Oral Human Papillomavirus Benign Lesions and HPV-Related Cancer in Healthy Children: A Systematic Review
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Protocol
- P—pediatric subjects (≤18 years of age)
- E—human papillomavirus (HPV) infection
- C—none or subjects with and without an HPV vaccine and the type
- O—oral lesions.
2.2. Search Strategy
- 1.
- Human papillomavirus OR HPV
- 2.
- Oral lesions OR oral manifestations OR oral signs
- 3.
- Children OR pediatric OR child OR infant OR adolescent OR teenager OR young.
2.3. Study Selection and Eligibility Criteria
2.4. Data Extraction and Collection
- ▪
- First author, year, journal, funding, study quality;
- ▪
- Design and number of studies reported; sample size, gender ratio, mean age, comorbidities of the population investigated; HPV vaccine (if any; targeted HPV genotypes);
- ▪
- Total number or prevalence of pediatric subjects with oral HPV-related lesions diagnosed through a clinical examination confirmed based on histopathologic analysis (except for FEH) with/without PCR confirmation;
- ▪
- Macroscopic and microscopic features of oral lesions categorized as benign and malignant oral lesions [15];
- ▪
- Definitive diagnosis, diagnostic procedures, treatment, and progression of the oral lesions;
- ▪
- HPV genotypes associated with oral lesions.
2.5. Data Synthesis
- ➢
- Estimating the prevalence of HPV-related lesions in pediatric subjects diagnosed via clinical examination and confirmed based on histopathologic analysis;
- ➢
- Categorizing oral HPV-related lesions into benign, potentially malignant, and malignant lesions and ranking them in descending order of occurrence;
- ➢
- Evaluating the frequency of oral lesions categorized as benign, potentially malignant, and malignant in pediatric subjects
- ➢
- Calculating the frequency of HPV genotype detected in oral lesions;
- ➢
- Comparing the frequency and type of oral lesions in subjects with and without HPV vaccination
- ➢
- Evaluating the oral lesions in relation to the HPV vaccine type.
2.6. Quality Assessment
3. Results
3.1. Study Selection
3.2. Studies Reporting Pediatric Cases Diagnosed with Oral Papilloma, Verruca Vulgaris, or Condyloma Acuminata
3.2.1. Oral Papilloma, Verruca Vulgaris, or Condyloma Acuminata: Case Characteristics
3.2.2. Oral Papilloma, Verruca Vulgaris, or Condyloma Acuminata: Macroscopic and Microscopic Features, Extra-Oral Involvement, HPV Genotype
3.2.3. Oral Papilloma, Verruca Vulgaris, or Condyloma Acuminata: Definitive Diagnosis, Diagnostic Procedure(s), Therapy, Progression
3.3. Studies Reporting Pediatric Cases Diagnosed with Focal Epithelial Hyperplasia
3.3.1. Focal Epithelial Hyperplasia: Case Characteristics
3.3.2. Focal Epithelial Hyperplasia: Macroscopic and Microscopic Features, Extra-Oral Involvement, HPV Genotype
3.3.3. Focal Epithelial Hyperplasia: Definitive Diagnosis, Diagnostic Procedure(s), Therapy, Progression
3.4. Studies Reporting Pediatric Cases Diagnosed with Oral Squamous Cell Carcinoma
3.4.1. Oral Squamous Cell Carcinoma: Case Characteristics
3.4.2. Oral Squamous Cell Carcinoma: Macroscopic and Microscopic Features, Extra-Oral Involvement, HPV Genotype
3.4.3. Oral Squamous Cell Carcinoma: Definitive Diagnosis, Diagnostic Procedure(s), Therapy, Progression
3.5. Prevalence of Reported Oral HPV-Related Lesions in Pediatric Subjects
3.6. HPV Genotypes Detected in Oral HPV-Related Lesions in Pediatric Subjects
3.7. Quality Assessment
4. Discussion
4.1. Oral Benign HPV-Related Lesions in Pediatric Subjects: Verruca Vulgaris, Squamous Cell Papilloma, and Condyloma Acuminatum
4.2. Oral Benign HPV-Related Lesions in Pediatric Subjects: Focal Epithelial Hyperplasia
4.3. Oral Malignant HPV-Related Lesions in Pediatric Subjects: Oral Squamous Cell Carcinoma
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Adler-Storthz K., 1986 J Oral Pathol [26] Case series No funding | Participants Sample size (n.4) Mean age (14.75 y.o.; range 12–16 y.o.) Gender ratio (2M/2F) Country: MD Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: MD HPV vaccine: MD Vaccine type: MD | Macroscopic features: MD Number: MD Distribution: MD Location: 2 lower lip, 2 upper lip, 1 commissure Extra-oral involvement: MD Microscopic features: papillary epithelial projections extending above the adjacent mucosal surface; rete ridges at the periphery were elongated and tended to converge centrally; the epithelial papillae showed varying degrees of acanthosis, granular cell hyperplasia, and hyperparakeratosis; large vacuolated cells with dense nuclei were scattered within the stratum spinosum and granular cell layer of papillae HPV genotype detected: 1 N/A, 3 HPV-2 | Diagnosis Verruca (n.4) Diagnostic procedure(s) 4 Biopsy 4 In situ hybridization Therapy MD Progression MD |
Aldhafeeri K., 2020 Cureus [27] Case report No funding | Participants Sample size (n.1) Mean age (18 y.o.) Gender ratio (1F) Country: MD Comorbidities: none Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: 5 months HPV vaccine: MD Vaccine type: MD | Macroscopic features: a fine strand of tissue over 0.5 cm in length Number: single Distribution: unilateral Location: uvula Extra-oral involvement: MD Microscopic features: finger-like papillary projections lined by hyperplastic squamous epithelium around fibrovascular cores; focal surface parakeratosis lined by benign stratified hyperplastic squamous epithelium composed of elongated hyperchromatic nuclei with eosinophilic cytoplasm HPV genotype detected: MD | Diagnosis Papilloma (n.1) Diagnostic procedure(s) Biopsy Therapy Electrocauterization Progression Healed |
Babich S.B., 2003 JADA [28] Case report No funding | Participants Sample size (n.1) Mean age (4 y.o) Gender ratio (1M) Country: MD Comorbidities: none Ongoing treatments: MD HPV exposure: suspected abuse Relatives with similar lesions: father (genital warts) Time to oral lesion onset: 3 months HPV vaccine: MD Vaccine type: MD | Macroscopic features: papular asymptomatic soft-tissue mass, 4 mm in width, blunt projections (cauliflowerlike); predominantly of the same color as the normal oral mucosa, but with a small brown area at the inferior border Number: single Distribution: unilateral Location: upper lip Extra-oral involvement: 2 genital warts with peripheral satellite lesions Microscopic features: MD HPV genotype detected: 1 HPV-6 and 11 | Diagnosis Condyloma acuminata (n.1) Diagnostic procedure(s) Excisional biopsy In situ hybridization Therapy MD Progression MD |
Beaudenon S., 1987 J Invest Dermatol [29] Case series No funding | Participants Sample size (n.2) Mean age (15.5 y.o.; range 14–17 y.o.) Gender ratio (2M) Country: 2 Caucasians from Denmark Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: MD HPV vaccine: MD Vaccine type: MD | Macroscopic features: MD Number: MD Distribution: MD Location: 1 gingiva; 1 palatoglossal arch Extra-oral involvement: 1 common wart on hand; 1 none Microscopic features: MD HPV genotype detected: 1 N\A; 1 HPV-6 | Diagnosis Condyloma acuminata (n.2) Diagnostic procedure(s) 2 Biopsy 2 In situ hybridization Therapy MD Progression MD |
Benyo, S. 2021 Clin Case Rep [30] Case report No funding | Participants Sample size (n.1) Mean age (13 y.o.) Gender ratio (1F) Country: MD Comorbidities: none Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: 9 months HPV vaccine: No Vaccine type: None | Macroscopic features: multiple clusters of papilloma with one large, isolated papilloma measuring 2 × 3 cm Number: multiple Distribution: bilateral asymmetrical Location: lower lip, cheeks, commissures Extra-oral involvement: (treated) multiple palmar verrucae 2 years in advance Microscopic features: squamous lesion with papillary architecture; focal koilocytic atypia. HPV genotype detected: 1 HPV-6 and 11 | Diagnosis Papilloma (n.1) Diagnostic procedure(s) Biopsy In situ Hybridization Therapy Excisional biopsy of large, isolated papilloma CO2 laser surgery of smaller papillomas CO2 laser surgery of the recurrent papillomas Progression Recurrence of the smaller papillomas after 6 and 13 months |
Boj, J.R. 2007 Quintessence Int [31] Case report No funding | Participants Sample size (n.1) Mean age (12 y.o.) Gender ratio (1F) Country: MD Comorbidities: none Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: less than 15 months HPV vaccine: MD Vaccine type: MD | Macroscopic features: small soft fragment (0.25 cm in size) of papillomatous appearance with a whitish outer surface Number: single Distribution: unilateral Location: gingiva Extra-oral involvement: MD Microscopic features: tissue covered by keratinizing stratified squamous epithelium with marked hyper- and parakeratosis; superficial epithelial cells with pyknotic nuclei and perinuclear clear spaces, indicative of HPV infection; the underlying chorion showed dilated vascular spaces and chronic inflammatory changes HPV genotype detected: MD | Diagnosis Papilloma (n.1) Diagnostic procedure(s) Biopsy Therapy Laser surgery Progression Healed after 6 months |
Carneiro, T.E. 2009 J Oral Sci [32] Case series No funding | Participants Sample size (n.4) Mean age (8 y.o./range 4–14 y.o.) Gender ratio (2M/2F) Country: MD Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: 28.3 months (range 2–72 months) HPV vaccine: MD Vaccine type: MD | Macroscopic Features: 2 cauliflower, whitish, softened/flaccid, sessile lesions of 0.3 or 0.5 cm; 2 rounded, rosy/pink/whitish, softened/flaccid pedunculated lesions of 0.2 or 0.3 cm Number: 4 single Distribution: 4 unilateral Location: 2 lower lips, 1 tongue, 1 commissure Extra-oral involvement: MD Microscopic features: normal epithelium maturation pattern, hyperparakeratosis, discrete increase in the number of cells in the basal layer (basilar hyperplasia) of the epithelium in at least one segment, koilocyte-like cells HPV genotype detected: MD | Diagnosis Papilloma (n.4) Diagnostic procedure(s) 4 Biopsy Immunohistochemistry for p53 protein Therapy MD Progression MD |
Chaitanya, P. 2018 Int J Clin Pediatr Dent [33] Case report No funding | Participants Sample size (n.1) Mean age (10 y.o) Gender ratio (1F) Country: MD Comorbidities: none Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: 1 month HPV vaccine: MD Vaccine type: MD | Macroscopic features: pale, pink-colored, pedunculated growth with finger-like projections of soft tissue (1.5 cm) Number: single Distribution: unilateral Location: hard palate Extra-oral involvement: none Microscopic features: papillary projections of parakeratinized stratified squamous epithelium of variable thickness with localized areas showing mild basilar hyperplasia with few koilocytes and enclosing connective tissue cores fibrocellular in nature, with moderate vascularity HPV genotype detected: MD | Diagnosis Papilloma (n.1) Diagnostic procedure(s) Biopsy Therapy Excisional biopsy Progression MD |
De Meneses, R.K.L. 2020 Oral Surg Oral Med Oral Pathol Oral Radiol [34] Case report No funding | Participants Sample size (n.1) Mean age (9 y.o.) Gender ratio (1M) Country: MD Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: 18 months HPV vaccine: MD Vaccine type: MD | Macroscopic features: verrucous nodule measuring 1 cm Number: Single Distribution: Unilateral Location: lower lip Extra-oral involvement: None Microscopic Features: hyperplasia of parakeratinized squamous epithelium, with exophytic projections exhibiting acanthosis and exocytosis; clear cytoplasm cells, suggestive of koilocytosis and subjacent fibrovascular connective tissue was also observed HPV genotype detected: MD | Diagnosis Condyloma acuminata (n.1) Diagnostic procedure(s) Biopsy Therapy Excisional biopsy Progression No recurrence after 1 year |
Devi, R.S. 2014 Case Rep Dent [35] Case report No funding | Participants Sample size (n.1) Mean age (10 y.o.) Gender ratio (1M) Country: MD Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: 7 years HPV vaccine: MD Vaccine type: MD | Macroscopic features: small disc-like mass-pedunculated (3 × 2 cm) Number: single Distribution: unilateral Location: uvula Extra-oral involvement: MD Microscopic features: pattern of finger-like projections with a central vascular zone surrounded by stratified squamous epithelium; multiple papillary folds are hyperparakeratotic and epithelium also revealed plenty of koilocytes HPV genotype detected: MD | Diagnosis Papilloma (n.1) Diagnostic procedure(s) Biopsy Therapy Excisional biopsy Progression MD |
Emmanouil, D.E. 1987 Pediatr Dent [36] Case report No funding | Participants Sample size (n.1) Mean age (5 y.o) Gender ratio (1F) Country: MD Comorbidities: impetigo and gonorrhea Ongoing treatments: antibiotics HPV exposure: suspected abuse Relatives with similar lesions: none Time to oral lesion onset: MD HPV vaccine: MD Vaccinetype: MD | Macroscopic features: 2 wart-like lesions (5 mm in diameter) with verrucous appearance and a slightly paler color than normal oral mucosa. Number: multiple Distribution: unilateral Location: lower lip Extra-oral involvement: 2 skin warts Microscopic features: mushroom-shaped soft hemorrhagic tissue; the surface was velvety and verrucous in appearance; the cut surface revealed papillary pinkish-white tissue; sections of squamous epithelium manifested papillary hyperplasia and acanthosis; many of the squamous epithelial cells showed cytoplasmic vacuolization that causes flattening of the nucleus; some of the cells contained irregular hyperchromatic nuclei; the subepithelial connective tissue showed a few mononuclear inflammatory cells; no viral inclusions were identified HPV genotype detected: MD | Diagnosis Condyloma acuminata (n.1) Diagnostic procedure(s) Vaginal coltures: (+) Neisseria lactamina, Neisseria meningitidis, Neisseria gonorrhoeae Therapy Cryosurgery for skin warts Excisional biopsy for oral warts Progression No recurrence after 6 months |
Liu, N. 2013 J Craniofac Surg [19] Case report National Natural Science Foundation of China; Doctoral Program of the Ministry of Education of China | Participants Sample size (n.1) Mean age (12 y.o) Gender ratio (1M) Country: China Comorbidities: none Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: none Time to oral lesion onset: 1 month HPV vaccine: MD Vaccine type: MD | Macroscopic features: pale, slightly protruded, soft, asymptomatic papules of 1–10 mm in diameter; protruded, pink masses with the surface covered by short, blunt, fine finger-like projections resembling a cauliflower configuration Number: multiple Distribution: bilateral Location: upper lip, cheeks, retromolar area, gingiva, tongue Extra-oral involvement: none Microscopic features: exophytic papillary growths, parakeratosis, and severe acanthosis of epithelium with elongated and widened rete ridges; mild epithelial dysplasia was detected; cellular swelling, edema, and perinuclear vacuoles were observed in the upper layers of the epithelium, indicating virus infection HPV genotype detected: HPV-16 | Diagnosis Papilloma (n.1) Diagnostic procedure(s) Biopsy Serological tests: (-) HIV, anti-syphils antibodies PCR analysis Therapy Oral surgery Progression No recurrence after 1 year |
Misir, A.F. 2013 J Indian Soc Pedod Prev Dent [22] Case report No funding | Participants Sample size (n.1) Mean age (5 y.o.) Gender ratio (1F) Country: MD Comorbidities: none Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: 2 months HPV vaccine: MD Vaccine type: MD | Macroscopic features: soft pink-coloured lesion approximately 0.7 cm in length Number: single Distribution: unilateral Location: hard palate Extra-oral involvement: MD Microscopic features: hyperplastic squamous epithelium and multiple finger-like projections with fibrovascular core; dense connective core with benign proliferation of stratified and squamous epithelium without cell atypia HPV genotype detected: MD | Diagnosis Papilloma (n.1) Diagnostic procedure(s) Biopsy Therapy Laser surgery Progression Healed after 1 month No recurrence after 1 year |
Naghashfar, Z. 1985 J Med Virol [23] Case series No funding | Participants Sample size (n.2) Mean age (12 y.o\range 9–15 y.o.) Gender ratio (1M/1F) Country: 1 Black; 1 MD comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: 1 MD; 1 several months HPV vaccine: MD Vaccine type: MD | Macroscopic features: MD Number: MD Distribution: MD Location: 1 gingiva, 1 lip Extra-oral involvement: 1 MD; 1 wart on forehead Microscopic features: 1 multiple papillomatous structures consisting predominantly of parakeratotic stratified squamous epithelium; occasional cells within the superficial zones displayed perinuclear vacuolization, often with nuclear pyknosis HPV genotype detected: 1 N\A; 1 HPV-6 | Diagnosis Papilloma (n.2) Diagnostic procedure(s) 2 Biopsy 2 Immunoperhoxidase tests for viral antigen 2 In situ hybridization Therapy MD Progression MD |
Orenuga, O.O. 2018 Niger J Clin Pract [37] No funding | Participants Sample size (n.1) Mean age (5 y.o) Gender ratio (1F) Country: MD Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: 3 months HPV vaccine: MD Vaccine type: MD | Macroscopic features: warty pedunculated growth of size around 10 × 7 mm, pink in color, firm in consistency Number: single Distribution: unilateral Location: hard palate Extra-oral involvement: none Microscopic features: hyperkeratinized stratified squamous epithelium with thin fibrovascular connective tissue core contained small endothelial lined vascular channels and a few chronic inflammatory cells consisting mostly of lymphocytes; koilocytes cells were also seen HPV genotype detected: MD | Diagnosis Papilloma (n.1) Diagnostic procedure(s) Biopsy Therapy Excisional biopsy Progression Recurrence after 2 years |
Padayachee, A. 1994 J oral Patho Med [38] Case series S.A. Medical Research Council | Participants Sample size (n.6) Mean age (11.7 y.o./range 10–15 y.o.) Gender ratio (1M/5F) Country: MD Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: MD HPV vaccine: MD Vaccine type: MD | Macroscopic features: MD Number: MD Distribution: MD Location: 3 lip, 1 tongue, 1 gingiva, 1 N/D oral mucosa Extra-oral involvement: 2 warts on hands, 4 none Microscopic features: MD HPV genotype detected: 3 HPV-2 and 57; 3 N/A | Diagnosis Verruca Vulgaris (n.6) Diagnostic procedure(s) Biopsy In situ hybridization Therapy MD Progression MD |
Paradisi, M. 1992 Pediatr Dermatol [39] Case report No funding | Participants Sample size (n.1) Mean age (4 y.o.) Gender ratio (1M) Country: Somalia Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: foster relatives with genital condylomata Time to oral lesion onset: 1.5 years HPV vaccine: MD Vaccine type: MD | Macroscopic features: soft and reddish papillary lesions from 1 to 10 mm Number: multiple (approximately 60) Distribution: bilateral asymmetrical Location: cheeks, upper and lower lips, tongue Extra-oral involvement: none Microscopic features: hyperplastic epithelium with acanthosis, parakeratosis, and papillomatosis; epithelial cells with pyknotic nuclei and distinct perinuclear vacuolization (keratinocytes); slight perivascular inflammatory infiltrate and dermal papillae with largely distorted capillaries in the upper dermis; slight thickening of the stratum corneum, focal areas of parakeratosis and acantholysis HPV genotype detected: 1 HPV-6 and 11 | Diagnosis Condyloma acuminata (n.1) Diagnostic procedure(s) Serological tests: normal Biopsy In situ hybridization Therapy First step: interferon alpha-2a (16 doses) Second step: podophyllin (20%) in ethanol + local interferon Third step: local podophyllin Progression Healed after the first and second steps of therapy Several months later: local recurrence of small lesions Healed after third step |
Percinoto, A.C.C. 2014 BMC Res Notes [40] Case report No funding | Participants Sample size (n.1) Mean age (5 y.o.) Gender ratio (1M) Country: Caucasian Comorbidities: MD Ongoing treatments: MD HPV exposure: sexual abuse Relatives with similar lesions: MD Time to oral lesion onset: MD HPV vaccine: MD Vaccine type: MD | Macroscopic features: one lesion approximately 0.4 mm diameter with a pedicle base, and another one, with a sessile base of approximately 0.6 mm in diameter; both lesions had a firm consistency, reddish appearance, and presence of whitish areas and regions of ulceration Number: multiple (2) Distribution: unilateral Location: tongue, hard palate Extra-oral involvement: MD Microscopic features: acanthotic parakeratinized stratified squamous epithelium containing nuclei with a “raisin type” format in the upper spinous layer HPV genotype detected: MD | Diagnosis Condyloma acuminata (n.1) Diagnostic procedure(s) Biopsy Therapy MD Progression MD |
Piña, A.R. 2019 Med Oral Patol Oral Cir Bucal [2] Retrospective study No funding | Participants Sample size (n.4) Mean age (6.5 y.o.\range 2–10 y.o.) Gender ratio (3M/1F) Country: MD Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: MD HPV vaccine: MD Vaccine type: MD | Macroscopic features: 1 nodular lesions with a slightly papillary surface Number: 2 single/2 multiple Distribution: MD Location: 2 vermilion, 1 gingiva, 1 lips Extra-oral involvement: MD Microscopic features: 1 blunt hyperplastic epithelium with papillary rounded projections showing superficial koilocytes HPV genotype detected: 2 N\A; 2 HPV-6 and 11 | Diagnosis Verruca Vulgaris (n.2) Condyloma acuminata (n.2) Diagnostic procedure(s) 4 In situ hybridization Therapy MD Progression MD |
Premoli-de-Percoco, G. 1993 J Oral Pathol Med [41] Case series C.D.C.H.-U.C.V. | Participants Sample size (n.7) Mean age (8.7 y.o.\range 5–16 y.o.) Gender ratio (6M/1F) Country: MD Comorbidities: MD Ongoing treatments: MD HPV exposure: 2 autoinoculation Relatives with similar lesions: MD Time to oral lesion onset: MD HPV vaccine: MD Vaccine type: MD | Macroscopic features: sessile, with a broad base, and the surfaces are tough and papillary with small clefts and pits Number: MD Distribution: MD Location: 3 hard palate, 2 upper lip, 2 commissure Extra-oral involvement: 2 finger warts Microscopic features: papillomatosis, acanthosis, and hyperkeratosis; vertical tiers of hyperkeratosis are seen overlying the subunits of papillomatous elevations and granular cells with heavy, clutched keratohyalin granules found in the valleys between the elevations; the rete ridges are elongated, characterized by their inward bending at the margin of the verruca, and point radially towards the center of the lesion; vacuolated cells, with small and basophilic nuclei surrounded by a clear halo and pale cytoplasm, are found in the upper spinous and granular cell layers in most cases (koilocyte cells) HPV genotype detected: 7 N\A | Diagnosis Verruca Vulgaris (n.7) Diagnostic procedure(s) 7 Biopsy 7 In situ hybridization Therapy MD Progression MD |
Puranen, M. 1996 Am J Obstet Gynecol [42] Prospective study No funding | Participants Sample size (n.8) Mean age (N\A y.o.) Gender ratio (N\A) Country: MD Comorbidities: MD Ongoing treatments: MD HPV exposure: 8 vertical transmissions Relatives with similar lesions: 8 mothers Time to oral lesion onset: MD HPV vaccine: MD Vaccine type: MD | Macroscopic features: 2 hyperplastic plicae; 1 papillary lesion; 4 small papules (1–2 mm); fibroma (3 mm) Number: 4 single\4 multiple Distribution: MD Location: 3 palate, 1 pharyngeal arcus, 4 N\A Extra-oral involvement: MD Microscopic features: MD HPV genotype detected: 1 HPV-16; 7 MD | Diagnosis Papilloma (n.1) N\A (n.7) Diagnostic procedure(s) 8 Cytologic scrapes 1 Biopsy 1 In situ hybridization PCR analysis Therapy 1 Excisional biopsy Progression MD |
Sabeena, S. 2016 Indian J Med Microbiol [43] Case report ICMR | Participants Sample size (n.1) Mean age (4 y.o) Gender ratio (1M) Country: North Kerala Comorbidities: None Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: none Time to oral lesion onset: 2 months HPV vaccine: MD Vaccine type: MD | Macroscopic features: white-colored warty lesion on the mucosal aspect Number: single Distribution: unilateral Location: lower and upper lip Extra-oral involvement: MD Microscopic features: papillomatous tumor with hyperkeratosis, acanthosis, and cells with koilocytic change HPV genotype detected: HPV-32 | Diagnosis Papilloma (n.1) Diagnostic procedure(s) Biopsy PCR analysis Therapy Electrocauterization Progression Lip lesion healed after 1 month and small satellite sparse lesions were noticed |
Sadaksharam, J. 2019 Indian J Med Res [44] Case report No funding | Participants Sample size (n.1) Mean age (6 y.o) Gender ratio (1M) Country: MD Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: MD HPV vaccine: MD Vaccine type: MD | Macroscopic features: pinkish pedunculated growths Number: multiple (3) Distribution: unilateral Location: vestibule, hard palate, tongue Extra-oral involvement: none Microscopic features: multiple exophytic finger-like projections; hyperplastic stratified squamous epithelium with hyperparakeratosis and papillomatosis enclosing connective tissue core HPV genotype detected: MD | Diagnosis Papilloma (n.1) Diagnostic procedure(s) Biopsy Therapy Excisional biopsy Progression No recurrence after 3 months |
Sinclair, K.A. 2005 Pediatrics [25] Retrospective study Funding | Participants Sample size (n.17) Mean age (4.65 y.o.\range 1.5–12.7 y.o.) Gender ratio (7M/10F) Country: 9 white; 6 Black; 2 Latino Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: MD HPV vaccine: MD Vaccine type: MD | Macroscopic features: MD Number: MD Distribution: MD Location: MD Extra-oral involvement: 7 anogenital warts Microscopic features: MD HPV genotype detected: MD | Diagnosis Papilloma (n.17) Diagnostic procedure(s) 12 Biopsy Therapy MD Progression MD |
Squires, J. 1999 Arch Pediatr Adolesc Med [45] Case series No funding | Participants Sample size (n.3) Mean age (6 y.o.\range 3–9 y.o.) Gender ratio (3F) Country: 1 Caucasian, 2 MD Comorbidities. 2 none, 1 acute respiratory illness Ongoing treatments: 1 Acyclovir HPV exposure: 2 sexual abuse Relatives with similar lesions: 1 none; 1 mother; 1 MD Time to oral lesion onset: 1 several months; 1 less than 6 months; 1 4 months HPV vaccine: MD Vaccine type: MD | Macroscopic features: 1 well circumscribed papillomatous lesion; 1 sessile lesion, generalized hyperplasia, pedunculated lesions; 1 papillomatous mass of 1 cm Number: 1 single\2 multiple Distribution: 1 bilateral Location: 2 tongue, 2 cheeks, 1 commissure, 2 hard palate Extra-oral involvement: 3 none Microscopic features: MD HPV genotype detected: MD | Diagnosis Condyloma acuminata (n.3) Diagnostic procedure(s) 3 Serological test: 3 (-) Treponema pallidum, HIV, and hepatitis B 3 Swabs 3 In situ hybridization Therapy 1 First step: 1 laser surgery; Second step: oral cimetidine for 5 months 2 First step: laser surgery; 2 Second step: laser surgery Progression 1 Recurrence after 1 weeks and worsening after 3 months since the first-step therapy and worsening 10 months since the second step therapy; healed after 1 year 1 Recurrence after 3 months since first-step therapy; no recurrence after 4 months since second step therapy 1 Recurrence after 1 month since the first step therapy and after the second step |
Swan, R.H. 1981 Oral Surg Oral Med Oral Pathol [46] Case report No funding | Participants Sample size (n.1) Mean age (18 y.o) Gender ratio (1M) Country: Caucasian Comorbidities: MD Ongoing treatments: podophyllin for genital lesions HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: 3 months and other 2 weeks HPV vaccine: MD Vaccine type: MD | Macroscopic features: pedunculated cauliflower-like growth measuring approximately 1 cm in diameter; four smaller enlarged filiform and fungiform papillae; small, smooth-surfaced, white or pink bumps or nodules that became enlarged rapidly over a period of days to resemble cockscombs Number: multiple (13) Distribution: tendency to coalesce Location: tongue, upper lip Extra-oral involvement: genital lesions Microscopic features: papillomatosis with parakeratosis, hypergranulosis, and marked acanthosis, scattered vacuolated cells in the spinous layer and occasional mitoses in the basal region; in the superficial subepithelial connective tissue, there were numerous dilated blood vessels, and there was a mild infiltrate of lymphocytes and plasma cells HPV genotype detected: MD | Diagnosis Condyloma acuminata (n.1) Diagnostic procedure(s) Biopsy Therapy First step: podophyllin Second step: excisional biopsy Third step: excisional biopsy Fourth step: excisional biopsy Progression No improvement after first-step therapy New lesions appeared Worsening of some lesions Healing of other lesions New lesion appeared No recurrence for 6 months |
Wadhera, R. 2012 EJENTAS [47] Case report | Participants Sample size (n.1) Mean age (7 y.o.) Gender ratio (1M) Country: MD Comorbidities: none Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: 2 months HPV vaccine: MD Vaccine type: MD | Macroscopic features: pink-colored pedunculated mass measuring 3 × 2 cm with numerous finger-like projections; firm in consistency Number: single Distribution: unilateral Location: uvula Extra-oral involvement: MD Microscopic features: performed but N\A HPV genotype detected: MD | Diagnosis Papilloma (n.1) Diagnostic procedure(s) X-ray Direct laryngoscopy Therapy Excisional biopsy Progression No recurrence after 6 months |
Yoshpe, N.S. 1995 J Pediatr Otorhinolaryngol [48] Case series No funding | Participants Sample size (n.2) Mean age (5 y.o.; range 3–10 y.o.) Gender ratio (1M/1F) Country: 2 Caucasian Comorbidities: MD Ongoing treatments: MD HPV exposure: 2 suspected abuse Relatives with similar lesions: MD Time to oral lesion onset: MD HPV vaccine: MD Vaccine type: MD | Macroscopic features: MD Number: 2 single Distribution: 2 unilateral Location: 2 tonsil Extra-oral involvement: isolated laryngeal papilloma Microscopic features: MD HPV genotype detected: 1 HPV-6 and 11 | Diagnosis Papilloma (n.2) Diagnostic procedure(s) 1 In situ hybridization Therapy MD Progression MD |
Akyol A., 2003 Int J of Dermatol [49] Case report No funding | Participants Sample size (n.1) Mean age (17 y.o.) Gender ratio (1M) Country: MD Comorbidities: none Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: 7 years HPV vaccine: MD Vaccine type: MD | Macroscopic features: asymptomatic papillomatous lesions Number: multiple Distribution: tendency to coalesce Location: lower lip, cheeks, gingivae, tongue Extra-oral involvement: MD Microscopic features: irregular hyperplasia of the epidermis, hypergranulosis, numerous vacuolated cells containing viral inclusion bodies in the upper layers, elongated rete ridges, and sparse perivascular lymphocyte infiltration HPV genotype detected: MD | Diagnosis FEH (n.1) Diagnostic procedure(s) Biopsy Therapy First step: levamisole, interferon, acitretin, electocauterization Second step: three sessions of CO2 laser surgery and interferon alpha-2b Third step: fourth session of CO2 laser surgery and interferon alpha-2b Progression No improvement within 3 years of first step Improvement at the end of the second step |
Beaudenon, S. 1987 J Invest Dermatol [29] Case series No funding | Participants Sample size (n.1) Mean age (18 y.o.) Gender ratio (1M) Country: 1 Greenlandic Eskimos; Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: MD HPV vaccine: MD Vaccine type: MD | Macroscopic features: MD Number: MD Distribution: MD Location: 1 lower lip Extra-oral involvement: 1 common wart on the hand Microscopic features: MD HPV genotype detected: 1 HPV-13 | Diagnosis FEH (n.1) Diagnostic procedure(s) Biopsy In situ hybridization Therapy MD Progression MD |
Bennett, L.K. 2009 Pediatr Dermatol [50] Case report No funding | Participants Sample size (n.1) Mean age (9 y.o) Gender ratio (1F) Country: Hispanic Comorbidities: none Ongoing treatments: none HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: 1 year HPV vaccine: MD Vaccine type: MD | Macroscopic features: soft, pink, noninflammatory exophytic, flat-topeed 2 to 6 mm papules Number: multiple Distribution: MD Location: cheeks, gingiva, lip Extra-oral involvement: MD Microscopic Features: acanthotic epithelium, elongation of the rete ridges and occasional perinuclear vacuoles HPV genotype detected: HPV-13 | Diagnosis FEH (n.1) Diagnostic procedure(s) Biopsy In situ hybridization Therapy None Progression MD |
Binder, B. 2007 Pediatric Dermatol [51] Case report No funding | Participants Sample size (n.1) Mean age (3 y.o.) Gender ratio (1M) Country: Africa Comorbidities: none Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: a few months HPV vaccine: MD Vaccine type: MD | Macroscopic features: soft, asymptomatic, round, flat-topped, pale papules Number: multiple Distribution: bilateral asymmetrical Location: upper and lower lips, tongue Extra-oral involvement: none Microscopic features: non-cornified, highly acanthotic epithelium with elongated rete ridges, numerous mitoses, koilocytosis with perinuclear vacuolation, and intracytoplasmic basophilic granules; the underlying connective tissue displayed elongated papillae with dilated capillaries HPV genotype detected: HPV-32 | Diagnosis FEH (n.1) Diagnostic procedure(s) Biopsy Sierological tests: normal, (-) Treponema pallidum and HIV Therapy Topical imiquimod (refused) Progression MD |
Bombeccari, G.P. 2009 JEADV [52] Case report No funding | Participants Sample size (n.1) Mean age (14 y.o.) Gender ratio (1M) Country: Ecuador Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: none Time to oral lesion onset: MD | Macroscopic features: sessile coalescing papules Number: multiple Distribution: bilateral asymmetrical Location: lip, cheeks, tongue Extra-oral involvement: none Microscopic features: exophytic squamous epithelial proliferation with papillomatosis and mild hyperparakeratosis HPV genotype detected: HPV-13 | Diagnosis FEH (n.1) Diagnostic procedure(s) Incisional biopsy PCR analysis Therapy Diode laser Progression No recurrence after 1 year |
Borborema-Santos, C.M. 2006 Braz Dent J [53] Case series No funding | Participants Sample size (n.5) Mean age (N\A y.o./range 3–17 y.o.) Gender ratio (3M/2F) Country: 5 Central Amazonian Indian communities (Brazil) Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: 2 of the 5 patients are siblings Time to oral lesion onset: MD HPV vaccine: MD Vaccine type: MD | Macroscopic features: soft papular whitish to normally mucosal lesions Number: 5 multiple Distribution: MD Location: lower and upper lip, cheeks, tongue Extra-oral involvement: MD Microscopic features: none HPV genotype detected: 5 HPV-13 | Diagnosis FEH (n.5) Diagnostic procedure(s) 5 Cytobrush 5 PCR analysis Therapy MD Progression MD |
Brehm, B.A. 2016 Pediatr Dermatol [54] Case report No funding | Participants Sample size (n.1) Mean age (11 y.o.) Gender ratio (1F) Country: MD Comorbidities: none Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: 4 years HPV vaccine: MD Vaccine type: MD | Macroscopic features: pink verrucous papules of varying sizes Number: multiple Distribution: bilateral Location: upper and lower lip, tongue, cheeks, gingiva, oral floor Extra-oral involvement: none Microscopic features: hyperplastic squamous epithelium with papillomatosis, acanthosis, and parakeratosis; the rete ridges were widened, elongated, and broad; within the stratum spinosum, there were multiple cells with clumping of nuclear chromatin (mitosoid bodies) and cells with perinuclear vacuolization and irregular nuclei (koilocytes). HPV genotype detected: HPV-13 | Diagnosis FEH (n.1) Diagnostic procedure(s) Blood test: normal Serological test: (-) HIV PCR analysis Therapy Laser and plastic surgery Progression Fewer smaller papules |
Cohen, P.R. 1993 Pediatr Dermatol [55] Case report PHS grant DE08061 | Participants Sample size (n.2) Mean age (6.5 y.o.\range 5–8 y.o.) Gender ratio (2F) Country: 2 Mexico Comorbidities: MD Ongoing treatments: MD HPV exposure: 1 suspected abuse Relatives with similar lesions: patients are sisters Time to oral lesion onset: 1 year HPV vaccine: MD Vaccine type: MD | Macroscopic features: papules of 2–4 mm Number: 2 multiple Distribution: 2 bilateral asymmetrical Location: 2 lower lips, 1 tongue Extra-oral involvement: MD Microscopic features: localized hyperplasia of the epithelium; mild parakeratosis overlaid the acanthotic epithelium, which contained occasional vacuolated cells in the upper layers and random cells demonstrating mitosis-like nuclear degeneration; in the middle and deeper layers of the epithelium, there were a few binucleated cells; the rete ridges were irregularly elongated and showed horizontal anastomosis; there were several dilated vessels in the superficial lamina propria and a sparse perivascular, predominantly lymphocytic infiltrate HPV genotype detected: MD | Diagnosis FEH (n.2) Diagnostic procedure(s) 1 Biopsy 1 In situ hybridization Therapy 1 First step: no therapy 1 Second step: topical podophyllin (25%) elixir in benzoin (5.6) 1 Third step: cryotherapy Progression Worsening of lesions in number and size No improvement after second step of therapy Recurrence of lesions after third step therapy Spontaneous improvement during the following month Healed after 1 year No recurrence after 6 months |
Durso, B.C. 2005 J Cant Dent Assoc [56] Case report No funding | Participants Sample size (n.1) Mean age (21 y.o. but with oral lesions from 11 y.o.) Gender ratio (1F) Country: MD Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: 10 years HPV vaccine: MD Vaccine type: MD | Macroscopic features: several sessile normochromic papulonodular lesions Number: multiple Distribution: bilateral asymmetrical Location: cheek, lip, tongue Extra-oral involvement: MD Microscopic Features: “hyperkeratinized stratified epithelium exhibiting hyperplasia, acanthosis, parakeratosis and deep papillomatous projections; some squamous cells exhibited mitotic figures, called mitosoid cells; the underlying connective tissue was well supplied with collagen and well vascularized, with some congested vessels; there is a lack of inflammatory response and koilocytic cells with perinuclear halo” HPV genotype detected: MD | Diagnosis FEH (n.1) Diagnostic procedure(s) Serological tests: normal Therapy None Progression No alterations after 1 year |
Falaki, F. 2009 J Oral Pathol Med [57] Case series No funding | Participants Sample size (n.6) Mean age (12.3 y.o.\range 9–15 y.o.) Gender ratio (1M/5F) Country: 6 Iran Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: mean of 4.2 months (range 1–8 months) HPV vaccine: MD Vaccine type: MD | Macroscopic features: soft non-tender well circumscribed flat and sessile papules with a color of surrounding mucosa Number: 6 multiple Distribution: bilateral asymmetrical and tendency to coalesce Location: 1 lip, 5 MD Extra-oral involvement: MD Microscopic features: epithelial hyperplasia with acanthosis, parakeratosis, koilocytosis, and mitosis figure HPV genotype detected: 1 N\A; 4 HPV-13; 1 HPV-32 | Diagnosis FEH (n.6) Diagnostic procedure(s) Biopsy PCR analysis Therapy None Progression 4 No regression 1 Regression after 5 years 1 Regression after 2 years |
Garlick, J.A. 1989 J Oral Pathol Med [58] Case series No funding | Participants Sample size (n.3) Mean age (11.7 y.o\range 6–16 y.o.) Gender ratio (3F) Country: Libyan Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: patients 1 and 2 were sisters, patient 3 was a cousin Time to oral lesion onset: 2 MD; 6 months HPV vaccine: MD Vaccine type: MD | Macroscopic features: nodular soft, round, and circumscribed lesions of similar color to the adjacent mucosa Number: 3 multiple Distribution: bilateral asymmetrical Location: 3 upper and 3 lower lips, 3 cheeks, 3 commissure, 3 vermillion Extra-oral involvement: 3 skin warts adjacent lips, 1 hands wart Microscopic features: (n.3) “hyperplasia of the epithelium typified by mild hyperkeratosis, acanthosis, and elongation and anastomosis of rete ridges; (n.1) condensation of keratohyalin granules in the spinous layer, yet showed very few mitosoid cells or koilocytes; (n.1) numerous koilocytes and occasional mitosoid cells in the lower stratum spinosum; (n.1) numerous swollen cells with a pale cytoplasm that demonstrated a ballooning type of degeneration, many of these cells showed pyknotic nuclei and a vacuolated cytoplasm, occasional mitosoid cells, and condensation of keratohyaline granules were also seen in the spinous layer” HPV genotype detected: 3 HPV-13 | Diagnosis FEH (n.3) Diagnostic procedure(s) 3 Biopsy Therapy MD Progression MD |
Hall, C. 2010 Oral Surg Oral Med Oral Pathol Oral Radiol Endod [59] Case report No funding | Participants Sample size (n.3) Mean age (8.3 y.o.\range 5–13 y.o.) Gender ratio (1M/2F) Country: 3 Australia Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: three patients were siblings Time to oral lesion onset: MD HPV vaccine: MD Vaccine type: MD | Macroscopic features: exophytic, sessile, smooth-surfaced nodules ranged in size from 1 to 3 mm in diameter, firm on palpation, and covered by normal pink mucosa Number: 3 multiple Distribution: 3 bilateral asymmetrical Location: 3 tongue, 2 lower lip Extra-oral involvement: MD Microscopic features: 1 polypoid lesion consisting of a fibrous core covered by hyperplastic squamous epithelium with occasional dyskeratotic and mitosoid cells HPV genotype detected: MD | Diagnosis FEH (n.3) Diagnostic procedure(s) 1 Incisional biopsy Therapy MD Progression MD |
Hashemipour, M.A. 2010 Arch Iran Med [18] Case report No funding | Participants Sample size (n.1) Mean age (12 y.o.) Gender ratio (1F) Country: MD Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: 8 years HPV Vaccine: MD Vaccine type: MD | Macroscopic features: lesions with a wide range of sizes, from 5 to 10 mm of the same color as mucosa with no inflammatory appearance, the surface was soft with firm consistency and pediculated Number: multiple Distribution: bilateral Location: vestibule, lower lip, cheek Extra-oral involvement: MD Microscopic features: squamous epithelium with prominent acanthosis and broad elongated rete ridges, epithelial dysplasia was not detected, but there were very isolated mitosoid cells HPV genotype detected: MD | Diagnosis FEH (n.1) Diagnostic procedure(s) Serological tests: normal Incisional biopsy PCR analysis Therapy CO2 laser surgery Progression Healed after 2 weeks |
Liu, N. 2012 Int J Oral Maxillofac Surg [60] Case series National Natural Science Foundation of China; Science Funds for Talented Professionals of Sichuan Province in China | Participants Sample size (n.1) Mean age (7 y.o.) Gender ratio (1F) Country: China Comorbidities: none Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: none Time to oral lesion onset: 1 years HPV vaccine: MD Vaccine type: MD | Macroscopic features: slightly protruded, soft papules with the same color as the surrounding mucosa or wither, ranging from 3 to 10 mm in diameter Number: multiple Distribution: bilateral Location: lips, cheeks Extra-oral involvement: none Microscopic features: parakeratosis and severe acanthosis with elongated and widened rete ridges; epithelial dysplasia was not detected; the nuclei of epithelial cells in the stratum spinosum were enlarged and hyperchromatic with very little nuclear degeneration resembling a mitotic figure (mitosoid cell) HPV genotype detected: HPV-13 | Diagnosis FEH (n.1) Diagnostic procedure(s) Serological tests: (-) HIV and antisyphilis antibodies Biopsy PCR analysis Therapy None Progression MD |
Lorduy, C.M. 2018 Gen Dent [21] Prospective study No funding | Participants Sample size (n.10) Mean age (MD/range 0–10 y.o.) Gender ratio (N\A) Country: MD Comorbidities: no allergy Ongoing treatments: none HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: MD HPV vaccine: MD Vaccine type: MD | Macroscopic features: MD Number: MD Distribution: MD Location: MD Extra-oral involvement: MD Microscopic features: MD HPV genotype detected: MD | Diagnosis FEH (n.10) Diagnostic procedure(s) MD Therapy 10 TCA (5–7 applications) Progression 10 No recurrence after 1 years |
Lutzner, M. 1982 Arch Dermatol [61] Case series Institut National de la Santé et de la Recherche Médicale | Participants Sample size (n.2) Mean age (8 y.o.\range 6–19 y.o.) Gender ratio (1M/1F) Country: 1 Algerian, 1 Moroccan Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: two brothers and one sister Time to oral lesion onset: 5 months; 1 year HPV vaccine: MD Vaccine type: MD | Macroscopic features: soft, slightly elevated, oval-to-round papules, 2 to 5 mm in diameter, with a pink or white surface Number: multiple Distribution: bilateral/tendency to coalesce Location: 2 lips, 2 cheeks, 1 gingiva, 1 tongue, 1 hard palates Extra-oral involvement: 2 skin warts; 1 wart on hands Microscopic features: excised lesions from patients 1 and 2 showed acanthosis of a peculiar type exhibiting irregular elongation, lateral anastomoses, and horizontal, interconnecting branching of the rete ridges (so-called bronze-age ax sign); a few cells throughout the mucosa contained nuclei with abnormal dense granules that in some instances, mimicked mitotic figures; this appearance has been called “mitosoid” degeneration; other cells, especially in the outermost layer, were binuclear; some mononuclear and some binuclear cells exhibited a perinuclear clear zone; in lesions from both patients, a small number of papillomavirus-like particles could be seen in some cells of the outer layer of mucosa to be dispersed sparsely throughout the nucleus; a cell exhibiting a mitosoid nucleus was seen, and the dense, nuclear bodies appeared to be composed of condensed chromatin-like material; since this cell possessed a nuclear membrane, it is unlikely that it was in metaphase; some binuclear cells were infected with papillomavirus-like particles in both nuclei HPV genotype detected: MD | Diagnosis FEH (n.2) Diagnostic procedure(s) Biopsy Therapy 2 Shaving and electrocoagulation Progression 1 No recurrence after 1.5 months |
Mansouri, Z. 2015 Iran J Pathol [62] Case report No funding | Participants Sample size (n.1) Mean age (35 y.o. but with oral lesions from 15 y.o.) Gender ratio (1M) Country: Iran Comorbidities: none Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: 25 years HPV vaccine: MD Vaccine type: MD | Macroscopic features: soft, sessile, smooth surface papules and nodules ranged from 2–10 mm in diameter Number: multiple\tendency to coalesce Distribution: bilateral Location: upper and lower lips, cheeks Extra-oral involvement: MD Microscopic features: squamous epithelium with focal parakeratosis, hyperkeratosis, acanthosis, verrucous proliferation, and marked papillomatosis; hyperplasia of basal cells, and isolated perinuclear cellular vacuolization (koilocytosis), cellular binucleation, and nuclear irregularities were other features; there were well isolated mitosoid cells, but not dysplasia HPV genotype detected: MD | Diagnosis FEH (n.1) Diagnostic procedure(s) Biopsy Therapy None Progression MD |
Martins, W.D. 2006 Int J Paediatr Dent [63] Case report No funding | Participants Sample size (n.1) Mean age (14 y.o.) Gender ratio (1F) Country: white Brazialian Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: none Time to oral lesion onset: several years HPV vaccine: MD Vaccine type: MD | Macroscopic features: elevated sessile, smooth-surfaced nodules firm on palpation, covered by healthy normal-appearing mucosa, ranging in size from 1 to 3 mm in diameter Number: multiple (4) Distribution: MD Location: gingiva Extra-oral involvement: MD Microscopic features: epithelial hyperplasia with acanthosis and hydropic degeneration, parakeratosis, some mitosoidal cells; the rete ridges were frequently joined (the so-called “Bronze Age battle-axe” or “clubs” appearance) HPV genotype detected: HPV-13 | Diagnosis FEH (n.1) Diagnostic procedure(s) Biopsy PCR analysis Therapy Excisional biopsy Progression No recurrence after over 1 year |
Moussavi, S. 1986 J Am Dent Assoc [64] Case series No funding | Participants Sample size (n.2) Mean age (9.5 y.o.\range 6–13 y.o.) Gender ratio (2F) Country: 2 Iran Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Parents with similar lesions: MD Time to oral lesion onset: 1 MD; 1 two years HPV vaccine: MD Vaccine type: MD | Macroscopic features: small nodular and papular lesions Number: 2 multiple Distribution: 1 unilateral/1 bilateral Location: 1 upper and 1 lower lip, 1 cheek Extra-oral involvement: MD Microscopic features: acanthosis and papillomatosis of the stratified squamous epithelium with elongation and anastomosing of the rete ridges; vacuolar degeneration of the spinous layer; the surface layer was slightly parakeratotic; a mild chronic inflammatory cell infiltrate was noticed in the underlying lamina propria HPV genotype detected: MD | Diagnosis FEH (n.2) Diagnostic procedure(s) 2 Biopsy Therapy MD Progression 1 Recurrence after 6 months; improvement after 3 months later; 1 healed after 2 months later 1 Improvement after 4 months |
Nallanchakrava, S. 2018 Int J Clin Pediatr Dent [65] Case report No funding | Participants Sample size (n.1) Mean age (5 y.o.) Gender ratio (1M) Country: MD Comorbidities: none Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: 3 months HPV vaccine: MD Vaccine type: MD | Macroscopic features: soft, sessile papules varying 2–10 cm in dimension Number: multiple (3) Distribution: Bilateral asymmetrical Location: lower lip, tongue Extra-oral involvement: none Microscopic features: benign parakeratotic hyperplastic mucosa with marked papillomatosis and acanthosis, and some of the cells showed isolated perinuclear vacuolization and the presence of occasional mitosoid cells; there was no evidence of dysplasia HPV genotype detected: HPV-32 | Diagnosis FEH (n.1) Diagnostic procedure(s) Blood tests: normal Biopsy PCR analysis Therapy Laser surgery Progression Healed after 1 month |
Nartey, N.O. 2002 J Clin Pediatr Dent [66] Case series No funding | Participants Sample size (n.6) Mean age (8.7 y.o.\range 4–12 y.o.) Gender ratio (1M/5F) Country: Ghana Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: none Time to oral lesions onset: MD HPV vaccine: MD Vaccine type: MD | Macroscopic features: papulonodular or papillomatous type of lesions with sessile bases Number: 6 multiple Distribution: MD Location: 5 lips, 5 cheeks, 3 commissure, 2 gingiva, 1 oral floor, 1 tongue Extra-oral involvement: MD Microscopic features: fibroconnective tissue surfaced by parakeratinised stratified squamous epithelium characterized by acanthosis, bulbous rete ridges, and anastomoses of the rete ridges HPV genotype detected: MD | Diagnosis FEH (n.6) Diagnostic procedure(s) Biopsy Therapy None Progression 4 Spontaneous regression after 18 months 2 Spontaneous regression after 3 years |
Ozden, B. 2011 J Maxillofac Oral Surg [67] Case report No funding | Participants Sample size (n.1) Mean age (7 y.o.) Gender ratio (1F) Country: Caucasian Comorbidities: none Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: 6 months HPV vaccine: MD Vaccine type: MD | Macroscopic features: soft, non-ulcerated and not inflamed sessile papules and nodules from 2 to 10 mm Number: multiple Distribution: MD Location: upper lip, cheeks Extra-oral involvement: none Microscopic features: squamous epithelium with focal parakeratosis, hyperkeratosis, acanthosis, verrucous proliferation, and marked papillomatosis, hyperplasia of basal cells, isolated perinuclear cellular vacuolization (koilocytosis), cellular binucleation, and nuclear irregularities; the presence of epithelial dysplasia was not detected; there were well-isolated mitosoid cells HPV genotype detected: HPV-32 | Diagnosis FEH (n.1) Diagnostic procedure(s) Skin test: normal Serological tests: normal Biopsy PCR analysis Therapy None Progression No improvement after 18 months |
Pfister, H. 1983 J Virol [68] Case report Deutsche Forschungsgemeinschaft | Participants Sample size (n.1) Mean age (13 y.o) Gender ratio (1F) Country: Turkey Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: 3 years HPV vaccine: MD Vaccine type: MD | Macroscopic features: plaques Number: multiple Distribution: MD Location: upper and lower lips, commissures, cheeks Extra-oral involvement: skin warts Microscopic features: strong acanthosis with elongated rete ridges, a significant papillomatosis, and a continuous parakeratosis; large vacuolated cells with deeply basophilic nuclei were found focally in both the lower and the upper stratum malpighii HPV genotype detected: HPV-13 | Diagnosis FEH (n.1) Diagnostic procedure(s) In situ hybridization Therapy MD Progression MD |
Piña, A.R. 2019 Med Oral Patol Oral Cir Bucal [2] Retrospective study No funding | Participants Sample size (n.1) Mean age (11 y.o.) Gender ratio (1M) Country: MD Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: MD HPV vaccine: MD Vaccine type: MD | Macroscopic features: MD Number: 1 multiple Distribution: MD Location: 1 lips Extra-oral involvement: MD Microscopic features: MD. HPV genotype detected: 1 HPV-6 and 11 | Diagnosis FEH (n.1) Diagnostic procedure(s) 1 In situ hybridization Therapy MD Progression MD |
Premoli-de-Percoco, G. 1992 Virchows Arch A Pathol Anat Histopathol [24] Case series Concejo Desarrollo Cientifico y Humanistico—Universidad central de Venezuela; Concejo Nacional de Investigaciones Cientificas y Tecnologicas; Fundacion Polar Venezuela | Participants Sample size (n.9) Mean age (10.2 y.o.\range 6–15 y.o.) Gender ratio (3M/6F) Country: 9 Venezuela Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: four patients are relatives; 9 patients Time to oral lesion onset: MD HPV vaccine: MD Vaccine type: MD | Macroscopic features: nodular elevations Number: 9 multiple Distribution: MD Location: 1 upper lip, 1 tongue, 8 MD Extra-oral involvement: MD Microscopic features: epithelial acanthosis, prominent clubbing and anastomosis of epithelial ridges with basal orientation, mild hyperparakeratosis, enlarged ballooning cells with abnormal nuclear chromatin patterns and multinucleated cells, cells immediately beneath the surface often displayed large cytoplasmic vacuolization with deeply basophilic nuclei HPV genotype detected: 4 HPV-13 | Diagnosis FEH (n.9) Diagnostic procedure(s) 9 Biopsy 9 In situ hybridization Therapy MD Progression MD |
Puriene, A. 2011 Stomatologija [69] Case report No funding | Participants Sample size (n.1) Mean age (15 y.o.) Gender ratio (1F) Country: MD Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: 2 years HPV vaccine: MD Vaccine type: MD | Macroscopic features: multiple slightly elevated normochromic papulonodular lesions Number: multiple Distribution: unilateral Location: cheeks, lip Extra-oral involvement: MD Microscopic features: hyperkeratinized epithelium exhibiting hyperplasia and deep papillomatous projections; acanthosis and parakeratosis are consistent findings; some squamous cells exhibited mitotic figures (koilocytic cells) HPV genotype detected: MD | Diagnosis FEH (n.1) Diagnostic procedure(s) Sexually transmitted diseases tests: negative Biopsy Therapy Excision biopsy Progression MD |
Sarraj, A. 2013 Ann Stomatol [70] Case report No funding | Participants Sample size (n.1) Mean age (13 y.o.) Gender ratio (1F) Country: Hispanic Comorbidities: none Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: MD HPV vaccine: MD Vaccine type: MD | Macroscopic features: soft, non-tender, flattened lesions of the same color of the oral mucosa Number: multiple Distribution: bilateral Location: cheeks, lip, vestibule Extra-oral involvement: none Microscopic features: acanthosis and superficial keratinocytes with koilocytic changes HPV genotype detected: MD | Diagnosis FEH (n.1) Diagnostic procedure(s) Biopsy Therapy Quantum Molecular Resonance Scalpel (3 sessions) Progression Healed |
Saunders, N.R. 2010 Pediatr Infect Dis J [71] Case series No funding | Participants Sample size (n.2) Mean age (9.5 y.o.\range 8–11 y.o.) Gender ratio (1M/1F) Country: 2 southern Guyana Comorbidities: 2 none Ongoing treatments: MD HPV exposure: 1 horizontal transmission (common toothbrush); 1 N\A Relatives with similar lesions: 1 mother and sister Time to oral lesion onset: 1 several years HPV vaccine: MD Vaccine type: MD | Macroscopic features: 2 raised, well circumscribed, soft papulonodular lesions with smooth surface; ranged in color from white to normal mucosal color Number: 2 multiple Distribution: 2 unilateral, 2 bilateral, 1 tendency to coalesce Location: 2 cheeks, 2 tongue Extra-oral involvement: MD Microscopic features: MD HPV genotype detected: 2 HPV-13 | Diagnosis FEH (n.2) Diagnostic procedure(s) 2 PCR analysis Therapy MD Progression MD |
Starink, T.M. 1977 Br J Dermatol [72] Case series No funding | Participants Sample size (n.2) Mean age (6.5 y.o.\range 4–9 y.o.) Gender ratio (1M/1F) Country: 2 Netherlands (two Africans) Comorbidities: none Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: patients are siblings Time to oral lesion onset: 2 and 10 months HPV vaccine: MD Vaccine type: MD | Macroscopic features: 1 well-defined, slightly elevated round and ovoid, partly confluent, soft papules varying from 1 to 10 mm in diameter, normal pink or whitish with a flat to slightly verrucous surface; 1 papule measuring no more than 4 mm in diameter Number: 2 multiple Distribution: MD Location: 2 lower and 2 upper lips, 2 commissures, 1 gingiva, 2 cheeks, 2 palate, 1 tongue, 1 oral floor, 1 anterior faucial pillars Extra-oral involvement: MD Microscopic features: acanthosis and papillomatosis with elongated anastomosing rete pegs; surface layer was slightly parakeratotic; in some places nuclear degeneration and swelling of cells were present in the upper part of the stratum Malpighi; deposits of PAS-positive material Direct and indirect immunofluorescence studies: normal Electron microscopy: cells with large intracytoplasmic vacuoles and with only fragments of tonofilaments especially in the upper part of Malpighian layer; some cells show loss of cytoplasm from the center of the cell to varying degrees, intracytoplasmic organelles are scarce; mitochondria are mostly intact; the vacuoles are often located around the nucleus, the nuclear membrane is intact and nucleoli are present; some nuclei show peripheral clumping of chromatin, other nuclei show indentation of their surface, also in cells without distinct degenerative changes; some cells contain intracellular glycogen HPV genotype detected: MD | Diagnosis FEH (n.2) Diagnostic procedure(s) 1 Blood test: normal 1 Biopsy 1 Tissue culture: negative Therapy 1 Vitamin A (0.05%) Progression 1 Healed spontaneously |
Tan, A.K. 1995 Otolaryngol Head Neck Surg [73] Case series No funding | Participants Sample size (n.2) Mean age (4.5 y.o.\range 4–5 y.o.) Gender ratio (2F) Country: 2 Ikalouit Comorbidities: 2 none Ongoing treatments: 2 none HPV exposure: MD Relatives with similar lesions: patients are sisters; father Time to oral lesion onset: 2 two years HPV vaccine: MD Vaccine type: MD | Macroscopic features: sharply defined, round-to-ovoid, smooth papules measuring 2 to 5 mm with color identical to that of the surrounding mucosa Number: 2 multiple Distribution: 2 bilateral Location: 2 tongue, 2 cheek Extra-oral involvement: 2 none Microscopic features: acanthosis and elongation with prominent clubbing and lateral anastomoses of the rete ridges of the oral epithelium, prominent vacuolization of cells in the upper portion of the epithelium and binucleated epithelial cells in the middle layer HPV genotype detected: MD | Diagnosis FEH (n.2) Diagnostic procedure(s) 1 Biopsy Therapy MD Progression MD |
Wallace, J.R. 1976 J Am Dent Assoc [74] Case report No funding | Participants Sample size (n.1) Mean age (16 y.o.) Gender ratio (1F) Country: Black Comorbidities: MD Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: none Time to oral lesion onset: 1 year HPV vaccine: MD Vaccine type: MD | Macroscopic features: soft, raised, sessile, flat papules varying in size from 2 mm to 1 cm or larger Number: multiple Distribution: MD Location: cheeks, retromolar areas, lips Extra-oral involvement: MD Microscopic features: plaque-like elevation of the surface epithelium caused by a pronounced hyperplasia of the epithelium, broad irregular acanthosis, and club-like rete ridges; the epithelium was basophilic with prominent nuclei extending into the midportion; vacuolation was noted in the stratum Malpighi; mitotic activity was brisk in the basal portion HPV genotype detected: MD | Diagnosis FEH (n.1) Diagnostic procedure(s) Biopsy Therapy MD Progression MD |
Yasar S., 2009 Pediatr Dermatol [75] Case series No funding | Participants Sample size (n.3) Mean age (8.3 y.o.; range 5–17 y.o.) Gender ratio (3F) Country: MD Comorbidities: 3 none Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: 1 MD; 2 none Time to oral lesion onset: 1 year, 3 and 6 months HPV vaccine: MD Vaccine type: MD | Macroscopic features: soft papulo-nodules (0.2–0.5 cm) of the same color as the normal oral mucosa with lobulated and verrucous surface; some were aggregated closely to form slightly elevated plaques Number: multiple (approximately 40–20–10) Distribution: 3 bilateral asymmetrical\1 tendency to coalesce Location: 2 hard palate, 1 cheeks, 3 upper and 3 lower lips Extra-oral involvement: MD Microscopic features: MD HPV genotype detected: MD | Diagnosis FEH (n.3) Diagnostic procedure(s) 3 Blood test: normal Urine test: normal 2 Serological tests: normal Therapy Levamisole 2 Imiquimod cream (5%) 3 TCA (80%) 2 Cryosurgery Progression 1 TCA + cryotherapy: no improvement; lesions resolved after imiquimod 1 TCA for 4 sessions: no improvement; lesions resolved after imiquimod 2 Herpes labialis attack during treatment 3 No recurrence after 1 year |
Lee, N.V. 2020 Oral Surg Oral Med Oral Pathol Oral Radiol [18] Case report Dr. Michele Williams Education and Research Fund, BC Cancer Foundation | Participants Sample size (n.1) Mean age (5 y.o.) Gender ratio (1M) Country: Caucasian Comorbidities: none Ongoing treatments: MD HPV exposure: suspected autoinoculation Relatives with similar lesions: two siblings Time to oral lesion onset: MD HPV vaccine: MD Vaccine type: MD | Macroscopic features: sudden onset swelling; swelling with some whitish exudate Number: single Distribution: unilateral Location: maxillary alveolar ridge Extra-oral involvement: warts on hands, chin, philtrum, and commissures Microscopic features: sheets of proliferative squamous epithelium and occasional keratin formation, with bland cytology and absence of atypia or cellular pleomorphism; anastomosing channels lined by squamous epithelium with hyperkeratosis and microcystic structures resembling “rabbit burrows” and areas with prominent nuclear pleomorphism, hyperchromasia, and numerous atypical mitotic figures, as well as diffuse p16 positivity HPV genotype detected: N\A but positivity for p16 | Diagnosis OSCC (n.1) Diagnostic procedure(s) Periapical radiograph: radiolucency apical to #E and a mesiodens between the 2 permanent central incisors CBCT: palatal soft tissues swelling and impacted mesiodens Biopsy PCR analysis Therapy First step: antibiotics Second step: extraction of #D and #E Third step: biopsy Fourth step: excisional biopsy Fifth step: marginal resection of the anterior emi-maxilla with removal of #8, #7, #6 and #C Progression No response after the first step of therapy Worsening after the second step Recurrence after the third step Healed after 4 weeks since the fifth step |
Magalhaes, M.A. 2016 Oral Surg Oral Med Oral Pathol Oral Radiol [1] Case report No funding | Participants Sample size (n.1) Mean age (8 y.o.) Gender ratio (1M) Country: MD Comorbidities: none Ongoing treatments: MD HPV exposure: MD Relatives with similar lesions: MD Time to oral lesion onset: MD HPV vaccine: MD Vaccine type: MD | Macroscopic features: pink-red, oval soft-tissue mass, measuring 4 cm in maximum diameter Number: single Distribution: unilateral Location: maxillary alveolar ridge Extra-oral involvement: MD Microscopic features: “ulcerated mucosal surface; most of the tumor consisted of sheets of basaloid cells with focal areas of abrupt squamous differentiation and some of the tumor islands had a ragged periphery, with small cords and single tumor cells invading the connective tissue stroma; the basaloid cells had oval, vesicular nuclei without marked pleomorphism and numerous mitotic figures; the surface mucosa showed a focal area of dysplasia; nests of basaloid epithelium with focal squamous differentiation and focal atypia” HPV genotype detected: N\A but positivity for p16 | Diagnosis OSCC (n.1) in T3N0M0 stage Diagnostic procedure(s) Biopsy CBTC: osteolytic lesion with destruction of the buccal cortex; the floor of maxillary sinus was displaced superiorly and there was a thin smooth layer of periosteal new bone over the tumor mass; the roots of the first molar were medially displaced, but there was no evidence of root resorption Incisional biopsy CT: tumor mass displacing the facial artery and the buccal fat plane laterally; the bony crypts of the developing second premolar and the second molar were mostly intact, except for defects adjacent to the lesion, and the follicular spaces of these teeth appeared uniform MRI: no evidence of disease in the regional lymph nodes In situ hybridization for HBV: negative Therapy Partial maxillectomy Progression Healed after 24 months |
Study | Confounding | Selection of Participants | Classification of Interventions | Deviations from Intended Interventions | Bias Due to Missing Data | Measurement of Outcomes | Selection of Reported Result |
---|---|---|---|---|---|---|---|
Adler-Storthz et al., 1985 [26] | Y | Y | Y | Y | Y | PY | Y |
Akyol et al., 2003 [49] | Y | Y | Y | PY | Y | PN | Y |
Aldhafeeri et al., 2020 [27] | Y | Y | Y | Y | PY | Y | Y |
Babich et al., 2003 [28] | Y | Y | Y | Y | Y | Y | Y |
Beaudenon et al., 1987 [29] | Y | Y | Y | Y | Y | Y | Y |
Bennett et al., 2009 [50] | Y | Y | Y | Y | PY | Y | Y |
Benyo et al., 2021 [30] | Y | Y | Y | Y | PY | PN | Y |
Binder et al., 2007 [51] | Y | Y | Y | Y | Y | Y | Y |
Boj et al., 2007 [31] | Y | Y | Y | Y | Y | PN | Y |
Bombeccari et al., 2009 [52] | Y | Y | Y | Y | Y | Y | Y |
Borborema-Santos et al., 2006 [53] | Y | Y | Y | Y | Y | Y | Y |
Brehm et al., 2016 [54] | Y | Y | Y | Y | PY | Y | Y |
Carneiro et al., 2009 [32] | Y | Y | Y | Y | Y | Y | Y |
Chaitanya et al., 2018 [33] | Y | Y | Y | Y | Y | Y | Y |
Cohen et al., 1993 [55] | Y | Y | Y | Y | Y | Y | PY |
De Meneses et al., 2020 [34] | Y | Y | Y | Y | Y | Y | Y |
Devi et al., 2014 [35] | Y | Y | Y | Y | Y | Y | Y |
Durso et al., 2005 [56] | Y | Y | Y | Y | Y | Y | Y |
Emmanouil et al., 1987 [36] | PY | PY | PY | Y | PY | PN | Y |
Falaki et al., 2009 [57] | Y | Y | Y | PY | PY | Y | Y |
Garlick et al., 1989 [58] | Y | Y | Y | Y | Y | Y | Y |
Hall et al., 2010 [59] | Y | Y | Y | Y | Y | PY | Y |
Hashemipour et al., 2010 [18] | Y | Y | Y | Y | Y | Y | Y |
Lee et al., 2020 [20] | PY | Y | PN | PY | PN | N | Y |
Liu et al., 2012 [60] | Y | Y | Y | Y | Y | Y | Y |
Liu et al., 2013 [19] | Y | Y | Y | Y | Y | Y | Y |
Lorduy et al., 2018 [21] | PY | PY | Y | Y | Y | Y | Y |
Lutzner et al., 1982 [61] | Y | Y | Y | Y | PY | Y | Y |
Magalhaes et al., 2016 [1] | PY | PY | Y | Y | Y | PN | Y |
Mansouri et al., 2015 [62] | Y | Y | Y | Y | Y | Y | Y |
Martins et al., 2006 [63] | Y | Y | Y | Y | Y | Y | Y |
Misir et al., 2013 [22] | Y | Y | Y | Y | Y | Y | PY |
Moussavi et al., 1986 [64] | Y | Y | Y | Y | Y | Y | Y |
Naghashfar et al., 1985 [23] | Y | PN | Y | PY | Y | Y | Y |
Nallanchakrava et al., 2018 [65] | Y | Y | Y | Y | Y | Y | Y |
Nartey et al., 2002 [66] | Y | Y | Y | Y | Y | Y | Y |
Orenuga et al., 2018 [37] | Y | Y | Y | Y | Y | Y | Y |
Ozden et al., 2011 [67] | Y | Y | Y | PY | PY | Y | Y |
Padayachee et al., 1994 [38] | Y | PY | Y | Y | Y | Y | Y |
Paradisi et al., 1992 [39] | Y | Y | Y | PY | Y | Y | PY |
Percinoto et al., 2014 [40] | Y | Y | Y | Y | Y | Y | Y |
Pfister et al., 1983 [68] | Y | Y | Y | Y | Y | Y | Y |
Pina et al., 2019 [2] | Y | Y | Y | Y | Y | Y | Y |
Premoli-de-Percoco et al., 1993 [41] | Y | Y | Y | Y | Y | Y | Y |
Premoli-de-Percoco et al., 1992 [24] | Y | Y | Y | PY | Y | Y | Y |
Puranen et al., 1996 [42] | PY | PY | Y | PY | Y | Y | Y |
Puriene et al., 2011 [69] | Y | Y | Y | Y | Y | Y | Y |
Sabeena et al., 2016 [43] | Y | Y | Y | Y | Y | Y | Y |
Sadaksharam et al., 2019 [44] | Y | Y | Y | Y | Y | Y | Y |
Sarraj et al., 2013 [70] | Y | Y | Y | Y | Y | Y | Y |
Saunders et al., 2010 [71] | Y | Y | Y | Y | Y | Y | Y |
Sinclair et al., 2005 [25] | Y | PN | Y | Y | Y | Y | Y |
Squires et al., 1999 [45] | Y | Y | PY | PY | Y | Y | PY |
Starink et al., 1977 [72] | Y | Y | Y | Y | PN | Y | Y |
Swan et al., 1981 [46] | Y | Y | PY | Y | PN | Y | Y |
Tan et al., 1995 [73] | Y | Y | Y | Y | Y | Y | Y |
Wadhera et al., 2012 [47] | Y | Y | Y | Y | Y | Y | Y |
Wallace et al., 1976 [74] | Y | Y | Y | Y | Y | Y | Y |
Yasar et al., 2009 [75] | Y | Y | Y | PY | Y | PY | PY |
Yospe et al., 1995 [48] | Y | Y | Y | Y | Y | Y | Y |
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© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Di Spirito, F.; Pantaleo, G.; Di Palo, M.P.; Amato, A.; Raimondo, A.; Amato, M. Oral Human Papillomavirus Benign Lesions and HPV-Related Cancer in Healthy Children: A Systematic Review. Cancers 2023, 15, 1096. https://doi.org/10.3390/cancers15041096
Di Spirito F, Pantaleo G, Di Palo MP, Amato A, Raimondo A, Amato M. Oral Human Papillomavirus Benign Lesions and HPV-Related Cancer in Healthy Children: A Systematic Review. Cancers. 2023; 15(4):1096. https://doi.org/10.3390/cancers15041096
Chicago/Turabian StyleDi Spirito, Federica, Giuseppe Pantaleo, Maria Pia Di Palo, Alessandra Amato, Annunziata Raimondo, and Massimo Amato. 2023. "Oral Human Papillomavirus Benign Lesions and HPV-Related Cancer in Healthy Children: A Systematic Review" Cancers 15, no. 4: 1096. https://doi.org/10.3390/cancers15041096