Systematic Review of Second Primary Oropharyngeal Cancers in Patients With p16+ Oropharyngeal Cancer

Abstract

Objective To systematically review the literature to determine the prevalence and clinical outcomes of second primary oropharyngeal squamous cell carcinoma (OPSCC). Data Sources Search strategies created with a medical librarian were implemented using multiple databases in October 2019. Review Methods The population of interest included adults age >18 years with a p16+ or human papillomavirus-positive OPSCC. The outcome was a synchronous or metachronous second primary OPSCC. Inclusion and exclusion criteria were designed to capture all study designs. In total, 685 records were identified by the search strategy. Two reviewers independently performed the review, extracted data, and performed a quality assessment. Primary Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. A random-effects model was used for the meta-analysis. Results A total of 2470 patients with 35 second primary OPSCCs from 15 studies were identified. The pooled prevalence of second primary OPSCC was 1.4% (range, 0%-14.3%). In the random-effects model, the prevalence was estimated at 1.3% (95% CI, 0.7%-2.3%; P = .51, I2 = 52%). Of the 30 patients with treatment information, 26 (86.7%) received surgical treatment, while 4 (13.3%) underwent nonsurgical therapy. Of the 29 patients with available survival information, 22 (75.9%) had no evidence of disease at last follow-up, 5 (17.2%) ultimately died of disease, and 2 (6.9%) were alive with disease. Conclusion Overall, the rate of second primary OPSCC in patients with an index p16+ OPSCC is low, and most patients are successfully treated. Insufficient evidence currently exists to recommend routine elective tonsillectomy during surgical treatment of p16+ OPSCC.

The Incidence, Survival, and HPV Impact of Second Primary Cancer following Primary Oropharyngeal Squamous Cell Carcinoma: A 20-Year Retrospective and Population-Based Study

“…According to HPV status and the overall risk of SPC, we found a significantly lower risk of SPC in patients with HPV+ OPSCC index tumours. Other studies also found a lower risk of SPC in patients with p16+ OPSCC [ 22 , 32 ] but did not use double positivity for both HPV DNA and p16, as in this study. Based on the same database, Grønhøj, C. et al [ 34 ] established earlier that HPV+ patients are less likely to have both distant- ( p = 0.02) and loco-regional ( p = 0.001) recurrence following OPSCC.…”

“…Alcohol consumption and tobacco smoking are notable risk factors for developing SPC, especially regarding cancers localized in the upper aerodigestive tract, lungs, and oesophagus [ 21 ]. Studies have shown that p16+ OPSCCs have lower risk of SPC [ 22 ], primarily driven by a decrease in SPCs within the upper aerodigestive tract [ 23 , 24 ].…”

Development of second primary malignancies after transoral surgery in human papilloma virus‐positive oropharyngeal squamous cell carcinoma

“…Additionally, if patients with tonsil primaries are treated with definitive radiation, and perhaps even adjuvant radiation, it is plausible that the base of tongue receives a dose of radiation adequate enough to treat a small subclinical SPM of the tongue base, while the contralateral tonsil does not. Additionally, multiple studies have included only patients with tonsil primaries, 25–27 while others lack specific subsite information on the site of the index tumor 4 …”

Transoral robotic surgery with neck dissection versus nonsurgical treatment in stage I and II human papillomavirus‐negative oropharyngeal cancer

“…This was not associated with improved OS in this cohort. TORS has been shown to be safely and effectively utilized in the recurrent setting as well as in second primary oropharyngeal malignancies 25,32 . Additionally, as a single modality, surgery provides the advantage of a one‐time treatment versus repeated daily treatments over several weeks.…”

“…TORS has been shown to be safely and effectively utilized in the recurrent setting as well as in second primary oropharyngeal malignancies. 25,32 Additionally, as a single modality, surgery provides the advantage of a one-time treatment versus repeated daily treatments over several weeks. The acute toxicity of radiation therapy is well described in the literature, which can lead to interruptions or early discontinuation of treatment.…”