LIP Cancer     INTRODUCTION  The oral cavity extends from the skin-vermilion junction of the lips to the junction of the hard and soft palate above, and to the line of circumvallate papilla of the tongue below. Specific sites of tumor origin include the lip, floor of the mouth, oral tongue, lower alveolar ridge and retromolar trigone, upper alveolar ridge and hard palate, and the buccal mucosa

Risk factors for tumors of the oral cavity are similar to those for other sites of head and neck cancers. Lip cancers may have additional risk factors related to sun exposure.

Radiotherapy and surgery are the standard curative treatment modalities for early head and neck cancer (HNC). By definition, patients with stage I and II disease have no evidence of nodal involvement.

The differences in five-year survival rates for stages I through IV disease are illustrated by the following data derived from the Surveillance, Epidemiology and End Results (SEER) database of the National Cancer Institute :

Lip cancer:

  • Stage I     73 percent (cause-specific survival [CSS], 83 percent)
  • Stage II    64 percent (CSS, 73 percent)
  • Stage III   56 percent (CSS, 62 percent)
  • Stage IV  41 percent (CSS, 47 percent)

LIP CANCER  The lip is the most common primary site within the oral cavity, accounting for approximately one-quarter of cancers at this site. The majority of lesions occur on the lower lip and 95 percent occur in males. In a review of 1252 patients, 21 percent of all lip cancers in women arose on the upper lip, compared to only 3 percent in men . Basal cell carcinomas (BCCs) may arise from the skin and cross the vermilion border to invade the lip, while squamous cell cancers (SCCs) most frequently develop at the vermilion margin. BCCs are more common on the upper lip. In the previous series, BCCs comprised 13 percent of upper lip cancers compared to less than 1 percent of lower lip cancers.

Epidemiology  Globally, high incidence rates for lip cancer in men are reported in regions of North America (12.7 per 100,000 per year) and Europe (12.0 per 100,000 per year), while it is virtually unknown in parts of Asia. The reasons for this worldwide variation in incidence are unknown. Factors commonly cited as important in the etiology of lip cancer include solar radiation, tobacco smoking, and viruses such as human papillomavirus (HPV)  Immunosuppression also appears to play a role. One series of 160 recipients of a renal transplant revealed an increased incidence of leukoplakia, dysplasia and squamous cell carcinoma when compared to 160 normal controls.

General principles of treatment  The cure rates of stage I SCC of the lower lip are favorable whether treated by radiotherapy or surgery, and local control rates are similar . Surgery is often preferred over radiation for lip cancer because of potential morbidities from radiation.

Surgery is the treatment of choice for early stage lesions. Defects that involve less than two-thirds of the lip usually can be closed primarily. Defects involving two-thirds of the lip can be reconstructed with full thickness pedicled flaps ("Abbe or Estlander") from the upper or lower lip . Many reconstructive options are available for defects larger than two-thirds of the lip, ranging from local nasolabial flaps to hair-bearing free flaps. The facial artery musculomucosal flap has shown application and success in upper and lower lip reconstruction . This intraoral pedicled flap can provide bulk and "lip-like" texture and color to large lip defects. Radiation therapy is generally reserved for recurrent tumors, nodal disease, and for patients who cannot tolerate surgery.

Prognosis  The prognosis of lip cancer depends upon multiple factors. In a review of 1252 patients, large tumor size and inadequate surgical margins had a negative impact upon survival, as did high tumor grade, cervical adenopathy, and a site of involvement other than the lower lip .

Upper lip cancers and those affecting the oral commissure behave somewhat differently than lower lip cancers . Cancers involving the upper lip and commissure tend to grow more rapidly, ulcerate sooner and metastasize earlier than those of the lower lip . Carcinomas in these sites may metastasize to preauricular nodes as well as submandibular nodes .

Maximum tumor thickness is a predictor of metastatic spread to the regional nodes, and is therefore important for treatment planning and assessment of prognosis in patients with squamous cell carcinoma . In one report of 27 patients with squamous cell carcinoma of the lower lip, 13 had histologically confirmed cervical nodal metastases . There was a significant difference in mean tumor thickness between patients with or without cervical metastases (5.6 versus 3.79 mm, respectively).

The use of a scoring system that includes tumor thickness (the Martinez-Gimeno Scoring System [MGSS]) to predict the likelihood of neck metastases as a means of selecting patients with a clinically negative neck for elective neck dissection, is discused below.

Surgery  Surgical treatment for stage I SCC of the lip has a very favorable outcome. In one study of 184 consecutive patients who were surgically treated, disease control was obtained in 90 percent . Local recurrence and/or regional metastases occurred in 5 percent of patients who were salvaged successfully with surgery or radiation therapy. Local recurrence was associated with large tumors and positive margins. Disease-free survival rates at 5 and 10 years were 86 percent and 81 percent respectively.

  Management of the neck  The incidence of regional metastases ranges from 0 to 15 percent for T1, and 11 to 35 percent for T2 tumors, respectively . Lower lip cancers do not metastasize to lower cervical nodes without invading submental and submandibular lymph nodes. For this reason, elective neck treatment is usually not performed for T1 tumors. For patients with T2 or larger tumors and clinically N0 disease, we also recommend dissection of level Ia through level III nodes on the affected side, with strong consideration for bilateral dissection if the tumor is thicker than 3 mm .

All patients with palpable neck nodes typically undergo a supraomohyoid (level I to III) neck dissection in conjunction with en bloc resection of the primary tumor.

As noted above, a scoring system that includes tumor thickness (the Martinez-Gimeno Scoring System [MGSS]) has been developed to predict the likelihood of neck metastases in patients with oral cavity cancer, including lip cancer. The MGSS was derived from a sample of 126 patients with oral cavity cancer who underwent primary surgery and neck dissection at a single Spanish institution . The derived model was based upon points given for T-stage, tumor thickness, microvascular and perineural invasion, the histologic grade of differentiation, and presence of an inflammatory infiltrate. Patients were then classified into one of four groups on the basis of their MGSS score (total number of points.

The model was applied to a validation cohort of 79 consecutive patients with oral cavity cancer, also treated at the same institution, all of whom had neck dissection . Rates of metastatic neck disease in the four groups in this validation cohort were as follows:

  - Group I (7 to 12 points): 0 percent
  - Group II (13 to 16 points): 21 percent
  - Group III (17 to 20 points: 50 percent
  - Group IV (21 to 30 points): 67 percent

  Mohs micrographic surgery Mohs micrographic surgery (MMS) has been used successfully for lip cancers . In one series of 50 patients, there were no tumor related deaths or metastases with five years of follow-up . Forty-six patients (92 percent) remained free of disease and all patients with recurrent disease were successfully treated with further MMS.

  Postoperative radiation Although there are no published randomized trials, postoperative radiation therapy is indicated following resection for patients with positive margins or pathologically positive lymph nodes.

Radiation therapy  The target volume is the primary tumor with 2 cm margins, clinically determined by visual inspection and bimanual palpation. Treatment is administered using appositional electrons or orthovoltage photons (100 to 250 kVp). An intraoral stent is placed behind the lip to shield the oral cavity and mandible. Interstitial brachytherapy (IB) may be used as primary therapy or as a local boost in conjunction with external beam radiation. Elective neck irradiation is not usually indicated for early lesions (see above).

For T1 lesions (ie, less than 2 cm) we use 50 Gy/25 fractions plus a 16 Gy/8 fraction boost (reducing margins to 1 to 1.5 cm) by EBRT or 65 to 75 Gy over 5 to 7 days by IB. For T2 lesions (ie, 2 to 4 cm), we use 50 Gy/25 fractions plus 16 to 20 Gy/8 to 10 fractions boost by EBRT or 25 Gy IB boost.

With radiation therapy, the expected local control rate depends upon the primary tumor size . In one study of 108 patients with SCC of the lower lip, for example, local control was achieved in 99 percent of T1 lesions and 76 percent of T2 lesions . Local failures at the primary site and in the neck were successfully salvaged by surgery, resulting in a definitive control rate of 98 percent at a median follow-up of 77 months. These results are comparable to, or better than, those achieved with surgery in 184 patients with stage I or II lip cancer treated at the same institution over the same time period .

  Brachytherapy  Excellent results have also been reported with both low-dose rate and high-dose rate IB . In one series of 57 patients with SCC of the lower lip, 47 of whom had stage T1 or T2 disease, actuarial local control with low-dose rate IB was 90 percent at both three and five years, rising to 94 percent when salvage surgery of local recurrences was included . Actuarial disease-free survival was 81 percent at both five and ten years. Radiation-induced morbidity was very low and the cosmetic outcome was considered at least satisfactory.

The principal adverse consequence associated with radiation therapy is the development of soft tissue atrophy at the site of irradiation.