Abstract
The aim of this study was to determine whether the presence and extent of lympho-vascular invasion (LVI) is prognostic in surgical stage I cervical squamous cell carcinoma (SCC).
All available tumor slides and/or paraffin blocks from 426 patients with stage I cervical SCC treated surgically with curative intent were collected from 18 institutions and retrospectively analyzed. Presence and extent of LVI (focal: <5 spaces, extensive: ≥5 spaces) were assessed on scanning magnification in large H&E slide sets in 366 cases. Progression-free survival (PFS) was calculated as the time from surgery to first progression or death or last follow-up whichever occurred first. Overall survival (OS) was defined as the time from surgery to death or last follow-up.
Clinico-pathologic and statistical analyses were performed on 97 patients with FIGO 2018 stage IA and 329 patients with stage IB SCC of the cervix. LVI, both focal and extensive, was more frequent in stage IB compared to stage IA (p<0.001). Patients with stage IB carcinomas with extensive LVI had worse PFS (HR 2.86) (95%CI 1.49, 5.49) (p-value 0.005) and OS (HR 2.88) (95%CI 1.38, 6.02) (p-value 0.012) compared to those with focal or no LVI. In stage IA, in contrast, the presence and extent of LVI did not associate with PFS (p-value 0.926) or OS. Extensive LVI was not statistically correlated with PFS and OS in substages IA1, IA2 or IB2. PFS (HR 3.7) (95%CI 1.61, 8.46) (p-value <0.001) and OS (HR 4.18) (95%CI 1.58, 11.04) (p-value=0.002) in stage IB1 and PFS (HR 7.78) (95%CI 0.87, 69.82) (p-value=0.039) in stage IB3 were diminished in the presence of extensive LVI.
In conclusion, in patients with FIGO stage I cervical SCC, the presence and extent of LVI has prognostic significance in stage IB carcinoma and quantifying LVI is recommended.
Keywords: squamous cell carcinoma, lymph node metastasis, lympho-vascular invasion, stage, prognosis
1. Introduction
Squamous cell carcinoma (SCC) represents 75–80% of all cervical cancers and its incidence and associated mortality are still increasing in low to middle income countries according to GLOBOCAN 20181-3. Regardless of histologic subtype, cervical cancer is staged worldwide using the International Federation of Gynecology and Obstetrics (FIGO) staging system, which is based on anatomical extent of disease4. In cervical cancer, FIGO stage is an important survival predictor as well as a guide for clinical management.
Vascular/lymphatic space involvement (LVI) does not change the FIGO stage but the 2023 NCCN guideline as well as ESGO/ESTRO/ESP guidelines take this parameter into account when determining clinical management for early-stage tumors4–6. For example, sentinel lymph node biopsy is applicable to stage IA cases (T1A1 and T1A2) with LVI, while lymph node staging is not necessary in its absence6,7. Similarly, stage IA1-IA2 carcinomas with LVI are treated with radical trachelectomy/hysterectomy and sentinel lymph node biopsy/pelvic lymphadenectomy5.
Our group recently studied a wide range of potentially prognostic clinicopathological factors in SCC patients treated with initial surgical management and found that the presence of extensive LVI independently predicted worse progression free survival (PFS)8. This is in line with other previous studies demonstrating that LVI is associated with worse outcomes and increases recurrence risk9–13. Pathologic quantification of LVI (extensive vs focal) further stratifies patient survival outcomes in patients with SCCs8. Extensive LVI is also an independent predictor of pelvic lymph node metastases (LNM) in endocervical adenocarcinomas13. Moreover, our group previously analyzed the prognostic implications of LVI and patterns of stromal invasion in FIGO surgical stages IA and IB1 endocervical adenocarcinomas (ECA) and found that both parameters were important prognosticators15.
The importance of LVI quantitation is now accepted for endometrial carcinoma with multiple studies reporting worse outcomes when substantial LVI is present16–18. This finding has recently been included in the FIGO 2023 staging system of endometrial cancer as well as in international clinical management guidelines19–21. However, the presence or extent of LVI is not part of the FIGO staging system for cervical cancer despite its impact on adjuvant treatment recommendations, and the importance of its extent is only now emerging4–6,9.
In the present study, we aimed to investigate the significance of LVI and its extent with respect to PFS and overall survival (OS) in surgical stage I patients with SCCs stratified by substage.
2. Material and method
2.1. Case selection
All available tumor slides and/or paraffin blocks from 721 patients with presumed early-stage cervical SCC, treated surgically, were collected from 18 institutions (Figure 1). The institutions and treatment time frames included the following: University of Medicine, Pharmacy, Science and Technology “George E Palade” of Targu Mures, Romania (8/19/2011–6/5/2015); Memorial Sloan Kettering Cancer Center, New York, USA (5/18/1992–7/2/2021); Vancouver General Hospital, Canada (2/1/2017–12/6/2019); Regional Institute of Oncology, Iasi, Romania (1/28/2012–9/10/2018); Ospedale Sacro Cuore Don Calabria, Negrar, Italy (11/27/1996–10/28/2021); Sahlgrenska University Hospital, Gothenburg, Sweden (3/9/2014–12/20/2021); University of Chicago, Chicago, USA (4/22/2010–5/10/2017); Jikei University School of Medicine, Tokyo, Japan (6/10/2009–7/10/2020); Wayne State University, Detroit, USA (5/29/2002–1/10/2019); Massachusetts General Hospital, Boston, USA (1/24/2001–3/5/2018), Universita degli Studi di Messina, Italy (12/13/2000–10/18/2021; Oncologic Institute, Lisbon, Portugal (11/9/2005–11/6/2008); Department of Pathology, Laboratory Medicine Program, University Health Network, Toronto, Canada (4/11/2011–5/23/2023); Hospital Universitari de Bellvitge-IDIBELL, Barcelona, Spain (1/21/2010–5/25/2016); Emory University School of Medicine, Atlanta, USA (5/18/2012–7/3/2022); A.C. Camargo Cancer Center, Sao Paulo, Brazil (9/22/2014–3/17/2020); First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic (12/10/2013–5/7/2019); University of California, San Diego, USA (12/1/2014–11/8/2021).
Figure 1:
Flow diagram of patient selection.
Institutional Review Board approval was obtained from each institution. Each patient had presumed 2018 FIGO early-stage cervical SCC (i.e. stages IA and IB) and managed with upfront surgery. The cases were collected with the following inclusion criteria: SCC confirmed on microscopic examination; surgically treated with cervical conization, loop electrosurgical excision procedure (LEEP), trachelectomy, or hysterectomy with or without lymph node dissection; and no oncologic treatment before surgery. Cases were excluded if SCC was only confirmed on biopsy; microscopic examination revealed another type of cervical carcinoma (adenocarcinoma, adenosquamous, etc); or the patient was treated with chemotherapy and/or radiotherapy prior to surgery. Cases were also excluded if they were clinically staged as FIGO 2018 stage I but at pathologic examination they presented with lymph node metastases (up-staged as stage III, 195 patients), parametrial involvement (up-staged as stage II, 59 patients) or vaginal extension (up-staged as stage II, 41 patients) (Figure 1).
2.2. Morphologic assessment
All hematoxylin-eosin (H&E) slides from the tumor (cervix, with a mean of 12 slides per case) that were available for review were re-examined by either the corresponding gynecologic pathologist at the institution where there were identified or by 2 expert gynecologic pathologists (SS and RAS) in order to confirm the histologic tumor type (SCC), based on 2020 WHO classification2.
In addition to the histologic tumor type, presence/absence, and extent of LVI was assessed, in all cases with a consensus of two experienced pathologists at a multiheaded microscope (SS and RAS). The presence of LVI was established when tumor cells or a tumor embolus was present in an endothelial-lined space within the cervical stroma, at or outside the invasive edge of the tumor. Intratumor LVI was not recorded. Immunohistochemical markers were not used to identify LVI8. Presence and extent/number of LVI (focal: <5 spaces, extensive: ≥5 spaces) were assessed at scanning magnification, and if necessary, high-power magnification, in aggreagate across all slides reviewed per case (with a mean of 12).
The following data were retrieved from clinical and pathological databases at each institution: age; postoperative 2018 FIGO tumor stage; HPV status, regional and/or remote LNM; parametrial and vaginal involvement, surgical and adjuvant treatment, presence of recurrence and recurrence site; and follow-up data.
2.3. Statistical analysis
Demographic and clinical parameters were summarized using frequency and percent. Association between LVI and other clinical factors s were tested using Fisher Exact test. Progression-free survival (PFS) was calculated as the time from surgery to first progression or death or last follow-up whichever occurred first. Overall survival (OS) was defined as the time from surgery to death or last follow-up. Patients were censored at last follow-up if they did not experience progression or death for PFS, or death for OS. Patients whose progression/death/follow-up information was missing were excluded from survival analyses. Median OS and PFS and survival rate at 5 year were estimated using Kaplan–Meier methodology. Due to limited event number in this early-stage cohort (i.e. many institutions had zero events), adjustment for clustering effect by institution could not be performed. Log-rank test or Log-rank test with permutation (if a variable had a level with < 3 events) were used when applicable to test for significant differences between groups. All p values are two-sided. p value <0.05 was considered statistically significant. All analyses were conducted in R v. 4.3.1 (https://www.R-project.org/)22.
3. Results
In total, 426 surgical stage I patients were included in the present study, 97 (23%) patients with stage IA disease and 329 (77%) patients with stage IB disease. By substage, 49 (12%) cases were stage IA1, 47 (11%) cases were IA2, 164 (39%) cases were IB1, 122 (29%) cases were IB2 and 39 (9.3%) cases were IB3. In 5 patients, substaging information was missing while in 60 patients, LVI information was missing (and were further excluded from the statistical analysis) ; the core dataset consists of 366 patients. 310 patients were included in a previously published study in which the significance of LVI was not stratified by substage8. Clinico-demographic data are presented in Table 1. 193 (53%) cases lacked LVI, while focal LVI was present in 88 (24%) cases and extensive LVI in 85 (23%) cases. Out of 366 cases that were reviewed for LVI, 9 cases were found to be HPVI (for both HR and LR-HPV by ISH method, performed in a previous study23. LVI was absent in 7 HPV-independent cases, while focal LVI was present in one HPV-independent case and extensive LVI was present in 1 HPV-independent case. No statistically significant relationship between HPV status and presence and extent of LVI could been identified due to the small number of HPV-independent cases included into this cohort.
Table 1:
Clinical and demographic data of the entire cohort of patients
| Characteristic | N = 426 |
|---|---|
| Age (median) | 44(21–92) |
| FIGO Substage | |
| IA1 | 49(12%) |
| IA2 | 47(11%) |
| IB1 | 164(39%) |
| IB2 | 122(29%) |
| IB3 | 39(9.3%) |
| Not available | 5 |
| FIGO Stage | |
| IA | 97(23%) |
| IB | 329(77%) |
| LVI | |
| No | 193(53%) |
| Focal | 88(24%) |
| Extensive | 85(23%) |
| Not available | 60 |
| Surgical Treatment | |
| Radical Trachelectomy | 29(6.8%) |
| Simple Hysterectomy | 21(4.9%) |
| Radical Hysterectomy | 245(58%) |
| LEEP | 124(29%) |
| Other | 6(1.4%) |
| Not available | 1 |
| Adjuvant Treatment | |
| None | 273(66%) |
| Radiotherapy | 51(12%) |
| Chemotherapy | 2(0.5%) |
| Chemo/radiotherapy | 89(21%) |
| Not available | 11 |
| HPV status | |
| HPV-associated | 282 (66%) |
| HPV-independemt | 9 (2%) |
| Not available | 135 |
Data distribution and association with presence and extent of LVI are shown in Table 2. LVI, both focal and extensive, was more frequent in stage IB compared to stage IA disease (p<0.001) (Table 2). 80 (28%) patients with stage IB disease presented with extensive LVI, while extensive LVI was only present in 5(5.9%) of stage IA patients. Focal LVI was present in 13(15%) patients with stage IA disease and 75(27%) stage IB patients.
Table 2:
Presence and extent of LVI in association with age, FIGO substage and treatment
| Characteristic | Patients with LVI data, N = 366 | No LVI, N = 193 | Focal LVI, N = 88 | Extensive LVI, N = 85 | p-value1 |
|---|---|---|---|---|---|
| Age (median) | 44(22–87) | 43(22–87) | 47(25–80) | 43(27–80) | 0.56 |
| FIGO Substage | <0.001 | ||||
| IA1 | 44(12%) | 41(93%) | 2(4.5%) | 1(2.3%) | |
| IA2 | 40(11%) | 25(63%) | 11(28%) | 4(10%) | |
| IB1 | 138(38%) | 69(50%) | 32(23%) | 37(27%) | |
| IB2 | 106(29%) | 40(38%) | 32(30%) | 34(32%) | |
| IB3 | 34(9.4%) | 14(41%) | 11(32%) | 9(26%) | |
| FIGO Stage | <0.001 | ||||
| IA | 85(23%) | 67(79%) | 13(15%) | 5(5.9%) | |
| IB | 281(77%) | 126(45%) | 75(27%) | 80(28%) | |
| Surgical Treatment | 0.54 | ||||
| Radical Trachelectomy | 21(5.8%) | 11(52%) | 5(24%) | 5(24%) | |
| Simple Hysterectomy | 19(5.2%) | 11(58%) | 4(21%) | 4(21%) | |
| Radical Hysterectomy | 219(60%) | 117(53%) | 45(21%) | 57(26%) | |
| LEEP | 100(27%) | 52(52%) | 30(30%) | 18(18%) | |
| Other | 6(1.6%) | 2(33%) | 3(50%) | 1(17%) | |
| Not available | 1 | 0 | 1 | 0 | |
| Adjuvant Treatment | <0.001 | ||||
| None | 238(66%) | 144(61%) | 48(20%) | 46(19%) | |
| Radiotherapy | 48(13%) | 22(46%) | 12(25%) | 14(29%) | |
| Chemotherapy | 1(0.3%) | 1(100%) | 0(0%) | 0(0%) | |
| Chemo/Radiotherapy | 72(20%) | 21(29%) | 28(39%) | 23(32%) | |
| Not available | 7 | 5 | 0 | 2 |
Kruskal-Wallis rank sum test; Fisher’s Exact Test for Count Data with simulated p-value (based on 2000 replicates); Fisher’s exact test
Patients with stage IB disease and extensive LVI had worse PFS (HR 2.86) (95%CI 1.49, 5.49) (p-value 0.005) and OS (HR 2.88) (95%CI 1.38, 6.02) (p-value 0.012) compared to those with focal or no LVI (Table 3, Figure 2). 5-year PFS was 91.3% in stage IB disease with no LVI, 83.7% in stage IB disease with focal LVI and 75.1% with extensive LVI. 5-year OS rate was 95.2% in stage IB disease without LVI, 93.7% in stage IB disease with focal LVI and 84.6% with extensive LVI. In stage IA carcinomas, in contrast, the presence and extent of LVI did not associate with PFS (p-value 0.926) or OS (Table 4; Figure 3). Extensive LVI was not statistically correlated with OS and PFS in substages IA1, IA2 or IB2 (Supplementary Tables 1-3, Supplementary Figures 1-3), while PFS (HR 3.7) (95%CI 1.61, 8.46) (p-value <0.001) and OS (HR 4.18) (95%CI 1.58, 11.04) (p-value=0.002) were worse in stage IB1 carcinomas with extensive LVI and PFS (HR 7.78) (95%CI 0.87, 69.82) (p-value=0.039) was worse in stage IB3 carcinomas with extensive LVI (Tables 5, 6, Figures 4–5).
Table 3.
PFS and OS among Stage IB patients (N=279)
| PFS Analysis | ||||||
|---|---|---|---|---|---|---|
| Variable | N | Prog/Death# | MedianPFS (months;95%CI) | 5Yr PFS rate (95%CI) | HR(95%CI) | LogRank-Pv |
|
LVI | ||||||
| No | 125 | 16 | 254(200-NE) | 91.3%(84.4–95.2%) | 1 | 0.005 |
| Focal | 75 | 15 | 205(135-NE) | 83.7%(72.4–90.6%) | 1.83(0.89–3.75) | |
| Extensive | 79 | 23 | 282(179-NE) | 75.1%(63.4–83.5%) | 2.86(1.49–5.49) | |
| OS Analysis | ||||||
| Variable | N | Death# | MedianOS(months;95%CI) | 5YrOS_rate(95%CI) | HR(95%CI) | LogRank-Pv |
|
LVI | ||||||
| No | 125 | 11 | 296(200-NE) | 95.2%(88.7–98%) | 1 | 0.012 |
| Focal | 75 | 9 | Not Reached | 93.7%(83.9–97.6%) | 1.56(0.64–3.79) | |
| Extensive | 79 | 20 | 282(179-NE) | 84.6%(73.9–91.2%) | 2.88(1.38–6.02) | |
NE=Not Estimatable
Figure 2:
Progression-free survival and overall survival among stage IB patients.
Table 4.
PFS and OS among Stage IA patients (N=84)
| PFS Analysis | ||||||
|---|---|---|---|---|---|---|
| Variable | N | Prog/Death# | Median PFS (months;95%CI) | 5Yr PFS rate (95%CI) | HR(95%CI) | LogRank-Pv |
|
LVI | ||||||
| No | 66 | 6 | Not Reached | 90.7%(79–96%) | – | |
| Focal | 13 | 1 | Not Reached | 91.7%(53.9–98.8%) | – | |
| Extensive | 5 | 0 | Not Reached | 100% | – | |
| LVI(Remove Extensive) | ||||||
| No | 66 | 6 | Not Reached | 90.7%(79–96%) | 1 | 0.926 |
| Focal | 13 | 1 | Not Reached | 91.7%(53.9–98.8%) | 0.94(0.11–7.84) | |
| OS Analysis | ||||||
| Variable | N | Death# | Median OS (months;95%CI) | 5Yr OS rate (95%CI) | HR(95%CI) | LogRank-Pv |
|
LVI | ||||||
| No | 66 | 4 | Not Reached | 94.1%(82.8–98.1%) | – | |
| Focal | 13 | 0 | Not Reached | 100% | – | |
| Extensive | 5 | 0 | Not Reached | 100% | – | |
Note1: P value is obtained using Log-Rank Test/Log-rank test with 5000 permutation time [1] if certain level event#<3
Figure 3:
Progression-free survival and overall survival among stage IA patients.
Table 5.
PFS and OS among Stage IB1 patients (N=137)
| PFS Analysis | ||||||
|---|---|---|---|---|---|---|
| Variable | N | Prog/Death# | Median PFS (months;95%CI) | 5Yr PFS rate(95%CI) | HR(95%CI) | LogRank-Pv |
|
LVI | ||||||
| No | 68 | 10 | 296(213.4-NE) | 90.4%(79.8–95.6%) | 1 | <0.001 |
| Focal | 32 | 3 | Not Reached | 92.7%(73.7–98.1%) | 0.77(0.21–2.86) | |
| Extensive | 37 | 15 | 282(63.5-NE) | 68.6%(50.5–81.3%) | 3.7(1.61–8.46) | |
| OS Analysis | ||||||
| Variable | N | Death# | Median OS (months;95%CI) | 5Yr OS rate (95%CI) | HR(95%CI) | LogRank-Pv |
|
LVI | ||||||
| No | 68 | 7 | 296(213-NE) | 94.9%(84.8–98.3%) | 1 | 0.002 |
| Focal | 32 | 2 | Not Reached | 100% | 0.8(0.16–3.99) | |
| Extensive | 37 | 13 | 282(109-NE) | 82.6%(65.3–91.8%) | 4.18(1.58–11.04) | |
Note1: Pvalue is obtained using Log-Rank Test/Log-rank test with 5000 permutation time [1] if certain level event#<3
NE=Not Estimatable
Table 6.
PFS and OS among Stage IB3 patients (N=34)
| PFS Analysis | ||||||
|---|---|---|---|---|---|---|
| Variable | N | Prog/Death# | Median PFS (months;95%CI) | 5Yr PFS rate(95%CI) | HR(95%CI) | LogRank-Pv |
|
LVI | ||||||
| No | 14 | 2 | 254.2(NE) | 92.9%(59.1–99%) | 1 | 0.039 |
| Focal | 11 | 6 | 28.7(11.5-NE) | 45.5%(16.7–70.7%) | 9.85(1.18–82.19) | |
| Extensive | 9 | 4 | Not Reached | 50.8%(15.7–78.1%) | 7.78(0.87–69.82) | |
| OS Analysis | ||||||
| Variable | N | Death# | MedianOS (months;95%CI) | 5Yr OS rate (95%CI) | HR(95%CI) | LogRank-Pv |
|
LVI | ||||||
| No | 14 | 1 | 254(NE) | 100% | 1 | 0.280 |
| Focal | 11 | 3 | Not Reached | 70.7%(33.7–89.5%) | 5.26(0.53–52.41) | |
| Extensive | 9 | 3 | Not Reached | 75%(31.5–93.1%) | 4.67(0.48–45.41) | |
Note1: Pvalue is obtained using Log-Rank Test/Log-rank test with 5000 permutation time [1] if certain level event#<3
NE=Not Estimatable
Figure 4:
Progression-free survival and overall survival among stage IB1 patients.
Figure 5:
Progression-free survival and overall survival among stage IB3 patients.
4. Discussion
Our study shows that, in patients with surgical FIGO stage I cervical SCC, the presence and extent of LVI has prognostic associations in stage IB cervical squamous cell carcinomas. This could not be documented in patients with stage IA carcinomas.
The presence and extent of LVI has recently been introduced as variables in the 2023 FIGO staging of cancer of the endometrium, a risk stratification tool19. The presence of LVI is one of the most robust indicators of increased risk of lymph node involvement, pelvic recurrence and distant metastasis, and in stage I endometrial cancer patients extensive LVI is the strongest predictor of recurrent regional and metastatic disease 16,17, 24–29. These values are now accounted for in the ESGO/ESTRO/ESP clinical management guidelines21.
In contrast to endometrial carcinoma, the significance of the extent of LVI has only recently begun to be explored in cervical SCC. The latest update of guidelines for cervical cancer management by ESGO/ESTRO/ESP accounts for LVI, but not its extent6. The same approach has been proposed by the ICCR guideline recommendations on reporting cervical cancer by pathologists30. Furthermore, neither the presence of LVI nor its extent is reflected in the latest FIGO staging for cervical cancer4. Praiss, et al, recently published that extensive LVI is associated with worse progression free survival and higher rates of LNM8. Our current study, combining newly acquired cases with those from the Praiss publication allowed us to validate our previous observations in a larger cohort and to determine whether the clinical significance of LVI varies within FIGO stage I substages. The present work has demonstrated that the presence and extent of LVI in patients with stage I cervical cancer can help predict survival outcomes for subsets of patients. Parenthetically, similar work has been performed for endocervical adenocarcinomas13.
Determining an evidence-based threshold in gynecologic pathology can be challenging at least in part because the biological behavior of any given tumor is multifactorial, and such thresholds should ideally be established based on studying large clinically annotated series. The present study used a well-documented cohort of surgical stage I SCCs retrieved from multiple international institutions with high-quality pathology review and robust data collection with long-term clinical outcome. We reviewed a mean of 12 slides per case in contrast to endometrial cancer studies where generally only 2–5 slides of tumor per case are available for microscopic examination. We aligned our criteria for extensive LVI with the 2023 FIGO staging of cancer of the endometrium, but recognize that even this value is somewhat arbitrary. Studies investigating the significance of extensive LVI in endometrial carcinoma have used values ranging from 3 or more foci to 5 or more 2,19,20,31–33. Defining extensive LVI by finding tumor emboli in 5 or more endothelial lined spaces in aggregate across all slides reviewed allowed us to reach conclusions regarding associations with clinical outcomes.
In this study, all cases were reviewed by experienced gynecological pathologists and in cases where LVI was difficult to be assessed or quantified, a consensus was reached without using immunohistochemical markers. To assess LVI in cervical cancer, we recommend using the definition provided in the methods section (tumor cells or a tumor embolus present in an endothelial-lined space within the cervical stroma). Evaluation should be performed beyond the invasive tumor front. In difficult cases, the presence of an endothelial lining or adherent fibrin, absence of any stromal element, adherence of tumor cell groups to the side of the vascular space, and the contour of the intravascular component matching the contour of the vessels should be assessed8.
The study was limited by the retrospective nature of case collection, chart review, and pathology review. The data were collected from multiple centers where practice models and initial surgical management differed, and the analysis included cases that date back more than 3 decades during which time case work-up, initial surgical management, and adjuvant radiation techniques have evolved. There were relatively few stage IA cases with LVI, with even fewer events, which limits our confidence in drawing firm conclusions about the apparent lack of clinical significance of LVI in that setting. Lympho-vascular invasion in stage IA1 carcinomas is generally considered a significant clinical risk, at least regarding the presence of lymph node metastasis. However, in a study of stage IA cervical squamous cell carcinoma and adenocarcinomas from the National Cancer Database, encompassing 3239 patients from 2010–2015, the hazard ratio for death in patients with IA1 carcinomas with LVI was 1.05 and not significant (95% CI 0.45 to 2.45)34. Nevertheless, our data should be validated in a much larger population of patients.
5. Conclusions
Extensive LVI is more frequent in stage IB compared to stage IA, and LVI is prognostically significant in stage IB, with extensive LVI portending worse survival outcomes. Consequently, quantifying LVI in patients with SCC is recommended.
Supplementary Material
SUPPLEMENTARY DATA
Supplementary data related to this article can be found at http:
sources of funding:
This research was funded in part by the National Institutes of Health (NIH)/National Cancer Institute (NCI) Cancer Center Support Grant P30 CA008748.
Footnotes
Conflicts of interest The authors state that there are no conflicts of interest to disclose.
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