameter optimization and temperature modeling for HeLa cancer cell mortality

Photothermal therapy, in which a laser is an effective tool, is a promising method for cancer treatment. Laser parameters, including power, irradiation time, type of laser radiation (continuous or chopped), and the concentration of the photothermal agent, can affect the efficiency of this method. Therefore, this study investigated and compared the effects of different laser parameters on the efficiency of photothermal treatment for cervical cancer, which is the fourth most prevalent cancer in women. In addition, we investigated the properties of graphene oxide (GO) synthesized as a photothermal agent under laser radiation, and its effectiveness in achieving the desired therapeutic temperature. This study examined and compared the effects of temperature, nanoparticle concentration, irradiation time, and laser power to understand their impact on heat transfer. The toxicity of graphene oxide at different concentrations in HeLa cancer cells was also evaluated. These results demonstrated low toxicity, particularly after 24 h, with approximately 10% toxicity. The study explored mortality under laser irradiation at various powers and time intervals using continuous and chopped beam irradiation. In addition, a model for temperature prediction using a regression tree was presented. Finally, the combined photothermal effects of graphene oxide and laser irradiation were investigated. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test results reveal significant effects, with a mortality rate of 90% in continuous radiation with a concentration of 0.3 mg/ml and 75% in chopped beam irradiation with concentrations of 0.3 and 0.4 mg/ml. A regression tree model was developed to predict temperature changes based on the GO concentration, laser power, and irradiation time, providing valuable insights for optimizing photothermal therapy parameters. Statistical analysis showed that the combined effect of graphene oxide with continuous laser irradiation was more effective than chopped-beam laser irradiation. However, the chopped-beam irradiation method is expected to cause less damage to surrounding tissues. These findings indicate that photothermal therapy with graphene oxide, chopped, and continuous laser irradiation can potently treat HeLa cancer cells and pave the way for further exploration of targeted cancer treatments.