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= 0.005), with better overall survival (P = 0.007) and disease- clinical outcomes regardless of p16 or HPV positivity. They
free survival (P = 0.008). They conclude that chemotherapy also indicated that p16 does not predicted response to
followed by chemo-radiation therapy is an effective treatment cetuximab.
especially in patients with HPV + OPSCC.
Unlike cervical cancer, regarding OSCC there is not much
In 2010, Ang et al. conducted a retrospective study of the literature on the use of HPV vaccines to treat these tumours.
[38]
association between tumor HPV status and survival among The effectiveness of the HPV vaccine against OSCC is not yet
743 patients with stage III or IV OPSCC who were enrolled proven.
in a randomized trial comparing treatment with accelerated-
fractionation RT+ cisplatin vs. standard-fractionation RT+ In conclusion, there is much controversy about the
cisplatin. Among 323 OPSCC, 63.8% were HPV+, which carcinogenic potential of HPV. Its mechanism usually
presented better 3-year rates of overall survival (82.4% vs. involves the pE7 and pE6 proteins, which can delete p53,
57.1% among patients with HPV- negative tumours; P < 0.001 p21 and pRb routes.
by the log-rank test) and they also had a 58% reduction in the
risk of death (HR, 0.42; 95% CI, 0.27 to 0.66). They concluded HPV+ patients are usually diagnosed at a younger age, mainly
that among patients with OPSCC, tumor HPV status is a strong those with oropharyngeal tumours, presenting positivity first
and independent prognostic factor for survival. of all for HPV16 > HPV18, although it varies depending on the
population and the test used to detect the infection.
Some authors have studied the prognostic influence of some
biomarkers related to HPV infection in OSCC. One of the For more diagnostic performance, the most advisable is to use
most studied biomarkers is p16, being observed that p16+ the combination of several techniques. P16 positivity needs
and HPV+ patients have a better overall survival compared to be mentioned in special attention as a predictor of HPV
with HPV- or HPV+ but p16-. This was corroborated in the infection in the OPSCC for their prognostic and therapeutic
[93]
prospective phase III study of concomitant chemotherapy considerations.
published in 2011 by Rischin et al. In a sample of 465 patients
[37]
with OPSCC stage III or IV, 172 were analysed with evaluable HPV can appear in normal mucosa, benign and precancerous
HPV and p 16INK4A status, and 185 with eligible p16 status. They lesions.
randomized RT+ cisplatin with or without tirapazamine,
concomitantly. They found that p16+ tumours compared to The most commonly accepted is that the presence of HPV
p16- presented: (1) higher rates of overall survival at 2 years divides OSCC, mainly oropharyngeal, in two types of tumours
(91% vs. 74%; HR, 0.36; 95% CI, 0.17-0.74; P = 0.004); (2) higher with different prognostic and therapeutic implications.
rates of relapse-free survival (87% vs. 72%; HR, 0.39; 95% CI,
0.20-0.74; P = 0.003); and (3) lower loco-regional recurrence Despite the great controversy in prognosis, most studies tend
and death rates from other causes. They also observed a trend to indicate that HPV+ OSCC have an increased survival, better
in favour of tirapazamine group in terms of improved loco- treatment response rates, lower risk of death and lower risk
regional control disease in p16- patients (HR, 0.33; 95% CI, of recurrence [Figure 3].
0.09-1.24; P = 0.13). They concluded that OPSCC HPV+ have
a favourable prognosis when treated with cisplatin-based The oropharyngeal region should be analysed separately.
chemotherapy, compared to HPV-. OPSCC HPV+ tend to respond better to radio-chemotherapy
treatments, considering the HPV positivity as a strong and
In 2014, Lassen et al. published a retrospective study independent survival prognostic factor. In addition, if p16+,
[39]
among 1,294 Danish patients with advanced stage OPSCC. these tumours tend to have better survival and loco-regional
They observed that p16 positivity was significantly higher disease-control.
in oropharyngeal than non-oropharyngeal SCC (P < 0.0001).
OPSCC p16+ presented a statistically significant improvement Future research should evaluate the possibility of new
in loco-regional disease control with primary RT [HR (95% treatments.
CI), 0.38 (0.29-0.49)], free survival events [HR (95% CI), 0.44 Financial support and sponsorship
(0.35-0.56)] and overall survival [HR (95% CI), 0.38 (0.29-0.49)],
unlike in non-OP. Nil.

Future therapeutic lines Conflicts of interest
HPV+ OSCC response to RT, chemotherapy and the There are no conflicts of interest.
combination of both are topics widely approached in
the literature and specialized forums. However, little or REFERENCES
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138 Plast Aesthet Res || Volume 3 || May 25, 2016