Commentary: This information is highly important.
Often patients will arrive with an outside biopsy. The biopsy should be processed for p16 testing and a reflex HPV test if p16+. There are no other molecular markers that are indicated for routine testing yet.

 

HPV-related cancers have some distinct characteristics such as they are caused by high-risk HPV (HPV16), restricted to oropharynx, have distinct molecular markers, usually have "good" prognosis, and patients are typically younger and in general good health (Goon et al, 2009).¹ Tumor HPV testing is now "recommended" by NCCN in 2012,² which changed from being "suggested" in 2011. NCCN recommends either immunohistochemistry for analysis of p16 expression or HPV in situ hybridization (ISH) for HPV DNA detection in tumor cell nuclei. The prognosis of HPV status is defined by RTOG 0129 study that compared accelerated concomitant boost radiotherapy to standard radiotherapy. Of the 323 oropharyngeal tumors that were tested 64% were HPV+ and of those, 96% were HPV16+. P16 is a marker of Rb inactivation (Gillison et al, 2009).³ Another study that assessed HPV positivity was TAX324 study where demographics by HPV status showed that from the 110 patients tested, 50% were HPV+, were younger, higher lymph node burden, smaller primary tumors, and better performance status (Posner et al, 2011).⁴ The survival was significantly different for HPV+ compared to HPV- patients. The HPV+ patients also demonstrated better local regional control (Posner et al, 2011).⁴

 

A recent study is consistent with the detection of HPV16 status using a combination of tests such as in Ned's example where IHC and PCR were used. This study evaluated the importance of accurate testing of HPV16. While the tests were comparable in sensitivity, there were significant disparities in specificity when p16IHC, HR HPV ISH, or DNA qPCR was used independently (Schache et al, 2011).⁵

Marshall R. Posner, MD
Director, Head and Neck Medical Oncology, Division of Hematology/Medical Oncology, Mount Sinai School of Medicine
Professor of Medicine, and Professor of Gene and Cell Medicine, The Tisch Cancer Institute
New York, NY

After the initial workup and additional requests, we asked about the most feasible treatment for Ned: surgery with post-op CRT; CRT only; sequential chemotherapy; or palliative chemotherapy/supportive care.

While surgery could be accomplished initially, it does not address the biology of this disease, which will require post-operative CRT and possesses a high risk of distant metastases. In addition, the functional consequences of the surgery would significantly reduce this patient's quality of life (NCCN, 2012).¹

 

CRT offers a standard of care for this stage of disease, and is associated with improved survival compared to radiotherapy alone (Sharma et al, 2010).² Data from randomized phase III trials supports the use of weekly or bolus cisplatin (Adelstein et al, 2003),³ carboplatin and 5-FU (Denis et al, 2004⁴; Bourhis et al, 2012⁵), or cetuximab (Bonner et al, 2010)⁶ with standard fractionated radiotherapy. IMRT would not offer much in terms of salivary sparing given the extent of disease. Radiation would be delivered over 7 weeks (NCCN, 2012).¹

 

Sequential therapy with TPF followed by CRT also represents a standard of care. Phase III trials have demonstrated that TPF (docetaxel, cisplatin, 5-FU) regimens are well tolerated and improve survival and organ preservation compared to PF (Cisplatin, 5-FU; Van Herpen et al, 2007⁷; Posner et al, 2007⁸). There are no completed trials comparing TPF sequential therapy to CRT (Haddad et al, 2012⁹; Lorch et al, 2012¹⁰). Sequential therapy can reduce tumor volume and improve the functional outcome of subsequent definitive CRT, improve local regional control, reduce the risk of distant metastases, and provide response data to inform later treatment decisions.

 

Palliative/supportive therapy might be considered if the patient is not motivated to undertake an aggressive course of therapy, or has significant psychological barriers to completing and rehabilitating from an aggressive therapeutic course.

 

Statement of Participation
The Postgraduate Institute for Medicine certifies that
Mutombo Kankonde, MD
has participated in the enduring material titled
Ned Visit 1: A 57-year-old Man with Human Papillomavirus (HPV) Negative Oropharynx Cancer
on 07-Jan-13 and is awarded 0.5 AMA PRA Category 1 Credit(s)™.
	The Postgraduate Institute for Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
Postgraduate Institute for Medicine 304 Inverness Way South, Suite 100 Englewood, CO 80112 (303) 799-1930 (303) 858-8848 - Fax	Trace Hutchison, PharmD Director of Medical Education Postgraduate Institute for Medicine

 

 

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