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but also morphological analysis of the piece, including all with no PCR techniques between 80% and 90%. Other authors
[95]
cell layers where the virus may be latently. As a method of with more recent publications detected more frequently
[96]
screening for epidemiological studies, Lawton et al. reported HPV2 and 4. [109]
that mouthwash is the technique of choice, although higher
performance by combining different sampling techniques is Focal epithelial hyperplasia (Heck's disease): they usually
obtained. occur in children and young adults. There is usually genetic
predisposition. [112] HPV13 (20%) and HPV32 (60%) are related
Virus relationship with other oral lesions to those lesions. [113-115]
Since the early 1980s some authors have reported the presence
of HPV not only in cancerous lesions of the oral cavity, but Prognosis and treatment
also in premalignant lesions. [15,97,98] Recently, the presence of There is much controversy about the role that infection by
HPV has been identified as an independent prognostic factor the HPV plays in the prognosis and treatment of patients
for survival in patients with OPSCC. Miller and Johnstone with OSCC. Most of the published studies are retrospective.
[38]
[33]
indicate that HPV (low and high risk serotypes) are 2-3 times But they do generally conclude that the presence of HPV
more detected in precancerous mucosa and almost 5 times divides these tumours in two different entities with different
more detected in carcinoma than in non-neoplastic mucosa: prognostic and therapeutic implications. The most commonly
(1) 22.2% in benign leukoplakia; (2) 26.2% in intraepithelial accepted is that patients with OPSCC HPV+ have a better
neoplasias; and (3) 46.5% in OSCC, with a detection probability prognosis due to increased survival, showing better treatment
of high-risk ones 2.8 times higher than low risk. response rates. [36,38,63,116-118]

Jayaprakash et al. published in 2011 a meta-analysis about The most cited paper in the literature is the one published
[34]
[36]
458 oropharyngeal dysplasias, estimating that the prevalence by Fakhry et al. in 2008. They conducted a prospective
of HPV16/18 is 24.5%. They reported that HPV16/18 were phase 2 study of 96 patients with oral, oropharyngeal and
3 times more common in dysplastic lesions (OR, 3.29; 95% laryngeal SCC. All patients received two cycles of induction
CI, 1.95-5.53%) and invasive cancers (OR, 3.43; 95% CI, 2.07- chemotherapy with paclitaxel and carboplatin followed by
5.69%), when compared to normal biopsies. In addition, concurrent weekly paclitaxel and radiotherapy. They detected
they found these two genotypes are at least 2.5 times more HPV (types 16, 33 and 35) with PCR and ISH in 40% of all
common in men than in women. Within oral leukoplakia, patients. They compared their response to treatment with
proliferative verrucous leukoplakia is believed to have a HPV-: OSCC HPV+ have better respond to chemotherapy (82%
[44]
stronger relationship with HPV mainly 16, with a range of vs. 55%, difference = 27%, 95% CI, 9.3-44.7%; P = 0.01) and
onset between 10% and 85%, [99,100] and higher rate of malignant chemo-radiotherapy (84% vs. 57%, difference = 27%, 95% CI,
transformation. [101] Some authors have also reported a 9.7- 44.3%; P = 0.007).
relationship between lichen planus and HPV, ranging from 0
to 100%, [102] which indicates the existing controversy about Patients with OSCC HPV + have a better overall survival rate
this association. at two years [95% (95% CI, 87-100%) vs. 62% (95% CI, 49-74%),
(difference = 33%, 95% CI, 18.6- 47.4%; P = 0.005, log-rank
Many publications are studying virus connection with benign test)] and a lower risk of disease progression than HPV-
lesions or even in normal mucosa, varying its prevalence [Hazard Ratio (HR), 0.27; 95% CI, 0.10-0.75%].
depending on the technique used, many times no PCR
[35]
techniques are used, which may underestimate measurements. In 2007, Ragin and Taioli performed a meta-analysis of 37
As a summary: studies, which conclude that patients with OSCC HPV+ had
a lower risk of death (HR = 0.85 target; 95% CI, 0.7-1.0) and
Appearance in normal mucosa: varies between 0 and 81%. [78,103] lower risk of recurrence (HR = 0.62% target; 95% CI, 0.5-0.8)
It may appear subclinical or latent, [104] being detected by the than in HPV-. Regarding OPSCC they conclude that HPV+ had
extreme sensitivity of the PCR and may be or not related to a reduced risk of death of 28% (Target HR 0.72; 95% CI, 0.5-
the emergence of a future lesion. 1.0) compared with HPV- with a similar result for disease-free
survival (Meta HR, 0.51; 95% CI, 0.4-0.7).
Squamous papilloma: clinically often indistinguishable from
common warts. HPV genotypes 6 and 11 are most frequently In the same year, Rosenquist et al. conducted a prospective
[32]
associated, detected by ISH. [105] study of cases and controls over 128 Swedish patients with
OPSCC to evaluate the influence of different risk factors for
Condyloma accuminatum: it is a sexually transmitted infection recurrence or appearance of new second primaries in the
and it is usually related to HPV 6 and 11 infection, varying first 3 years after the diagnosis. They found, unlike other
its positivity between 75% and 85% in oral lesions. [106,107] published studies that high-risk HPV+ cases had a higher risk
Furthermore it is also related to the HPV 16. [108,109] It is usually of recurrence/second primary tumour, but lower risk of death
present in HIV+ patients. [110] in intercurrent disease, compared with HPV- ones.
Common wart (verruca vulgaris): oral lesions usually result In 2008, Worden et al. [119] conducted a study about the
from autoinoculation from the fingers. It usually occurs response to treatment of 66 patients with OPSCC. They found
in children. The HPV 2 is described as the most frequently that the presence of HPV was significantly associated with
related, followed by HPV 57, [106,111] detected most of the time response to chemotherapy (P = 0.001), chemo-radiotherapy (P
Plast Aesthet Res || Volume 3 || May 25, 2016 137