Proliferative verrucous leukoplakia and its tumor markers: Systematic review and meta‐analysis

Abstract

Background The aim was to update information on oral proliferative verrucous leukoplakia (PVL), a disease of verrucous‐like lesions with high risk of malignancy, and its biomarkers. Methods A systematic search of literature on PVL and its biomarkers showed 22 biomarkers that were investigated in 19 papers. A meta‐analysis was possible for human papillomavirus (HPV), aneuploidy, Ki‐67, and p53. Results Aneuploidy was found consistently (I2 = 0%, P = 0.61) in 92% (95% CI 80%‐99%) of the PVL cases. P53 positivity prevalence was 27% (95% CI 15%‐40%) in two available studies (I2 = 0%, P = 0.64). With HPV and Ki‐67, the most outlying studies needed to be removed and after that the pooled HPV positivity prevalence (I2 = 24%, P = 0.27) was 5% (95% CI 0%‐14%) and for Ki‐67 (I2 = 9%, P = 0.33) 14% (95% CI 6%‐26%). Conclusions With the evidence of the current literature, aneuploidy could value as a biomarker of PVL but should be further validated.

Aneuploidy and loss of heterozygosity as risk markers for malignant transformation in oral mucosa

“…However, difficulties in definitively diagnosing lichen planus from other OPMD may account for apparently excessive rates of aneuploidy reported in some studies (Femiano & Scully, 2015;Mattila et al, 2004) that appear inconsistent with the extremely low transformation rate in lichen planus. The predictive value of DNA ploidy analysis in proliferative verrucous leukoplakia appears similar to that determined for other OPMD (Gouvea et al, 2013;Kahn et al, 1994;Klanrit et al, 2007), and is supported by meta-analysis (Rintala et al, 2019), though data are very limited (Okoturo et al, 2018). A single study suggests DNA ploidy is also predictive for precursor lesions in Fanconi anaemia (Velleuer et al, 2020).…”

Lichenoid morphology could be an early feature of oral proliferative verrucous leukoplakia

“…Only a limited number of biomarkers have so far been investigated in PVL: P53 positivity was 27% (95% CI 15%‐40%) in two published studies 27 . Ploidy analysis of mucosal biopsies have recently shown promise in the risk stratification of an OPMD 28,29 .…”

Morphological Changes of the Endometrium in Hyperplastic Process in Women of Reproductive Age

“…Viruses are known to promote the development of tumors in both humans and animals, and HVI, for example, is known to frequently infect the ectocervical epithelium and is closely associated with the development of cervical cancer [23]. It became known that the virus is involved in the pathogenesis of endometrial hyperplasia [25]. It is likely that it exists in epitheliocytes not only as a "passenger", but also as an etiological factor.…”

“…A recent study showed that the herpes virus and HVI in endometrial biopsy persist in 40.7% of women with chronic endometritis, microbial viral associations -in 35% [20][21][22][23]. Some researchers have demonstrated the possible involvement of viral infection in the occurrence of atypia in HPE, in particular, reports of the presence of HPV in adenocarcinomas of endometrial tissue have been published [16,[24][25][26][27]. However, diseases caused by HVI in the female genitals are usually associated with specific areas: the vulva, vagina, cervix and uterine body, where there is a specific epithelium-stratified squamous cell, leading to epithelial cell proliferation and often to atypia.…”

“…In contrast to the molecular diversity of microbes, morphological manifestations of tissue reactions to microorganisms, as well as morphogenetic mechanisms of these changes are often pathognomonic for a particular microorganism, which should certainly be considered in histological diagnosis. The question arises whether morphological changes can be detected in any tissues, indicating, for example, HPI [10,25,28].…”