HPV-associated oropharyngeal carcinomas

Images

 HPV-associated tonsillar squamous cell carcinoma (SCC)

• https://twitter.com/ShackletonMD/status/736658658264645632

Although human papillomavirus (HPV)-related oropharyngeal carcinomas (HPV-OPCs) are generally regarded as "poorly differentiated," they actually maintain a close resemblance to the lymphoepithelium of the tonsillar crypts from which they arise: they are basaloid, exhibit minimal keratinization, and are often permeated by lymphocytes.

In rare cases, the presence of cilia in a primary HPV-OPC (ciliated carcinoma) and their persistence in lymph node metastasis can confound the distinction between a benign and malignant process.

Types

 HPV-associated oropharyngeal squamous cell carcinoma
 HPV-associated oropharyngeal ciliated carcinoma (26457358)
 HPV-associated neuroendocrine carcinoma (22301491)

Prognosis

Human papilloma virus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is associated with a favourable prognosis, although approximately 20-25% of patients ultimately develop recurrent cancer.

Most disease recurrence events appear within 3 years; however, long-term follow-up of reported studies are limited, and the risk of late recurrence is unknown.

Some patients developed distant metastases of HPV-related SCC more than 10 years after initial diagnosis and treatment of HPV-related OPSCC. (25435908)

Late disease recurrence may occur after initial diagnosis of HPV-related OPSCC.

 lymph node metastasis

 distant metastases (DM)

• distant metastases in patients with HPV+ OPSCC occurs significantly later after completion of chemoradiotherapy than in patients with HPV- disease.
• Human papillomavirus-initiated OPSCC also appears to involve a greater number of subsites and metastatic sites infrequently seen in head and neck squamous cell carcinoma. (25742025)
• Although DM rates are similar, the natural course of HPV(+) distant metastases differs from that of HPV(-) patients: it may occur after a longer interval, often with a "disseminating" phenotype, and a small number may have prolonged survival after salvage for distant metastases. (22917550)

 pulmonary metastasis

• In a study, 5/6 HPV(+) with lung oligo-metastasis were still alive with stable disease beyond 2-years after salvage procedures for distant metastais (chemotherapy: 3; surgical resection: 2; radiotherapy: 1). (22917550)

 highly aggressive human papillomavirus-related oropharyngeal cancer (23770280)

• Highly aggressive HPV-OSSC can be defined as cancers which had distant metastases in unusual sites (non-pulmonary) at presentation or within 1-year after initial treatment during their clinical course.
• Patients with advanced HNSCC who have distant metastasis to non-pulmonary sites or multiple sites have worse overall survival (OS) than those with limited pulmonary metastasis.
• In a study with 127 patients, those with lung metastases had a median OS of 26 months, compared to 21 months with liver metastases, 14 months in patients with multiple metastatic locations and 13 months with metastases to the skeletal system (21663634).

Treatment and management

 surgery
 radiotherapy

 cisplatin

• cisplatin or cetuximab combined with radiotherapy each yield superior survival in locally advanced squamous cell head and neck cancer (LA-SCCHN) compared with radiotherapy alone. (25107914)

 cetuximab in HER2+ cases

• cisplatin or cetuximab combined with radiotherapy each yield superior survival in locally advanced squamous cell head and neck cancer (LA-SCCHN) compared with radiotherapy alone. (25107914)

CTCs

 Assessment of CTC in non-OPC should prove useful for identification of patients who benefit from treatment intensification. (25057171)

Open references

 Highly aggressive human papillomavirus-related oropharyngeal cancer: clinical, radiologic, and pathologic characteristics. Kaka AS, Kumar B, Kumar P, Wakely PE Jr, Kirsch CM, Old MO, Ozer E, Agrawal A, Carrau RE, Schuller DE, Siddiqui F, Teknos TN. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013 Sep;116(3):327-35. doi : 10.1016/j.oooo.2013.04.011 PMID: 23770280 (Free)

 Metastasis occurring eleven years after diagnosis of human papilloma virus-related oropharyngeal squamous cell carcinoma. Ley J, Wildes T, El-Mofty S, Adkins D. Ecancermedicalscience. 2014 Nov 13;8:480. doi : 10.3332/ecancer.2014.480. eCollection 2014 PMID: 25435908 (Free)

 Phase II study of cetuximab in combination with cisplatin and radiation in unresectable, locally advanced head and neck squamous cell carcinoma: Eastern cooperative oncology group trial E3303. Egloff AM, Lee JW, Langer CJ, Quon H, Vaezi A, Grandis JR, Seethala RR, Wang L, Shin DM, Argiris A, Yang D, Mehra R, Ridge JA, Patel UA, Burtness BA, Forastiere AA. Clin Cancer Res. 2014 Oct 1;20(19):5041-51. doi : 10.1158/1078-0432.CCR-14-0051 PMID: 25107914 (Free)

 Detection of circulating tumor cells for prediction of recurrence after adjuvant chemoradiation in locally advanced squamous cell carcinoma of the head and neck.
Tinhofer I, Konschak R, Stromberger C, Raguse JD, Dreyer JH, Jöhrens K, Keilholz U, Budach V. Ann Oncol. 2014 Oct;25(10):2042-7. doi : 10.1093/annonc/mdu271 PMID: 25057171 (Free)

References

 Natural course of distant metastases following radiotherapy or chemoradiotherapy in HPV-related oropharyngeal cancer. Huang SH, Perez-Ordonez B, Weinreb I, Hope A, Massey C, Waldron JN, Kim J, Bayley AJ, Cummings B, Cho BC, Ringash J, Dawson LA, Siu LL, Chen E, Irish J, Gullane P, Hui A, Liu FF, Shen X, Xu W, O’Sullivan B. Oral Oncol. 2013 Jan;49(1):79-85. doi : 10.1016/j.oraloncology.2012.07.015 PMID: 22917550

 Natural course of distant metastases following radiotherapy or chemoradiotherapy in HPV-related oropharyngeal cancer. Huang SH, Perez-Ordonez B, Weinreb I, Hope A, Massey C, Waldron JN, Kim J, Bayley AJ, Cummings B, Cho BC, Ringash J, Dawson LA, Siu LL, Chen E, Irish J, Gullane P, Hui A, Liu FF, Shen X, Xu W, O’Sullivan B. Oral Oncol. 2013 Jan;49(1):79-85. doi : 10.1016/j.oraloncology.2012.07.015 PMID: 22917550