Introduction: HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas are two distinct cancers, with HPV-positivity conferring a better prognosis. Smoking status is a complicating factor. There have been scattered literatures on incomplete information regarding the profiles of their patient population. Details including age and gender distributions, TNM staging, histology grading, recurrence time and types, and death rates have been reported incompletely. We explored all the the important clinical profiles of HPV-negative OPSCC, HPV-positive OPSCC in smokers and nonsmokers at our university medical centers.
Objective: To compare detailed clinical profiles of HPV-negative OPSCC and HPV-positive OPSCC in both smokers and nonsmokers. They include patients’ age and gender distribution, comorbidities, histology grading, TNM staging, perineural invasion(PNI) and lymphovascular invasion(LVI), extracapsular extension(ECE), recurrence rate and types, and death rates. We divided HPV-positive OPSCC into smokers and nonsmokers, and compared the different clinical profiles between them to give a better idea of the complicating role of smoking in the development of OPSCC.
Methods: All OPSCC patients at USC tertiary care hospitals from June 2009-July 2015 were retrospectively reviewed. The primary outcome measure was post-treatment two-year follow-up status (locoregional recurrence, distant recurrence, death rate). Other measures included HPV status, smoking history, age, gender, comorbidities, tumor size, nodal and distant metastases, LVI, PNI, ECE, and tumor grade.
Results: 202 OPSCC patients were identified and categorized into three groups: HPV-negative OPSCC group (HPV-), HPV-positive smoker group (HPV+SMK+), and HPV-positive nonsmoker group (HPV+SMK-). HPV- patients are older (61.1±11.6yo) than the other groups. The HPV- group has the highest percentage of females (22.7%), with more comorbidities than the other groups. Grade 2 is the most common grade for HPV- patients, whereas grade 3 is the most common grade for other groups. PNI and LVI are positive at ~40% for all groups, but ECM is very common for HPV- OPSCC(86.7%), which is significantly higher than other groups. There was no difference of bilateral neck metastases. Although HPV+SMK- and HPV+SMK+ patients have relatively lower T stages and higher N stages, there is no significant difference. HPV+SMK- group has the highest TNM stages. All death rates and recurrence rates increase with time, the death rate of HPV- group is 4 times higher than the HPV+SMK+ group and 6 times higher than the HPV+SMK+ group. The major recurrence type of HPV- OPSCC and HPV+SMK+ is locoregional, but it's distant metastasis for the HPV+SMK+ group.
Conclusions: Although HPV-negative OPSCC presents at an earlier stage, compared to HPV+ OPSCC, its prognosis is worse. HPV-positive OPSCC cells are more mobile, metastasizing sooner and further. HPV-negative OPSCC cells are more infiltrative, leading to more locoregional recurrence. HPV-positive patients are younger and healthier at diagnosis, with tendency to be histologically higher grades. Metastatic and recurrent patterns are different between HPV-positive and HPV-negative patients. The death rate of HPV-negative patients is higher, mainly due to locoregional recurrences. Smoking is a significant complicating factor for HPV-positive OPSCC, by making the death rate, recurrence rate, histology grade, and TNM staging shift towards HPV-negative OPSCC. The complicating role of smoking deserves more research.