The development of uterine cervical neoplasms is mostly caused by oncogenic strains of human papillomavirus (HPV) which are sexually transmitted and highly prevalent [1,2]. Roughly, 20% of infected women are diagnosed with cervical intraepithelial neoplasia (CIN). CIN classification is divided into CIN1 (mild), CIN2 (moderate), and CIN3 (severe) [3,4]. It generally takes more than a decade for CIN to progress into cervical cancer. Cervical cancer ranks as the fourth most prevalent form of cancer in women worldwide. According to statistics from 2020, cervical cancer was responsible for 604,000 newly diagnosed cases and 342,000 deaths across the world [5]. The overwhelming majority of cervical cancer cases, exceeding 90%, are linked to HPV [6,7].

Generally, HPV is responsible for most cases of cancer of the head and neck, anus, penis, cervix, oral cavity, and others [8]. This accounts for about 4.5% of all diagnosed malignant neoplasms in humans. While there are over 182 identified types of HPV, only specific types as 16 and 18 are considered major risk factors for the development of CIN and cervical cancer [9], [10], [11]. The reason for the lack of attention from doctors and society towards HPV is that most HPV infections are temporary and can be cleared by the body's immune system. However, this lack of attention may lead to a growing and deadly problem, as each new HPV infection has the potential to become a lifelong, incurable disease if left untreated. Despite significant progress in understanding the mechanisms underlying HPV pathogenesis, there is currently no successful therapy for HPV infection. Research has demonstrated that preventive vaccines have resulted in a decrease in the burden of HPV infection. Nevertheless, not all nations have implemented government-funded HPV vaccination programs to protect young individuals [12].

Traditional therapeutic approaches for managing CIN are often invasive and can be categorized into two main groups: destructive methods such as laser evaporation, cryodestruction, and diathermocoagulation that are aimed at eradicating the abnormal tissue, and pathological tissue removal techniques that involve laser, electrosurgical, or surgical excision. While various treatment methods, such as cryosurgery, large loop excision of the transformation zone, cold-knife excision, laser ablation, and electrocautery have demonstrated high success rates, there is no consensus on the best approach for managing CIN [13], [14], [15]. The most prevalent side effects of these treatments include hemorrhage, damage to underlying tissues resulting in the formation of rough surfaces, and stenosis or constriction of the cervical canal. Alterations in the anatomy of the cervix uteri can result in functionality loss. This can cause a decrease in cervical secretions, which in turn can reduce the likelihood of conception, increase the risk of spontaneous abortion, lead to a rise in perinatal mortality, and hinder normal delivery [16], [17], [18]. Undoubtedly, finding the most effective way to manage CIN demands the exploration and implementation of new therapeutic approaches while preserving the functional integrity of the affected organ. Thus, one potential solution that can fulfill these criteria is Photodynamic Therapy (PDT).

PDT is a treatment approach that is non-invasive or minimally invasive and has demonstrated potential in the management of cervical neoplasia. PDT is a treatment method that employs a photosensitizer (PS) to selectively kill cells, often cancer cells, by activating them inside the body using laser light [19]. The use of various photosensitizers that are selective towards specific tissues combined with laser irradiation that is focused on the lesion area and the short half-life of the cytotoxic species generated in the process helps ensure that the phototoxic damage is primarily restricted to the lesion, sparing normal surrounding tissues. As a result, PDT causes less damage to normal tissues than conventional treatments such as surgery, radiation therapy, or chemotherapy, and thus, represents a promising alternative therapeutic approach for managing CIN [20,21]. Moreover, PDT can stimulate the human innate immune system, which in turn may be salutary in the treatment of HPV infections [22,23].

Although the effects of PDT have been studied since the end of the last century, its impact on CIN is still not widely and accurately understood. Several systematic reviews have already investigated the safety and efficacy of PDT for CIN and found positive trends. However, to date, many of the papers included in the reviews have relatively outdated data [21,24].

We are investigating the following questions: what is the overall effectiveness and safety profile of PDT in the treatment of precancerous lesions of the cervix associated with HPV compared to other treatments or placebo? What is the long-term effectiveness of it? Are there any differences in the effectiveness or safety of photodynamic therapy in subgroups of patients based on factors such as age, HPV status, severity of precancerous lesions, treatment dosage, or treatment duration?

The study aims to evaluate the effectiveness and safety of PDT in the treatment of precancerous diseases of the cervix associated with human papillomavirus (HPV).