Discussion:
This systematic review reported 15 studies totally involving 612 patients with LP treated with CO2 laser or KTP laser and 2120 surgeries, including 102 KTP cases from 5 studies and 510 CO2 cases from 10 studies separately. Both CO2 and KTP groups were improved postoperatively in clinical outcomes. Compared with the CO2 group, the KTP group showed significantly better results in cure rate and had a lower postoperative complication rate. To the best of our knowledge, this work is the first study that systematically and comprehensively compares the clinical outcomes of CO2 and KTP lasers for LP.
Although LP is a benign disease as mentioned above, it is frequently associated with substantial morbidity and mortality4. Therefore, balancing treatment goals (voice preservation and disease regression and/or restoration) with the morbidity and cost of the treatment is required and should be seriously considered before treatments7. Recent studies have found that Human papillomavirus (HPV, a DNA virus) is the cause of LP. Besides, pieces of evidence suggested that more than 100 genotypes of HPV infecting exist45–47. For instance,HPV-6 and HPV-11 result in the low-risk and the most common LP; HPV-16 and HPV-18 play a high-risk role but rarely happen48. According to clinical cases observed, two categories are divided depending on onset age. Juvenile onset RRP (JoRRP) represents the onset age of patients less than 12 years old, while adult-onset RRP (AoRRP) more than 12 years old5,8. Most JoRRP is transmitted vertically during pregnancy or acquired from a contaminated mother during delivering; as for AoRRP, it is often sexually transmitted by oral sex49. Besides, a trimodal distribution has been pointed out that 7, 35, and 64 years old are the peaking onset ages50. In spite of this, a bimodal distribution is most acceptable by researchers5,49,51. Based on the information, a serial of anti-viral drugs was investigated for LP, including the HPV vaccine, Interferon, Cidofovir, Bevacizumab, Celecoxib, and so forth5,52. For instance, the meta-analysis of Rosenberg et al. found that the number of surgeries/months was significantly reduced after long-term HPV vaccination than before vaccination53. These adjuvant treatments may benefit patients with LP treated with surgical excision and more studies are needed to assess the effects of combination KTP laser surgery with adjuvant therapies.
In this review, we found that both KTP and CO2 laser groups demonstrated satisfactory outcomes for LP in the cure rate, 87.25% and 75.98% respectively. In addition, the cure rate of KTP laser is significantly higher than that of CO2 laser, which demonstrated the main therapeutic effect of KTP laser is superior. Another evaluation indicator is recurrence rate, but we found there no difference between the two groups for LP treatment (9.8% vs 10%, p=0.2967). Moreover, the safety outcome-complication rate of the KTP group is 2.32%, which is considerably lower than that of CO2 laser (17.71%) (p<0.0001). Those findings strongly support our hypothesis that KTP laser could yield comparatively better outcomes than CO2 laser for LP.
Several reasons may explain why KTP laser was superior to CO2 laser for LP according to literature. The CO2 laser was firstly used in the 1960s and it quickly gained popularity for LP14,18. Many therapeutic options have been advocated for LP, such as microblade and PDL laser, but surgical removal using CO2 laser remains the most important single treatment choice4,54,55. Although the 10 600 nm wavelength of the CO2 laser is well absorbed by water in biological tissue and is suitable for fine surgical cutting, its application to remove laryngeal lesions is not without risk56,57. Thermal injury, excessive resection, and repeated surgeries may result in a loss of pliable vocal fold tissue, fibrosis, and scar formation, which can significantly affect the quality of voice and life34,58.
As for KTP laser, it has both the cutting function of CO2 laser and the hemostatic effect of PDL laser, so its application in laryngeal microsurgery has many advantages: (1) The operation is significantly less destructive than the traditional laryngeal laceration, without laryngeal laceration, and with less tracheotomy ratio. In addition, KTP laser is more likely to preserve postoperative laryngeal function, and the postoperative hospital stay was short (less cost), requiring only 2 to 3 days44. (2) The accuracy and precision of the operation were improved by using a KTP laser. The tumor boundary can be clearly seen under the microscope, and the level of incision can be distinguished so that the lesion can be completely removed while minimizing collateral damage59. (3) The fiber-based delivery of the KTP laser with the technical advancement of distal-tip endoscopy enables surgical procedures to be performed in-office settings under local anesthesia, by which considerable time and medical expenses would be saved31,35. (4) The KTP laser has a good hemostatic effect and allows the surgery to be performed in a bloodless manner. Especially in children with laryngeal papilloma invading the supraglottis, the tumor has a rich blood supply. Under this condition, the KTP laser can be applied to its advantage, resulting in a clear field and a well-defined cut, reducing collateral damage5,53.
This study had several limitations. Firstly, the available studies or data about KTP laser used for LP were very limited (102 patients). Whereas the cases number achieved the minimal sample number after conducting a sample size estimation (58 in each group). Secondly, much data collected by different studies are not consistent between KTP and CO2 groups. For example, HPV positive rate, remission rate, and clearance rate for LP were always presented in the CO2 group but rarely appeared in the KTP group1,40, which made it impossible to compare those parameters and may potentially influence the results of this study. We recommend that future studies should report those data for patients with LP as possible. In addition, the age difference (before surgery) between CO2 group and KTP group should be noted. But we believe due to most studies in CO2 group did not report the detail age of patients (419/510 patients), the data of age from the two groups was not representative and the difference should not be a serious problem. Thirdly, high-quality comparative evidence is significantly insufficient as most studies included were at level D. The MINORS scores of these studies averaged 13.1 and 13.6 in the CO2 group and KTP group, respectively, demonstrated the fair quality of evidence. Future research in the form of standard-evaluation prospective multicenter randomized controlled studies is required.