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Lip cancer: A 5-year review in a tertiaryreferral centre*

D. Casal, L. Carmo, T. Melancia, C. Zagalo*, O. Cid, J. Rosa-Santos

Head and Neck Surgery Department, Instituto Portugues Oncologia de Lisboa Francisco Gentil, Rua Prof. Lima Basto,1099-023 Lisbon, Portugal

Received 27 October 2009; accepted 22 December 2009

KEYWORDSLip Cancer;Lip Tumour;Reconstruction;Recurrence;Mortality

Summary Introduction: Lip cancer is second only to skin cancer in terms of frequency in thehead and neck region. Surgery is the treatment of choice for most of these cancers. Althoughthere are several strategies to reconstruct lip tumours after tumour ablation, scarce attentionhas been paid to the impact of the specific reconstructive modality on recurrence and survival.Patients and methods: A retrospective review of 228 patients treated for lip cancer in theHead and Neck Surgery Department of the Portuguese Institute of Oncology Francisco Gentil,Lisbon, Portugal, from 1993 to 2000 with at least 2 years of follow-up was conducted. All thecases were evaluated for demographic features, tumour characteristics, lip reconstructivesurgery used and recurrence and survival.Results: There were 184 male and 44 female patients (4:1 ratio), with an average age of67.6� 13.3 years. Most tumours were squamous cell carcinomas (94.7%), and were locatedin the lower lip (99.5%). Squamous cell carcinomas were well differentiated in 70.8% of cases.Tumour size and neck staging were strongly correlated (Pearson’s coefficient of 0.805;p< 0.001). Microscopical signs of neuroinvasion or lymphatic invasion were associated anincreased risk of death due to cancer (chi-square Z 18.5; df Z 3; p Z 0.016). The differentstrategies used for lip reconstruction after tumour ablation did not differ significantly in theprobability of later recurrence or death.Conclusions: Our data seem to lend support to the classical view that the most significantaspect of lip cancer surgery is tumour ablation, and that this is not affected by the subsequentreconstructive strategy. Hence, this seems to indicate that experienced surgeons are rightlynot willing to compromise complete excision of the tumour for the sake of an easier or betterreconstruction.ª 2009 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published byElsevier Ltd. All rights reserved.

* This work has not been presented elsewhere.* Corresponding author. Servico de Cirurgia de Cabeca e Pescoco, Instituto Portugues Oncologia de Lisboa Francisco Gentil, Rua Prof. Lima

Basto 1099-023 Lisbon, Portugal. Tel.: þ351 919350242.E-mail address: czagalo1@sapo.pt (C. Zagalo).

1748-6815/$-seefrontmatterª2009BritishAssociationofPlastic,ReconstructiveandAestheticSurgeons.PublishedbyElsevierLtd.All rightsreserved.doi:10.1016/j.bjps.2009.12.022

Journal of Plastic, Reconstructive & Aesthetic Surgery (2010) 63, 2040e2045

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Oral cancer is a serious and growing problem in many partsof the world. Oral and pharyngeal cancer, groupedtogether, is the sixth most common cancer worldwide.1 In2004, there were 67 000 new cases registered in thecountries of the European Union (EU). In general, in the EU,oral and pharyngeal cancer occupy the 7th position.2

Squamous cell carcinoma (SCC) of the lower lip is a commonmalignant tumour comprising 25e30% of all oral cancers.3

In the head and neck region, SCC of the lip is second only toskin cancer in terms of frequency.4

Surgery is the treatment of choice for most of thetumours of the lip. It is clear from the literature that full-thickness resection of the tumour is the surgical procedureindicated.3 As conspicuous as these lesions might be, mostlip cancers are 1e2 cm in size when finally diagnosed andthus require a full-thickness resection of the skin, muscleand underlying mucosa to allow a safe surgical margin.5

The upper and lower lips constitute a distinct anatomicunit that is the principal feature of the lower face, therebyplaying a major role in facial appearance and function.Even though the first description of lip reconstruction datesback to at least 1000 BC in the eastern Sanskrit writings ofSusruta,6 reconstruction of the lips still represents a signif-icant challenge to the reconstructive surgeon who seeksexcellence in restoration of the aesthetics and functions ofthese unique structures.7The functional aspects often takeprecedence over the aesthetic ones, namely the ability tomaintain oral competence, maximum oral aperture,mobility and sensation, if possible.

Although numerous reconstructive possibilities havebeen devised and are currently used,7,8 scant attention hasbeen paid to the impact of various reconstruction modali-ties on recurrence and survival. In fact, it is generallyaccepted that lip-cancer recurrence and survival isdependent only on cancer-related factors and on thesurgical and adjuvant therapy used. However, Papadopou-los et al. have recently demonstrated in a large series of lipcancer patients that surgical excision followed by directrepair was associated with a higher 5-year recurrence ratethan vermillectomy or tumour excision followed by recon-struction using several types of flaps.9

Even though a few relatively large series have been pub-lished recently regarding the follow-up of lip cancerpatiens,4,9 little attention has been paid to the impact of thespecific reconstructive modality used on recurrence andsurvival. Therefore, the aim of this work is not only tocontribute to a better characterisation of the lip-cancerpopulation, but also to try to determine if any of the recon-structive options after lip cancer ablation is superior in termsof long-term probabilities of recurrence and survival.

Patients and methods

We conducted a retrospective review of the patientsreferred to the Head and Neck Surgery Department of thePortuguese Institute of Oncology Francisco Gentil (Lisbon,Portugal) with the diagnosis of lip cancer, from 1993 to2000, and at least 2 years of follow-up. Patients’ medicalrecords were used as the source of data for this study. Onlypatients with histological confirmation of lip cancer wereincluded. We obtained a sample of 228 patients. For each

case, the following features were recorded: age, sex, sizeand location of the tumour, tumour, node, metastasis (TNM)status at presentation, histological diagnosis and micro-scopical characteristics of the tumour, width of excisionmargin, type of reconstruction performed, postoperativetreatment, the presence of recurrence and the time torecurrence, mortality and time of follow-up. Comparisonsbetween variables were made after stratifying for tumourhistological subtype.

Analysis of the data was performed using the statisticalpackage software SPSS 16.0 (SPSS Inc., Chicago, IL, USA).

Results

A total of 228 patients with lip cancer were included in thestudy. There were 184 male (80.7%) and 44 female (19.3%)patients. The male-to-female ratio was 4:1. Patient ageranged from 28 years to 98 years with an average value of67.6� 13.3 years. The peak incidence was in the 61e70years group for males, and >81 years for females (Figure 1).

Regarding location of the tumour, the lower lip was themost frequently affected (218; 95.6%), followed by theupper lip (6; 2.6%), the lower lip and commissure (3; 1.3%)and in one patient, the lower and upper lips, as well as thecommissure were involved at presentation (0.4%).

When the patients first came to the Clinic, the largestdiameter of the tumour was on average 2.07� 1.49 cm,varying from 0.3 cm to 9.0 cm. The distribution of post-surgical TNM status is depicted in Table 1. Most tumourswere either stage I (68.6%) or stage II (21.0%), stage III andIV being represented in only 5.3% and 4.0% of the patients,respectively. There was a strong positive correlationbetween the tumour size at presentation and the neckstaging (Pearson’s coefficient of 0.805; p< 0.001). Nosignificant association was found between age, sex and siteor size of the tumour.

Histologically, the tumour was a squamous cell carci-noma (SCC) in 94.7% of cases (216), a basal cell carcinoma(BCC) in 4.4% (10) and a leiomyosarcoma in 0.9% (two) ofcases. SCC was exclusively found in the upper lip in onepatient, whereas the lower lip was involved in theremaining cases (99.5%). Basal cell carcinoma cases wereevenly distributed by upper and lower lip (five cases each).

Pathological examination revealed that the averagehistopathological margin of excision was 0.5� 0.39 cm. In10 patients, there was epidermal dysplasia at least on oneside of the resection specimen.

0

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40

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60

<50 50-60 61-70 71-80 >81Age Groups

N

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Figure 1 Distribution of patients according to age and sex.

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The SCCs were considered well differentiated in 70.8%(153), moderately well differentiated in 27.8% (60) andpoorly differentiated in 1.4% (three) of cases. Only 3.5% oftumours (eight) were shown to demonstrate microscopicalsigns of great aggressiveness, namely perineural invasion(PNI) in 1.9% (four) and vascular and lymphatic invasion in0.9% (two) of the cases each. The presence of PNI andlymphatic invasion was found to be associated with a higherrisk of cancer death (chi-square Z 18.5; df Z 3; p Z 0.016).

Seventeen patients were subjected to neck dissection atthe time of surgical excision (7.45%). Neck dissection wasperformed because patients either showed preoperativeevidence of node involvement (three patients), or they hadT3 or T4 cancer (11 patients), or because they had preop-erative evidence of node involvement and T3 or T4 cancer(three patients). Of these, 12 underwent bilateral modifiedradical neck dissection (70.6%), four underwent bilateralsupra omo-hyoid neck dissection (23.5%) and one patientunderwent unilateral modified radical neck dissection(5.9%).

Different surgical techniques were used for lip recon-struction after tumour ablation: in 197 (86.8%) patients,a V-shaped wedge excision and direct repair was performed(Figures 3 and 4); inferiorly based nasolabial flaps to

reconstruct the lower lip in nine patients (4%); W-shapedwedge excision in seven patients (3.1%); Webster flaps inthree patients (1.3%); and V-shaped wedge excision andvermillionectomy in three patients (1.3%). Reconstructionwith pectoralis major myocutaneous flap was performed intwo patients (0.9%), because these two patients had T4tumours extending into the skin of the neck and, afterexcision of the tumour, the defect was very wide, encom-passing both the entire lower lip and the skin over themental region and also part of the anterior portion of theneck. Although one pectoralis major flap suffered partialskin necrosis, coverage of the defect was achieved in thetwo cases, without the need of additional surgical proce-dures. The Karapandzic flap (Figures 5 and 6), W-shapedwedge excision and vermillionectomy, Estlander flap,

0

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Local Recurrence Mortality Survival

Figure 2 Frequency of survival, mortality and recurrence foreach reconstructive modality.

Table 1 Distribution of postoperative TNM Staging inpatients with SCC and BCC

TNM Staging Histological Type Total

SCC BCC

T1N0M0 145 10 155T1N3M0 1 0 1T2N0M0 48 0 48T2N1M0 2 0 2T3N0M0 9 0 9T3N1M0 1 0 1T3N3M0 1 0 1T4N0M0 6 0 6T4N1M0 2 0 2

Total 215 10 225

Figure 3 Case 1. Photograph of a 63-year-old male witha Squamous Cell Carcinoma of the lower lip. The limits of theV-shaped wedge excision have been marked with a surgical skinmarker.

Figure 4 Case 1. Postoperative photograph of the patient inthe previous image after V-shaped wedge excision and directclosure were performed. Note that there was no significantmicrostomia.

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bilobed flap, ‘V to Y’ advancement flap and lateral cheekadvancement flap were also used for reconstruction in onepatient each (0.4%). Except for one of the pectoralis majorflaps that suffered partial necrosis, all other flaps surviveduneventfully.

The 10 patients with epidermal dysplasia at least in oneside of the resection specimen were informed about theincreased risk of developing a new neoplasia. Six of thesepatients decided to have a vermillionectomy, whereas four

patients (all 73 years old or older) declined a new surgery.In this last group of patients, periods between observationswere made shorter.

The average follow-up time was 62.1 months, rangingfrom 2 years to 10 years. Only two patients (0.9%) withsignificant medical co-morbidities were treated preopera-tively with radiotherapy. They had rapidly growing T4N0M0SCCs of the lower lip. After a 4- and 5-week course ofradiotherapy, tumour shrinkage was observed and definitivesurgery was undertaken. In the postoperative period 29patients were treated with radiotherapy (12.8%).

Seven patients (3.1%) were found to have insufficientsecurity margin in the resection specimen, and a wideningof the excision was performed. Due to neck metastasis, twopatients (0.9%) were submitted to modified radical neckdissection after the primary excision.

In general, local recurrence was observed in 29 patients(12.8%), the average time to recurrence being 35.1� 34.2months.Oneof thepatientswithepidermaldysplasia inat leastoneof themarginsof thesurgical specimenand inwhich furthersurgery was declined had a local recurrence 1 year after theprimary surgery. This recurrence was treated with a V-shapedwedge excision and direct repair. No further recurrence wasobserved. Figure 2 depicts the percentages of mortality,survival and local recurrence for each major reconstructivemodality used. Statistical analysis failed to reveal any relationbetween the reconstructiveoptionandthe riskof recurrenceordeath.However, asexpected,patients inwhich recurrencewasdetected had an increased risk of death (chi-square Z 37.4;df Z 1; p< 0.001). Mortality rate due to lip cancer in our serieswas 8.3% at 5 years (19).

Discussion

Reviewing the literature regarding lip cancer, we foundthat our series of 228 patients was one of the largest, beingsecond only to the following: Fitzpatrick’s10 with 361 cases;Zitsch et al.11 with an impressive record of 1252 cases;McCombe et al.12 with 323 patients, and Papodoulos et al.9

with 899 cases.Contrary to what has been reported by other authors,13

most of the SCCs in our series were found to be welldifferentiated (70.8%), and only in a minority of casesmoderately well differentiated (27.8%) and poorly differ-entiated (1.4%). This is in stark contrast to the 47.6%frequency of poorly differentiated SCCs of the lip ina recent series from Nigeria.13 This may be attributed to anearlier detection of tumours in primary care services inWestern countries compared with developing nations,which in turn allows treatment of lip cancer at an earlierstage of development. Another reason may be the factthat, in this series, patients were significantly younger thanin ours (58% of patients were under the age of 50 in theNigerian series compared with only 11% in our series).Finally, one cannot exclude that different environmentalexposure to carcinogens may also play a role.1

Although BCCs are said to develop almost exclusively onthe upper lip,11 we found five cases of BCC in the lower lip,corresponding to 50% of the all BCCs detected. However, asmost authors, we found SCC almost exclusively in thelower lip.

Figure 5 Case 2. Photograph of a 72-year-old male afterresection of a 2 cm-wide Squamous Cell Carcinoma of the lowerlip. The cutaneous incisions of the Karapandzic flap have beenmarked with surgical ink.

Figure 6 Case 2. Photograph of the patient in the previousimage, after reconstruction with a Karapandzic flap. Moderatemicrostomia was observed, but the aesthetical result wasacceptable.

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In our series, PNI was found postoperatively in only 1.9%of cases. This value is much lesser than the 5% described byDinehart and Pollack.14 It is known that for the head andneck regions, PNI occurs in 2e6% of cutaneous BCCs andSCCs and is associated with midface location, recurrenttumours, high histologic grade and increasing tumoursize.15 However, PNI may not be clinically or histologicallyapparent until the tumour has spread extensively.16,17

Further, it has been demonstrated that if special stainingfor PNI is not routinely performed on histologic specimens,the true incidence may be underestimated.18 Therefore, itis hardly surprising that various studies studying specificallythe incidence of PNI in patients with lip cancer haveproduced inconsistent results, varying from 2.1% to 5%.19e21

Consequently, we believe that the differences in the rate ofPNI in the different series and between our series andothers quoted above may be due mainly to patients’heterogeneity and methodological differences in the searchfor this parameter. In our study, the relative low rate ofPNI, which was specifically sought in histological sections ofthe operative specimens, may therefore be largelyexplained by the relative high incidence of well-differen-tiated tumours. However, we believe that evidence for PNIshould be always actively pursued, as it has been shown toconfer a high risk of recurrence and metastasis,16,17

therefore making the use of adjuvant therapy oftenadvisable.22

Interestingly, we found a strong correlation betweentumour size at presentation and clinical staging, as hadalready been described by others in a slightly smaller seriesof patients.4As clinical staging has been found to signifi-cantly affect 5-year survival,1 this underlines the need topromote early detection and treatment of lip cancer todecrease morbidity and mortality. In this context, the roleof dentists may be of paramount importance, allowing foran earlier diagnosis of lip cancer. Thus, it seems reasonablethat dental examinations should routinely include exami-nation of the lips by visual inspection and palpation.23

In a recent series of 899 lip-cancer patients, Papado-poulos et al. found that surgical excision followed by directrepair was the type of surgery associated with the highest5-year recurrence rate.9 The authors attributed thesefindings to the limited margin of adjacent normal tissue inthe group of surgical excision followed by direct repair, andrecommended further studies to confirm their findings.However, in contrast to the observation of Papadopouloset al., we failed to detect any statistical significantdifference in terms of recurrence and mortality betweenthe various options used to excise and reconstruct the lipafter tumour extirpation.

One may, however, argue that a larger series of patientscould prove that some of the quantitative differencesdetected in the various reconstructive strategies used werein fact statistically significant and, more importantly, clin-ically significant. However, the present data seem to lendsupport to the classical view that the most significantaspect of lip cancer surgery is tumour ablation, and thatthis is not affected by the subsequent reconstructivestrategy. Hence, this seems to indicate that experiencedsurgeons are rightly not willing to compromise completeexcision of the tumour for the sake of an easier or betterreconstruction.

Conflict of interest

None.

Funding

None.

Acknowledgements

The authors would like to thank Dr. Pedro Martins for providingthe photographs in clinical case 2 (Figures 5 and 6) illustratingreconstruction of the lip using the Karapandzic flap.

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