Received: 26 December 2016 | Accepted: 4 April 2017

DOI: 10.1002/hed.24817

PRACTICE GUIDELINES

AHNS Series – Do you know your guidelines?

Lip cancer

William Dougherty, MD1 | Babak Givi, MD2 | Mark J. Jameson, MD, PhD1 ;
Education Committee of the American Head and Neck Society

1
Department of Otolaryngology - Head and
Neck Surgery, University of Virginia Health
Abstract
System, Charlottesville, Virginia
Background: Lip cancer is one of the most curable primary head and neck malignancies, as the
2
Department of Otolaryngology - Head and
prominent location typically lends to an early diagnosis. The incidence of lip cancer varies by sex,
Neck Surgery, New York University Langone
Medical Center, New York, New York ethnicity, and region, but is estimated to be up to 2.5/100 000 in the United States (squamous cell

Correspondence carcinoma [SCC]).

Mark J Jameson, Division of Head and
Methods: This article will review the current literature and National Comprehensive Cancer
Neck Oncologic and Microvascular Surgery,
Department of Otolaryngology - Head and Network practice guidelines in the treatment of lip cancer.
Neck Surgery, University of Virginia Health
Results: Resection of lip cancer with negative margins remains the mainstay of therapy. Positive
System, PO Box 800713, Charlottesville,
VA 22908-0713. nodal disease should be treated with neck dissection and adjuvant radiotherapy.
Email: [email protected]
Conclusion: Lip cancer remains highly curable when diagnosed at an early stage. A multidisciplinary
approach is crucial to treating patients with advanced-stage lip cancer.

KEYWORDS
guidelines, squamous cell carcinoma, lip neoplasm, head and neck cancer, assessment

1 | INTRODUCTION and creates a perioral sphincter that is crucial in maintaining oral com-
petence. The left and right labial arteries, branches of the facial arteries,
Lip cancer is unique in head and neck oncology because of the lip’s loca- create a circumoral vascular arcade around the lips, traveling between
tion at a transition zone, the mucocutaneous junction, predisposing this the mucosa and orbicularis muscle at the level of the vermillion-
site to malignancy related to both sun damage and risk factors tradition- cutaneous junction. The lip lymphatics generally drain into the subman-
ally associated with oral cancer (tobacco and alcohol). Lip cancer is the dibular and submental lymph nodes; the upper lip lymphatics can drain

most common cancer of the oral cavity, and is most common in white to the preauricular and infraparotid nodes as well.

men (2.5/100 000 in the United States).1 Fortunately, lip cancer is read-
ily diagnosable because of its prominent anatomic location. Lip cancer is
2 | HISTOLOGY AND STAGING
also one of the most curable malignancies of the head and neck, with
disease-specific survival reported as high as 98% for early lesions.2 Lip cancer is typically squamous cell carcinoma (SCC; upward of 90%
The anatomic boundaries of the upper and lower lips are the melo- of lower lip malignancies3), but basal cell carcinoma (BCC) also occurs
labial crease and mental crease, respectively. The upper lip is divided commonly on the upper lip, typically with adjacent spread from the
into 3 skin subunits, 2 lateral and 1 medial, divided by the philtral cutaneous skin of the upper lip into the vermillion. Benign or malignant
ridges. The lower lip contains 1 skin subunit. Each vermillion is a modi- salivary tumors of the lips are uncommon and typically present as a
fied mucosal surface, with very few minor salivary glands relative to submucosal mass. The lips are the second most common anatomic
the labial and buccal oral mucosa. There are 3 layers of the lip in cross- location of minor salivary gland tumors after the hard palate.4 Pleomor-
section: the skin anteriorly, mucosa posteriorly, and the orbicularis oris phic adenomas are the predominant minor salivary gland tumors on the
muscle between the skin and mucosa. The orbicularis oris is innervated lips, in contrast with other anatomic sites in which minor salivary gland
by the buccal and marginal mandibular branches of the facial nerve, tumors are more often malignant.

Head & Neck. 2017;1–5. wileyonlinelibrary.com/journal/hed V

C 2017 Wiley Periodicals, Inc. | 1
2 | DOUGHERTY ET AL.

T A B LE 1 American Joint Committee on Cancer staging system for lip cancer

Stage Description

Primary tumor (T)

TX Primary tumor cannot be assessed
Tis Carcinoma in situ
T1 Tumor 2 cm, DOI 5 mm
T2 Tumor 2 cm, DOI >5 mm and 10 mm
or tumor >2 cm and 4 cm, DOI 10 mm
T3 Tumor >4 cm, any DOI
or any tumor, DOI >10 mm
T4a Tumor invades through cortical bone or involves inferior alveolar nerve, floor of mouth, or
skin of face (e.g., chin, nose)
T4b Tumor invades masticator space, pterygoid plates, or skull base and/or encases internal carotid artery

Regional lymph nodes - clinical (cN)

NX Regional lymph nodes cannot be assessed
N0 No regional lymph nodes metastasis
N1 Metastasis in a single ipsilateral node 3 cm in greatest dimension, ENE(-)
N2a Metastasis in a single ipsilateral node >3 cm but not >6 cm in greatest dimension, ENE(-)
N2b Metastasis in multiple ispiateral nodes, none >6 cm in greatest dimension, ENE(-)
N2c Metastasis in bilateral or contralateral nodes, none >6 cm in greatest dimension, ENE(-)
N3a Metastasis in a node >6 cm in greatest dimension, ENE(-)
N3b Metastasis in any node(s) and clinically overt ENE(1)

Regional lymph nodes - pathological (pN)

NX Regional lymph nodes cannot be assessed
N0 No regional lymph nodes metastasis
N1 Metastasis in a single ipsilateral node 3 cm in greatest dimension, ENE(-)
N2a Metastasis in a single ipsilateral node 3 cm in greatest dimension, ENE(1)
or a single ipsilateral node >3 cm but not >6 cm in greatest dimension, ENE(-)
N2b Metastasis in multiple ispiateral nodes, none >6 cm in greatest dimension, ENE(-)
N2c Metastasis in bilateral or contralateral nodes, none >6 cm in greatest dimension, ENE(-)
N3a Metastasis in a node >6 cm in greatest dimension, ENE(-)
N3b Metastasis in a single ipsilateral node >3 cm in greatest dimension, ENE(1)
or multiple ipsilateral, contralateral or bilateral nodes, any with ENE(1)

Distant metastasis (M)

M0 No distant metastasis
M1 Distant metastasis

Prognostic Stage Groups

Stage Group T classification N classification M classification

I T1 N0 M0
II T2 N0 M0
III T3 N0 M0
T1,2,3 N1 M0
IVA T4a N0,1 M0
T1,2,3,4a N2 M0
IVB Any T N3 M0
T4b Any N M0
IVC Any T Any N M1

DOI 5 depth of invasion (not tumor thickness); ENE 5 extranodal extension

Note: Melanoma and nonepithelial tumors such as those of lymphoid tissue, soft tissue, bone, and cartilage are not included.
This table is used with permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original and primary source for this infor-
mation is the AJCC Cancer Staging Manual, Eighth Edition (2017) published by Springer International Publishing.

Incisional biopsy is indicated for diagnosis of lip tumors. Other lesions nodal staging. It should also be noted that clinical nodal staging is now dis-
that may be suspicious for carcinoma of the lip include actinic cheilitis and tinct from pathological nodal staging due to upstaging for histologic ENE.
keratoacanthoma. As shown in Table 1,5 staging of lip carcinoma is similar
to other oral cavity subsites. The table reflects recent changes made to the
2.1 | What are the guidelines for imaging of lip
clinical and pathological staging in the AJCC Cancer Staging Manual, Eighth
cancers?
Edition (2017). Important changes from the previous staging system
include the incorporation of depth of invasion (DOI) into primary tumor Although there is no formal guideline for imaging of lip malignancies,
staging and the integration of extranodal extension (ENE) into regional imaging should be obtained as indicted for primary tumor evaluation.
DOUGHERTY ET AL. | 3

For early-stage lesions, radiographic evaluation is typically not neces- Although management of early lip cancers can be quite straightfor-
sary. Tumors that are greater than 3 to 4 cm in size, demonstrate ward, many benefit from a collaborative multidisciplinary approach,
fixation to the mandible or extension over the gingiva, or those that particularly more advanced lesions. It is recommended that lip cancers
are associated with a loose tooth or mental hypoesthesia should be be presented and discussed in a multidisciplinary environment to arrive
evaluated with a CT or MRI scan to evaluate the presence of bone at the best treatment and posttreatment care plan. Participation in clin-
invasion. Mental foramen enlargement is a key feature of perineural ical trials is encouraged when appropriate and available.
invasion. Obliteration of the fat in the masticator space, pterygopala-
tine fossa, or along the inferior alveolar canal is also suspicious for 3.2 | What is the recommended treatment approach
tumor spread even if there is no bony erosion.6 Less than 2% of previ- for early-stage lip cancer (T1/T2, N0)?
ously untreated lip cancers have distant metastasis at the time of diag-
3.2.1 | Primary
nosis, therefore, an aggressive metastatic evaluation is not necessary
unless the patient has 3 or more nodal metastasis. 7,8 Surgical resection and appropriate reconstruction is preferred.18 Re-
Nodal disease is the single most important prognostic factor in resection is preferred for positive margins, if feasible. Definitive RT can
9
SCC of the lip. Previous reports cite a rate of cervical metastasis from be used where surgical resection is impractical or unsafe. The appropri-
9–14 ate margin for early-stage SCC is a topic of some debate, however, an
SCC of the lip ranging from 4% to 15%, depending on the stage of
the primary, among other factors. In a review of 617 patients with SCC acceptably low (2.8%) recurrence rate is reported for T1 lesions excised
15 with a 3-mm margin and careful intraoperative frozen section analy-
of the lip, 63 patients had nodal metastasis (including those staged
cN0 before elective neck dissection), which was statistically associated sis.19 For more advanced lesions, up to a 1-cm margin is recommended,
with T3/T4 classification and oral commissure involvement. In the clini- again with intraoperative frozen section analysis.20
cally negative (cN0) necks, only 4% of the T1/T2 lesions had nodal The head and neck surgeon should recognize the advantages of
metastasis, versus 15% and 23% for patients with oral commissure Mohs micrographic surgery in treatment of cutaneous lip cancers,
involvement and T3/T4 primary lesions, respectively. Thus, it is recom- allowing for superior margin analysis and tissue preservation. Mohs sur-
mended that patients with advanced-stage tumors and perhaps those gery should be considered for both BCC >2 cm and SCC of the lip >1
with commissure involvement undergo neck imaging. In the case of cm, and particularly when preoperative biopsy suggests an aggressive
T3/T4 tumors, patients with negative radiographic nodal evaluation variant (such as morpheaform BCC), or the tumor is recurrent.21,22
should be considered for elective treatment of the ipsilateral or bilat-
eral (if the lesion crosses midline) supraomohyoid neck, as described 3.2.2 | Neck
below. Elective neck dissection is not recommended, but sentinel lymph node
biopsy can be considered. In the case of a positive sentinel node, com-
pletion neck dissection should be performed.
3 | TREATMENT
3.3 | Adjuvant therapy
3.1 | What are the general guidelines for treatment of
lip cancers? Adjuvant RT can be used for positive margins if re-resection is not fea-
sible. Adjuvant RT should also be used for adverse pathologic features,
Lip carcinoma is generally amenable to surgical resection and for early-
including perineural or lymphovascular invasion.
stage primary lesions, surgery alone is often curative therapy. T4
lesions typically require combined modality therapy with surgery and
3.4 | What is the recommended treatment approach
radiation, with the addition of chemotherapy in select cases. Adequate
for advanced lip cancer (T3/T4, N0; any T, N1-3)?
surgical resection of a lip carcinoma not only includes control of the
primary tumor with appropriate oncologic margin but also demands 3.4.1 | Primary
adequate reconstruction for restoration of oral competence, as dis- Surgical resection and appropriate reconstruction is preferred. For
cussed below. advanced tumors, composite resection, including the mandible or max-
Surgery is generally recommended as a first-line treatment for lip illa, may be necessary. Alternatively, lip cancers in this category can be
carcinoma; however, primary radiotherapy (RT) for early lesions offers treated with definitive radiation, with or without chemotherapy, with
similar control and comparable functional and aesthetic outcomes, par- subsequent neck dissection for persistent nodal disease, and salvage
ticularly with brachytherapy.16,17 There are clear disadvantages to treat- resection for incomplete response at the primary site.
ing early-stage lesions with radiation, namely, the prolonged treatment
period, potential limitation of future reconstructive options in an irradi- 3.4.2 | Neck
ated field, and the risk of osteoradionecrosis of the mandible. It should Elective supraomohyoid neck dissection should be considered in the
be noted, however, that brachytherapy protocols typically last only 1 clinically negative neck for T3 and T4 lesions. One may perform contra-
week, and can be considered if there is a desire to avoid complications lateral neck dissection for large lesions crossing the midline; however,
of general anesthesia in a patient with severe medical comorbidities. it is often unnecessary if the primary tumor is to be treated with
4 | DOUGHERTY ET AL.

adjuvant RT, as the neck can easily be included in the treatment field. 4.2 | What are the guidelines for surveillance after
Therapeutic neck dissection should be performed if there is clinically treatment of lip cancer?
palpable disease or radiographic evidence of nodal spread.
Posttreatment imaging should be based on the risk of recurrence and
generally performed within the first 6 months after treatment. Patients
3.5 | Adjuvant therapy should follow-up every 3 months for the first year, with longer intervals
for subsequent postoperative years.27
Adjuvant RT should be considered for pT3 or pT4 disease, >1 positive
Sun exposure plays a significant role in the development of lip car-
node, and perineural or lymphovascular invasion.23 Postoperative
cinoma, in contrast with other oral cavity cancers, and thorough skin
chemotherapy is indicated for extracapsular spread or a positive surgical
examination and sun protection/avoidance should be recommended as
margin.
routine.28

3.6 | What is the recommended approach to 5 | CONCLUSIONS

reconstruction after resection of lip cancers?
Carcinoma of the lip is a unique disease among head and neck malig-
Included here is only a concise overview of important reconstructive
nancies. The lip’s location at the junction of the cutaneous face and
considerations of lip defects; more comprehensive discussion is avail-
oral cavity predisposes this site to carcinogenesis related to both sun
able in texts devoted to reconstructive facial surgery. Reconstruction
exposure and tobacco (and to a lesser extent alcohol) use. The progno-
of lip defects is often the most challenging aspect of surgical manage-
sis for early-stage lip cancer is excellent, but advanced disease can be
ment for lip cancers. Although cosmesis may be considered paramount
very aggressive and has poor long-term survival. A multidisciplinary
for small superficial lesions, functional restoration is the primary goal
approach is crucial for treatment of lip cancer, including an oncologic
when reconstructing large, full-thickness defects. Full-thickness defects
surgeon, reconstructive surgeon, and a dermatologist, radiation oncolo-
violate the sphincter of the orbicularis oris and are the most successful
gist, and medical oncologist, when indicated.
reconstructive efforts to restore this sphincter, but it must be balanced
against the risk of microstomia.
If a defect involves one-third or less of the lower lip, wedge resec- R EF ER E N CE S

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