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with other HR HPV types [ 35 ]. HPV16 and HPV18 viral loads have been reported
to be a stronger predictor for the persistence of lesions than the load of other HR
HPV types [ 36 ]. Studies have shown that HPV16 and HPV18 load increased with
the increased lesion grade [ 37 ]. In this regard, viral load per unit amount of genomic
DNA is a potential HPV-related biomarker, which could predict those at risk of
cervical cancer development [ 38 ]. Factors that may influence progression include
coinfection with other sexually transmitted infections such as Chlamydia trachoma-
tis, herpes simplex virus or HIV, tobacco smoking, high parity, and immune sup-
pression [ 25 ].
The prognostic value of HPV genotypes has also been studied in patients withcervical cancer treated with radiotherapy. In one study including 327 patients with
cervical cancer treated with radiotherapy alone or concurrent chemoradiation, of the
22 genotypes detected in 98.8% patients, the most common genotypes were HPV
16, 58, 18, and 33. A significant improvement was reported in the chemoradiother-
apy arm of patients with HPV 18 and HPV 58 positive tumors [ 39 ]. Another study
implies that viral DNA status including intactness of E2 gene was evaluated as a
marker for optimization of radiation treatment [ 40 ].
3.5.2 HPV and Oropharyngeal Cancer
Oral infection with HPV is recognized as an independent cause of oropharyngeal
cancer, although the occurrence of HPV-associated head and neck cancer is lower
than those of the genital tract. Studies have shown that 63% of oropharyngeal can-
cers each year are associated with HPV infection [ 41 ] and 95% of HPV-associated
oropharyngeal cancers are HPV16 related [ 42 ]. HPV-associated oropharyngeal can-
cers typically develop near the base of the tongue and in the tonsils.
A higher incidence of HPV-associated oropharyngeal cancers has been related toan increased number of sexual partners and younger adults. A fourfold higher inci-
dence has been observed in men (48,900 cases) as compared to women (12,600
cases). HPV-positive oropharyngeal cancers are associated with oral sex, age
younger than 60 years, infrequent p53 gene mutation, and a more favorable clinical
outcome, whereas HPV-negative cancers are associated with smoking, excessive
alcohol use, age older than 60 years, frequent p53 gene mutation, and poor progno-
sis [ 43 ].
Studies have shown that as compared to those with environmentally related can-cers, patients with HPV oropharyngeal cancer present with a better performance
status, are healthier, and have a higher likelihood of a complete response to treat-
ment [ 44 , 45 ]. Thus, HPV-associated cancers have a favorable outcome with radio-
therapy, and treatment may be optimized depending on the HPV status so as to
achieve the best possible treatment outcome and circumvent treatment-related tox-
icity and morbidity. Hence, less intensive treatment regimens could be used to
achieve a similar treatment efficacy along with decreased toxicity and an improved
quality of life. Several ongoing clinical trials are currently under investigation to
Y. Li and C. Xu