Oral potentially malignant disorders (OPMD) are a group of conditions that may progress to oral cancer however as the descriptor implies, the progression to malignancy is only a potential risk. The term recognises that even in patients with a defined lesion (e.g. leukoplakia), malignancy may arise elsewhere in the oral cavity as a result of field change, even in clinically normal mucosa.¹ The term OPMD was introduced in 2007 after an expert group meeting coordinated by the World Health Organisation (WHO) and is currently included in the 4th edition of the WHO classification for Head and Neck Tumours (table 1).^{2, 3}

• Erythroplakia
• Erythroleukoplakia
• Oral Submucous fibrosis
• Dyskeratosis congenita
• Smokeless tobacco keratosis
• Palatal lesions associated with reverse smoking
• Chronic candidiasis
• Lichen planus

Human Papilloma Virus (HPV) is a recognised risk factor for head and neck cancers and these HPV positive cancers have different clinical and biological characteristics in comparison to HPV negative head and neck cancers. ⁴ However, the role of HPV in OPMD is less well known. The authors of this systematic review and meta-analysis aimed to provide estimates of HPV prevalence in OPMD and evaluate the impact of the presence of epithelial dysplasia.

Methods

This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Searches were conducted in PubMed, Embase and the Cochrane Library databases using relevant keywords (OPMD and its subtypes, including some as outlined in table 1). The review included searches for peer-reviewed studies that examined the prevalence of HPV DNA in OPMD. At least five cases were needed for inclusion. If participants represented a group of immunocompromised patients, then the study was excluded. Histopathological diagnosis of OPMD was required as was HPV DNA detection through polymerase chain reaction in tissue samples or cell samples for inclusion. HPV DNA samples in saliva, gargle or serum were excluded. Risk of Bias was assessed through discussion by two of the authors. Sensitivity analyses was performed on studies that included a health control. The parameters used for quality assessment included stratification of type of tissue, type of biopsy, type of PCR primer and year of publication.

Results

• 2,113 studies were initially identified and 52 papers with a total of 2,677 cases were included in the review.
• The majority of studies originated from Asia and Europe. The OPMD subgroups assessed in most studies were leukoplakia and lichen planus while few reported erythroplakia, oral submucous fibrosis, proliferative verrucous leukoplakia and OPMD unspecified samples.
• The overall pooled prevalence of HPV in OPMD (based on all 52 studies) was 22.5% (95% CI 16.6-29.0) with large between study heterogeneity (I2=93%).
• The HPV prevalence different according to continent, ranging from 16.5% (95% CI 8.3-26.7) in Asia and 46.8% (95% CI 29.2-64.8) in samples from South America. HPV prevalence was similar in different OPMD subgroups.
• Information on epithelial dysplasia was available in 19 studies. The pooled HPV prevalence did not vary much between non-dysplastic (514 cases, 23.8%, 95% CI 10.5– 40.4) and dysplastic samples (418 cases, 19.0%, 95% CI 9.5–31.0)
• Among HPV-positive OPMD cases, HPV16 was the most prevalent genotype with a pooled prevalence of 48.2% (95% CI 31.4–65.2), followed by HPV18 (36.2%, 95% CI 16.7–58.5).
• The sensitivity analysis in the present meta-analysis restricted to these 31 studies revealed a pooled HPV prevalence of 27.3% (95% CI 20.3–35.0) among OPMD cases and 10.3% (95% CI 5.3–16.8) among controls.

Conclusions

The authors concluded: –

…”More than one in five OPMDs harbour HPV

• The pooled HPV prevalence appeared to be comparable across OPMD subgroups

• HPV16 was the most prevalent genotype

• The prevalence of HPV seemed independent of the presence of epithelial dysplasia….”

Comments

This systematic review and meta-analysis provides insight into the role of HPV in OPMD and explores the possible link of oral cancer development with HPV infection. However, one in five OPMDs being HPV positive is not a substantial link however as the authors mention, the results of this systematic review and meta-analysis need to be interpreted with caution given the heterogeneity between included studies. Moreover, there was no risk of bias assessment performed of included studies. The presence of HPV was detected independent to the presence of epithelial dysplasia therefore, there may be multiple mechanisms responsible for the development of HPV positive and negative OPMD.

Links

Primary paper

de la Cour CD, Sperling CD, Belmonte F, Syrjänen S, Kjaer SK. Human papillomavirus prevalence in oral potentially malignant disorders: Systematic review and meta-analysis [published online ahead of print, 2020 Mar 6]. Oral Dis. 2020;10.1111/odi.13322. doi:10.1111/odi.13322

Other references

1. Speight PM, Khurram SA, Kujan O. Oral potentially malignant disorders: risk of progression to malignancy. Oral Surg Oral Med Oral Pathol Oral Radiol. 2018;125(6):612-27.

2. Warnakulasuriya S. Oral potentially malignant disorders: A comprehensive review on clinical aspects and management. Oral Oncology. 2020;102:104550.

3. El-Naggar AK, Chan JKC, Grandis JR, Slootweg PJ. WHO Classification of Head and Neck Tumours: World Health Organization; 2017.

4. Sathish N, Wang X, Yuan Y. Human Papillomavirus (HPV)-associated Oral Cancers and Treatment Strategies. Journal of dental research. 2014;93(7 Suppl):29S-36S.

Picture Credits

“Human Papilloma Virus” by National Institutes of Health (NIH) is licensed under CC BY-NC 2.0