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Abstract Immune checkpoint inhibitors (ICIs) are used to treat many types of cancers. However, the effect of ICIs on second primary tumors is still unclear. Some studied have concluded that ICIs could reduce the incidence of second primary tumors, while others found an increased overall risk of second primary cancer after the introduction of ICIs to the treatment of melanoma. Here, we report the case of a patient with advanced non‐small cell lung cancer (NSCLC) who was treated with ICIs in combination with antiangiogenic drugs, and subsequently developed a second primary tumor in the context of a favorable curative effect of the primary lung cancer. From this case, we know that good efficacy of ICIs for a primary tumor does not mean that a second primary tumor will never develop, which reminds clinicians to consider the possibility of a second primary tumor rather than treating it directly as disease progression.

Abstract Background In patients with squamous cell carcinoma of the cervix (SCCC), a squamous cell carcinoma (SqCC) in the lung represents either a second primary tumor or metastasis. This distinction between second primary tumors and lung metastases in patients with SCCC significantly influences patient prognosis and therapy. Here, we aimed to differentiate second primary tumors from lung metastases in patients with SCCC by exploring the HPV status in SqCCs involving the lung within a large cohort. Methods P16 expression was assessed using immunohistochemistry on tissue microarrays including a total of 415 primary lung SqCCs and 21 lung SqCCs with prior SCCC. Following this, we performed HPV DNA typing and the sensitive RNAscope in situ method to screen all the cases for HPV E6/E7 expression, which is a more reliable indicator of transcriptively active HPV in tumor cells. Results The p16 positive expression rate was 13.7% (57/415) in primary lung SqCCs, but HPV DNA was not detected in any of the 57 primary lung SqCC cases that positively expressed p16. In contrast, HPV DNA was detected in all cases (21/21) with prior SCCC. Consistently, all 21 lung SqCCs with prior SCCC (21/21) showed extensive HPV16 E6/E7 expression. In striking contrast, none of the primary lung SqCCs (0/415) had a detectable RNAscope signal. Conclusions HPV does not seem to play a role in the development of primary lung SqCCs. HPV detection may be helpful in distinguishing second primary tumors from lung metastases in patients with SCCC.

Abstract Introduction Routine follow‐up after curative treatment of patients with oral squamous cell carcinoma (OSCC) is common practice considering the high risk of second primaries and recurrences (ie second events). Current guidelines advocate a follow‐up period of at least 5 years. The recommendations are not evidence‐based and benefits are unclear. This is even more so for follow‐up after a second event. To facilitate the development of an evidence‐ and personalized follow‐up program for OSCC, we investigated the course of time until the second and subsequent events and studied the risk factors related to these events. Materials and methods We retrospectively studied 594 OSCC patients treated with curative intent at the Head and Neck Cancer Unit of the Radboud University Medical Centre from 2000 to 2012. Risk of recurrence was calculated addressing death from intercurrent diseases as competing event. Results The 1‐, 5‐ and 10‐year cumulative risks of a second event were 17% (95% CI:14%;20%), 30% (95% CI:26%;33%), and 37% (95% CI:32%;41%). Almost all locoregional recurrences occurred in the first 2 years after treatment. The incidence of second primary tumors was relatively stable over the years. The time pattern of presentation of third events was similar. Discussion Our findings support a follow‐up time of 2 years after curative treatment for OSCC. Based on the risk of recurrence there is no indication for a different follow‐up protocol after first and second events. After 2 years, follow‐up should be tailored to the individual needs of patients for supportive care, and monitoring of late side‐effects of treatment.

Abstract Radiotherapy for nasopharyngeal carcinoma has been reported to cause second primary oral squamous cell carcinoma (s‐OSCC). The prognosis and pathologic characteristic of s‐OSCC are largely unknown. Bmi1 was associated with the repair of radiation‐induced DNA damage, suggesting its possible involvement in the pathologic process of s‐OSCC. Herein, we compared the prognosis between s‐OSCC and primary OSCC (p‐OSCC) and explored the involvement of Bmi1 in s‐OSCC development. In this retrospective study, s‐OSCC and p‐OSCC patients were matched by propensity scores. Their outcomes were compared by univariate and multivariate analyses. The expression of Bmi1 in s‐OSCC and p‐OSCC was detected by immunohistochemistry (IHC). Radiation‐induced Bmi1 alteration in early‐stage was explored in a rat model and HaCaT cells. After matching, 116 pairs of patients with highly balanced characteristics were included. In univariate analysis, the overall survival (OS), disease‐specific survival (DSS), and local recurrence‐free survival (LRFS) were poorer in s‐OSCC than in p‐OSCC (P

Objective: We noticed that a significant proportion of our patients with head and neck mucoepidermoid carcinoma (HNMEC) had second primary malignancies. To our knowledge, such an association has never been described. The aim of our study is to elucidate the association between second primary malignancies and HNMEC., Study Design: Case series with chart review., Setting: Tertiary referral center., Subjects and Methods: We included all patients with histologically proven HNMEC managed in the Department of Surgery, Queen Mary Hospital, from January 2003 through December 2013. Medical records were retrospectively reviewed and analyzed., Results: Fifty-seven patients with HNMEC were identified. Fourteen (24.6%) had second primary malignancies. The commonest second primary malignancy was nasopharyngeal carcinoma, followed by carcinoma of the thyroid. Second primary malignancies developed before HNMEC in 7 patients, with a mean interval of 196 months. Five patients had second primary malignancies after development of HNMEC, with a mean interval of 65 months. Two patients had synchronous second primary malignancies. Clinical patterns of patients with HNMEC with and without second primary malignancies were compared. Major salivary glands were more frequently affected among patients with second primary malignancies, while minor salivary glands were more frequently affected among those without secondary primary malignancies (P = .032). Development of second primary malignancy was not found to affect the survival., Conclusion: About one-fourth of patients with HNMEC had a second primary malignancy. Major salivary glands were more frequently affected among patients with second primary malignancies. Development of second primary malignancy did not affect survival., (© American Academy of Otolaryngology-Head and Neck Surgery Foundation 2014.)