Ron J. Karni, MD
Associate Professor & Chief
Lip cancer is the most common malignant lesion of the oral cavity, constituting 25-30% of all oral cavity cancer cases and is the second most common malignancy of the head and neck overall (after cutaneous malignancy). Unlike other sub-sites of the oral cavity, sun exposure is a well established risk factor for development of lip cancer. This helps explain why 90% of lip cancers occur on the lower lip, since it has a higher level of sun exposure compared to the upper lip which is shielded by the nose and is angled slightly downwards. There is also a pronounced geographic variability in incidence which is consistent with sun exposure patterns. In the US, the incidence is 1.8 per 100,000 population, whereas in Australia the incidence reaches as high as 13.5 per 100,000, and in parts of Asia lip cancer is virtually nonexistent. Thirty percent of patients with lip cancer have outdoor occupations. Tobacco use, including dip, alcohol use and immunosuppression are also risk factors. HPV has been associated with lip malignancy, but its role in the pathogenesis of the disease is not as defined as with other sub-sites in the oral cavity and oropharynx. This malignancy is more common in males, patients with fair complexions, and in the 6th decade of life. Most lower lip cancers (90%) are squamous cell type and involve the vermillion, whereas upper lip cancer is usually basal cell type and arise from the lip skin. There is a high incidence of second primary skin malignancies in patients with lip carcinoma due to the common sun exposure risk.
Fortunately, lip cancer remains one of the most curable malignancies in the head and neck. The 10 year cause specific survival can be as high as 98% and recurrence free survival is greater than 90%. This is mainly because the lips are prominently located and allow for early detection of lesions. Tumors that are neglected may portend a worse prognosis and progressively involve the skin of the mentum, alveolar mucosa, mandible, floor of mouth, and tongue, as well as locoregional nodal and distant metastasis.
Early detection is essential for improving patient outcomes in these cases. Patients that present with a persistent nonhealing wound or blister on the lips should have a thorough oral examination to evaluate the lesion as well as all other mucosal sites that may be harboring another malignancy. Examination of early stage lesions often reveals an area of crusting and surrounding induration with either leukoplakia or erythroplakia in the mucosa. More advanced lesions are often very prominent with large bleeding masses and disfigurement. These advanced lesions typically have been present for years prior to the patient presentation. Other essential components of the initial examination include assessment of the mental nerve integrity and neck evaluation for nodal metastases. The paired mental nerves can be evaluated by assessing sensation of the lower lip and chin skin on each side of midline. Even in early stages lip cancers can gain access to the mental nerve and involve the mandible by direct extension, perineural invasion or lymphatic spread into the mental foramen. This, in turn, affects treatment required and prognosis.
Incisional biopsy is the preferred diagnostic method as this will allow the pathologist to determine patterns of invasion as well as the presence of perineural invasion. If the tumor is attached to the mandible, if there is metastatic neck disease, or if perineural invasion is suspected, ancillary imaging studies such as a Panorex, CT scan and/or MRI are indicated. Metastatic workup is not routinely indicated because fewer than 2% of patients have distant metastasis at the time of presentation. Staging of lip cancers is performed by the TNM classification system of the AJCC.
Early stage lesions (stages I and II) can be treated with surgical or radiation therapy with similar 5-year survival rates. Late stage lesions fare poorly with radiation alone. Some drawbacks to radiation therapy, however, include a prolonged treatment course (usually 5 days/week for up to 6 weeks) and the potential for whistle deformity of the lips after wound contracture. Osteoradionecrosis is also a potential complication from primary radiotherapy. Therefore, treatment for lip cancer is primarily surgical with a few goals:
- Extirpation of all tissue involved with cancer including the primary lesion, any involved local structures (i.e., mental nerve), and locoregional lymphatics
- Functional reconstruction of the lip defect which includes mastication, retention of saliva in the mouth, and oral speech competence
- Facial cosmesis and return to daily activities
Surgical extirpation is dependent on the extent of the lesion as well as its location. Procedures can range from shave excision of the vermillion to full thickness excisions of the lip and adjacent skin. MOHS surgery is reserved for early stage lesions that are thin (less than 2.5 mm depth) without lip muscle involvement. Adjunctive procedures such as neck dissection and mandibular resections are performed as dictated by the patients’ tumor status.
The complexity of functional and cosmetic reconstruction of lip defects is significant and requires a skilled reconstructive surgeon well experienced in these types of cases. The reconstructive surgeon must be knowledgeable in all types of reconstructive options as the defect size may be different than anticipated driven by intraoperative pathologic margins. In some cases, participation of a skilled speech pathologist is instrumental in rehabilitating the patient’s speech and swallow function post-operatively.
Overall, cancers of the lip are fairly common malignancies of the head and neck especially in our sunny Southwest climate. Fortunately they are highly treatable with excellent cure rates when identified early. Increased awareness among patients and providers alike can help to further improve survival rates. A dedicated team of head and neck oncologic surgeons and reconstructive surgeons is beneficial to improving oncologic survival and functional and cosmetic outcomes.
Lip Cancer Staging
AJCC Cancer Staging Manual (Sixth Edition 2002)
Primary tumor (T)
- TX: Primary tumor cannot be assessed
- T0: No evidence of primary tumor
- Tis: Carcinoma in situ
- T1: Tumor 2 cm or less in greatest dimension
- T2: Tumor more than 2 cm but not more than 4 cm in greatest dimension
- T3: Tumor more than 4 cm in greatest dimension
- T4: (lip) Tumor invades adjacent structures (e.g., through cortical bone, inferior alveolar nerve, floor of mouth, skin of face) (oral cavity) Tumor invades adjacent structures (e.g., through cortical bone, into deep [extrinsic] muscles of tongue, maxillary sinus, skin. Superficial erosion alone of bone/tooth socket by gingival primary is not sufficient to classify as T4)
Regional lymph nodes (N)
- NX: Regional lymph nodes cannot be assessed
- N0: No regional lymph node metastasis
- N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension
- N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension
- N2a: Metastasis in a single ipsilateral lymph node more than 3 cm but not more than 6 cm in dimension
- N2b: Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension
- N2c: Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension
- N3: Metastasis in a lymph node more than 6 cm in greatest dimension
In clinical evaluation, the actual size of the nodal mass should be measured and allowance should be made for intervening soft tissues. Most masses larger than 3 centimeters in diameter are not single nodes but are confluent nodes or tumors in soft tissues of the neck. There are 3 stages of clinically positive nodes: N1, N2, and N3. The use of subgroups a, b, and c is not required but recommended. Midline nodes are considered homolateral nodes.
Distant metastasis (M)
- MX: Presence of distant metastasis cannot be assessed
- M0: No distant metastasis
- M1: Distant metastasis