Malignant Chest Wall Tumors: Complex Defects and Their Management-A Review of 181 Cases.

BACKGROUND: Chest wall tumors are a heterogeneous group of tumors that are managed by surgeons from diverse specialties. Due to their rarity, there is no consensus on their diagnosis and management. MATERIALS: This retrospective, descriptive analysis includes patients with malignant chest wall tumors undergoing chest wall resection. Tumors were classified as primary, secondary, and metastatic tumors. The analysis includes clinicopathological characteristics, resection-reconstruction profile, and relapse patterns. RESULTS: A total of 181 patients underwent chest wall resection between 1999 and 2020. In primary tumors (69%), the majority were soft tissue tumors (59%). In secondary tumors, the majority were from the breast (45%) and lung (42%). Twenty-five percent of patients received neoadjuvant chemotherapy, and 98% of patients underwent R0 resection. Soft tissue, skeletal + soft tissue, and extended resections were performed in 45%, 70%, and 28% of patients, respectively. The majority of patients (60%) underwent rib resections, and a median of 3.5 ribs were resected. The mean defect size was 24 cm2. Soft tissue reconstruction was performed in 40% of patients, mostly with latissimus dorsi flaps. Rigid reconstruction was performed in 57% of patients, and 18% underwent mesh-bone cement sandwich technique reconstruction. Adjuvant radiotherapy and chemotherapy were given to 29% and 39% of patients, respectively. CONCLUSIONS: This is one of the largest single-institutional experiences on malignant chest wall tumors. The results highlight varied tumor spectra and multimodality approaches for optimal functional and survival outcomes. In limited resource setting, surgery, including reconstructive expertise, is very crucial.

A phase II study of gemcitabine and docetaxel combination in relapsed metastatic or unresectable locally advanced synovial sarcoma.

Synovial sarcoma (SS) is one of the commonest non-rhabdomyosarcoma soft tissue sarcoma with limited treatment options in the relapsed and advanced settings. The combination of gemcitabine and docetaxel has demonstrated its role predominantly in leiomyosarcoma and pleomorphic sarcomas but has not been prospectively studied in SS. This trial assesses the efficacy, tolerability and quality of life (QoL) with this regimen in metastatic/unresectable locally advanced relapsed SS.Patients and methods This was a single-arm, two-stage, phase II, investigator-initiated interventional study among patients with metastatic or unresectable locally advanced SS who had progressed after at least one line of chemotherapy. Gemcitabine 900 mg/m2 on days 1 and 8 and docetaxel 75 mg/m2 on day 8 were administered intravenously every 21 days. The primary endpoint was 3-month progression-free rate (PFR); overall survival (OS), progression-free survival (PFS), overall response rate (ORR), safety and quality of life (QoL) constituted the secondary endpoints.Results Twenty-two patients were enrolled between March 2020 and September 2021 and the study had to be closed early due to slow accrual. The study population comprised of 18 (81.8%) patients with metastatic disease and 4 (18.2%) patients with locally advanced, unresectable disease. The most common primary sites of disease were extremity in 15 (68%) and the median number of lines of prior therapies received was 1 (range 1-4). 3-month PFR was 45.4% (95% CI 24.8-66.1) and ORR was 4.5%. Median progression-free survival (PFS) was 3 months (95% CI 2.3-3.6) and median OS was 14 months (95% CI 8.9-19.0). 7 (31.8%) patients experienced grade 3 or worse toxicities, including anemia (18%), neutropenia (9%) and mucositis (9%). QoL analysis demonstrated significant decline in certain functional and symptom scales, while financial and global health scales remained stable.Conclusion This is the first prospective study on the combination of gemcitabine and docetaxel performed specifically in patients with advanced, relapsed SS. Although the accrual of patients could not be completed as planned, the therapy did produce clinically meaningful outcomes and met its primary endpoint of 3-month PFR. This result, along with the manageable toxicity profile and stable global health status on QoL analysis, should encourage further studies.Trial registration This trial was prospectively registered under the Clinical Trials Registry of India on 26/02/2020 (Registration number: CTRI/2020/02/023612).

No Doppler Single Position-Lateral Intercostal Artery Perforator Flap (NDSP-LICAP): a Safe and Versatile Flap for Breast Oncoplasty in Resource-Limited Setting.

INTRODUCTION: The lateral intercostal artery perforator flap (LICAP) has emerged as one of the safest and less morbid flaps for lateral and central breast defects. We hereby describe a reproducible no Doppler single position (NDSP) technique to harvest it in single position without handheld Doppler, making it a versatile flap for lateral breast defects in resource-limited setting also. MATERIALS AND METHODS: With this technique, we performed a total of 22 LICAP turnover flaps over a period of 18 months from January 2020 to June 2021. In all 22 cases, the indication of flap was to fill the post-breast conservation surgery (BCS) defects in outer quadrant of breast. All LICAP flaps were harvested by surface marking of anatomical landmarks and without handheld Doppler. RESULTS: Out of 22 LICAP turnover flaps, thirteen were harvested for left breast and nine for right breast. The median width and length of the flap were 12.2 cm and 19.6 cm, respectively. The additional mean operative time was 41 min. All LICAP flaps survived well, and grade 1 Clavien-Dindo morbidity was documented in four cases. Mean hospital stay was 2.6 days. All patients received radiotherapy on their stipulated schedule. Early cosmetic outcome was good, and long-term outcomes are awaited. CONCLUSION: NDSP-LICAP flap is a workhorse for lateral breast defects. Precise knowledge of perforators and anatomical landmarks can be used for harvesting these flaps, thus avoiding ultrasound Doppler and dedicated training for perforator localization. This technique has short learning curve without the need for any plastic surgery training. The early cosmetic outcomes are good.

Profile of Pathogenic Mutations and Evaluation of Germline Genetic Testing Criteria in Consecutive Breast Cancer Patients Treated at a North Indian Tertiary Care Center.

BACKGROUND: The burden of hereditary breast cancer in India is not well defined. Moreover, genetic testing criteria (National Comprehensive Cancer Network [NCCN] and Mainstreaming Cancer Genetics [MCG] Plus) have never been validated in the Indian population. METHODS: All new female breast cancer patients from 1st March 2019 to 28th February 2020 were screened. Those providing informed consent and without previous genetic testing were recruited. Multigene panel testing (107 genes) by next-generation sequencing was performed for all patients. The frequency of pathogenic/likely pathogenic (P/LP) mutations between patients qualifying and not qualifying the testing criteria was compared and their sensitivity was computed. RESULTS: Overall, 275 breast cancer patients were screened and 236 patients were included (median age 45 years); 30 patients did not consent and 9 patients previously underwent genetic testing. Thirty-four (14%) women had a positive family history and 35% had triple-negative breast cancer. P/LP mutations were found in 44/236 (18.64%) women; mutations in BRCA1 (22/47, 46.8%) and BRCA2 (9/47, 19.1%) were the most common, with 34% of mutations present in non-BRCA genes. Patients qualifying the testing criteria had a higher risk of having a P/LP mutation (NCCN: 23.6% vs. 7.04%, p = 0.03; MCG plus: 24.8% vs. 7.2%, p = 0.01). The sensitivity of the NCCN criteria was 88.6% (75.4-96.2) and 86.36% (72.65-94.83) for MCG plus. More than 95% sensitivity was achieved if all women up to 60 years of age were tested. Cascade testing was performed in 31 previous (16/44 families), with 23 testing positive. CONCLUSIONS: The frequency of P/LP mutations in India is high, with significant contribution of non-BRCA genes. Testing criteria need modification to expand access to testing.

Health-related quality of life (HRQoL), anxiety, and depression in patients with desmoid type fibromatosis.

INTRODUCTION: Data on the impact of desmoid type fibromatosis (DTF) on emotional distress and health-related quality of life (HRQoL) is sparse. METHODOLOGY: In this prospective cross-sectional study, patients with DTF and healthy controls were asked to fill the EORTC QLQ-C30, GAD-7, and PHQ-9 questionnaires. The objectives were to determine HRQoL, anxiety, and depression in patients with DTF. RESULTS: Two hundred four subjects (102 DTF patients and 102 healthy controls) were recruited. The median age of DTF patients at recruitment into the study was 31 years (IQR, 25-37 years). There was a female preponderance with a male:female ratio of 1:1.83. Appendicular skeleton and abdomen sites were most commonly involved in 59% and 22.5% respectively. About half (54%) of patients were currently on sorafenib and 41% were under active surveillance. The mean global health status in DTF patients was 65.58 ± 22.64, significantly lower than healthy controls. Similarly, DTF patients scored low on all functional scales except cognitive functioning. The symptom scale showed a significantly higher symptom burden of fatigue, pain, insomnia, and financial difficulties. Anxiety and depression was observed in 39.22% and 50% of DTF patients respectively. DTF patients had higher rates of mild, moderate, and severe anxiety and depression compared to healthy controls. CONCLUSION: DTF patients have significant symptom burden, poor functioning, and heightened anxiety and depression as compared to healthy controls. HRQoL, anxiety, and depression should be routinely used to assess symptom burden and treatment efficacy in DTF patients.

Comparison of two forced air warming systems for prevention of intraoperative hypothermia in carcinoma colon patients: a prospective randomized study.

Hypothermia is common occurrence in patients undergoing colonic surgeries. We hypothesized that the underbody forced air warming blankets will be better than conventional over-body forced air warming blankets for prevention of hypothermia during laparoscopic colon surgeries. After ethics approval, sixty patients undergoing elective laparoscopic colon surgeries were randomly divided into two groups to receive warming by underbody forced air warming blanket (n = 30) or over-body forced air warming blanket (n = 30). In the operating room, epidural catheter was inserted and thereafter warming was started with the forced air warmer with temperature set at 44 °C. Intraoperatively core temperature (using nasopharyngeal probe), vitals, incidence of postoperative shivering and time to reach Aldrete Score of 10 in the postoperative period were recorded. The core temperature was higher with an underbody blanket at 60 min (36.1 ± 0.5 °C vs. 35.7 ± 0.5 °C, P = 0.005), 90 min (35.9 ± 0.5 °C vs. 35.6 ± 0.5 °C, P = 0.009), 120 min (35.9 ± 0.5 °C vs. 35.5 ± 0.4 °C, P = 0.007), and 150 min (35.9 ± 0.5 °C vs. 35.6 ± 0.4 °C, P = 0.011). In the post anesthesia care unit, the time to reach an Aldrete score of 10 was also less in the underbody blanket group (14.3 ± 2.5 min vs. 16.8 ± 3.6 min) (P = 0.003). However, there were no clinically meaningful differences in any outcome. Underbody and over-body blankets were comparably effective in preventing hypothermia in patients undergoing laparoscopic colorectal surgery under general anaesthesia.Trial registration CTRI (2019/06/019,576). Date of Registration: June 2019, Prospectively registered.

Feasibility and outcomes of cytoreductive surgery and HIPEC for peritoneal surface malignancies in low- and middle-income countries: a single-center experience of 232 cases.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has recently emerged as a viable management option for peritoneal surface malignancy (PSM). CRS and HIPEC is a complex, multidisciplinary and resource-intensive surgical procedure. It has a steep learning curve and is associated with significant morbidity and mortality. The expertise is mostly limited to few dedicated high-volume centers located in developed countries. We present a single institutional experience of 232 cases of CRS and HIPEC performed at a tertiary care cancer center in a low- and middle-income country (LMIC). METHODS: A multidisciplinary PSM program was initiated in 2015 at a high-volume public-sector tertiary care cancer center in North India catering largely to patients belonging to low- and middle-income groups. Perioperative protocols were developed, and a prospective structured database was created to capture data. All patients undergoing CRS and HIPEC between January 2015 and December 2020 were identified, and the data was retrospectively analyzed for clinical spectrum, surgical details, and perioperative morbidity and mortality. RESULTS: Two hundred and thirty-two patients underwent CRS and HIPEC during the study period. Epithelial ovarian carcinoma (56.5%) was the most common malignancy treated, followed by pseudomyxoma peritonei (18.5%), colorectal carcinoma (13.4%), and malignant mesothelioma (5.6%). Optimal CRS could be achieved in 94.4% of patients. Cisplatin and mitomycin were the most common drugs used for HIPEC. A total of 28.0% of patients had morbidity including deep vein thrombosis, subacute intestinal obstruction, sepsis, burst abdomen, lymphocele, urinoma, acute renal failure, and enterocutaneous fistula. The overall treatment-related mortality was 3.5%. CONCLUSIONS: Results of the current study indicate that it is feasible to establish a successful CRS and HIPEC program for PSM in government-funded hospitals in LMIC facing resource constraints. The most common indication for CRS and HIPEC were carcinoma of the ovary followed by pseudomyxoma peritonei and colorectal carcinoma. Overall morbidity and mortality in the current series are comparable to global standards, reported from high-income countries. A protocol-based multidisciplinary team approach, optimal patient selection, and surgical expertise can help achieve optimal outcomes in government-funded hospitals in LMIC.

Palliative Surgery for Advanced Cancer: Clinical Profile, Spectrum of Surgery and Outcomes from a Tertiary Care Cancer Centre in Low-Middle-Income Country.

OBJECTIVES: Palliative surgery for cancer plays an important role in the overall management, especially in low-middle countries with a significant burden of advanced cancers. There is a paucity of literature related to the field of palliative surgery. In this study, we present the clinical spectrum, profile of surgical interventions and outcomes of palliative surgical procedures performed at a tertiary cancer centre involving multiple organ systems. MATERIALS AND METHODS: A retrospective analysis of prospectively maintained surgical oncology database of a tertiary care cancer centre was performed. Patients fulfilling the criteria of palliative surgery were analysed for clinical spectrum, indications for surgery, palliative surgical procedures and post-operative outcomes. RESULTS: A total of 678 out of 8300 patients fulfilled the criteria for palliative surgery. Palliative surgical procedures were performed most commonly for gastro-oesophageal malignancies (36.4%) followed by colorectal cancers (24%) and breast cancer (12%). Palliative mastectomy was the most common procedure performed for advanced breast cancer and 7% of sarcoma patients had amputations. Symptom relief could be achieved in 80-90% of patients and post-operative morbidity was relatively high among hepatobiliary, gastrointestinal and gynaecological cancer patients. CONCLUSION: Globally, a significant number of cancer patients need palliative surgical intervention, especially in LMIC with a high burden of advanced cancers. Results of the current study indicate that gastrointestinal cancer patients constitute a major proportion of patients undergoing palliative surgery. Overall results of the current study indicate that excellent palliation can be achieved in majority of patients with acceptable morbidity and hospital stay.

Unraveling the Role of Palliative Surgery in the Era of COVID-19 Pandemic.

Palliative surgery forms an important pillar of palliative treatment to provide holistic care to cancer patients in the form of providing relief from pain, local control of disease, hemorrhage, and for the purpose of rehabilitation. During the COVID-19 pandemic, we report the successful management of two cases of colorectal cancer which came under the category of high priority and underwent palliative surgery to provide relief from pain.

Assessing the effectiveness of high frequency repetitive transcranial magnetic stimulation for post-mastectomy pain in breast cancer patients: A randomized controlled trial.

BACKGROUND: Post-mastectomy pain Syndrome (PMPS), characterized by chronic neuropathic pain stemming from intercostobrachial nerve lesions, presents a formidable clinical challenge. With the incidence of breast cancer surging, effective interventions for PMPS are urgently needed. To address this, we conducted this double-blind, placebo-controlled, randomized clinical trial to study the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) therapy over the motor cortex on pain, quality of life and thermal sensitivity in PMPS patients. METHODS: We delivered 15 rTMS sessions over three weeks in a cohort of 34 PMPS patients. These patients were allocated randomly to either rTMS therapy or sham therapy groups. Pain assessments, utilizing the Visual Analogue Scale (VAS) and Short Form McGill Pain Questionnaire (SF-MPQ), alongside quality-of-life evaluations through the Functional Assessment of Cancer Therapy-Breast (FACT-B), were recorded before and after the 15 sessions. Additionally, we assessed thermal sensitivity using Quantitative Sensory Testing (QST). RESULTS: Our findings demonstrate the superior efficacy of rTMS therapy (over sham therapy) in reducing VAS and SF-MPQ scores (p < 0.0001), improving physical (p = 0.037), emotional (p = 0.033), and functional well-being (p = 0.020) components of quality of life, as quantified by FACT-B. Our investigation also unveiled marked enhancements in thermal sensitivity within the rTMS therapy group, with statistically significant improvements in cold detection threshold (p = 0.0001), warm detection threshold (p = 0.0033), cold pain threshold (p = 0.0078), and hot pain tolerance threshold (p = 0.0078). CONCLUSION: The study underscores the profound positive impact of rTMS therapy on pain, quality of life, and thermal sensitivity in patients having PMPS, opening new avenues for pain management strategies.

Demographic and clinical profile of 1106 adult soft tissue sarcoma patients: A single institutional prospective database experience from India.

BACKGROUND: Adult soft tissue sarcomas (STS) are rare and diverse. Current management is based on limited literature from the West. Therefore, data from different geographical regions is required, including the low-middle-income countries. This is our experience managing adult sarcomas in the tertiary cancer center of North India. MATERIALS AND METHODS: This is a retrospective analysis of the structured sarcoma database of patients treated in the surgical oncology department between 1992 and 2020. The descriptive analysis includes demography, site distribution, diagnosis, histopathology variations, prior surgical interventions, and stage. RESULTS: A total of 1106 soft tissue sarcoma patients were treated in three decades. Age distribution was 13%, 43%, 31%, and 11% in <20, 21-40, and 41-60 and >60 years, respectively. The male-to-female ratio was 1.73. The anatomical distribution was 17%, 42%, 23%, 7%, 7%, and 3% in upper extremity, lower extremity, trunk, retroperitoneum, head and neck, and viscera, respectively. Overall, 49% of patients had undergone prior suboptimal surgeries at community hospitals. Common histology subtypes were synovial sarcoma (18%), undifferentiated pleomorphic sarcoma (UPS) (13%), dermatofibrosarcoma protuberans (12%), and liposarcoma (9%). A pathological discordance of 13% was identified between the initial and the final histologies. Overall, 61% of tumors were high-grade. Memorial Sloan Kettering Stages II and III were present in 33% and 35% of patients, respectively. CONCLUSIONS: This is one of the largest single institutional experiences of STS from the Asian population. Mostly young adults were affected with male preponderance. The lower extremity and trunk were common subsites. Frequent histologies were synovial sarcoma and UPS. A high rate of suboptimal surgical intervention at the community level and pathological discordance was noted. This study highlights the need to establish prospective structured databases for capturing quality information related to rare malignancies and providing insights for future research.

Feasibility of the ERAS (Enhanced Recovery After Surgery) Protocol in Patients Undergoing Gastrointestinal Cancer Surgeries in a Tertiary Care Hospital-A Prospective Interventional Study.

Enhanced Recovery After Surgery (ERAS) protocols have emerged as a promising approach to optimize perioperative care and improve outcomes in various surgical specialties. Despite feasibility studies on ERAS in various surgeries, there remains a paucity of research focusing on gastrointestinal cancer surgeries in the Indian context. The primary objective is to evaluate the compliance rate of the ERAS protocol and secondary objectives include the compliance rate of individual components of the protocol, the complications, the length of hospital stay, and the challenges faced during implementation in patients undergoing gastrointestinal cancer surgeries in our tertiary care cancer center. In this prospective interventional study (CTRI/2022/04/041657; registered on 05/04/2022), we evaluated 50 patients aged 18 to 70 years undergoing surgery for gastrointestinal malignancies and implemented a refined ERAS protocol tailored to our institutional resources and conditions based on standard ERAS society recommendations for gastrointestinal surgeries and specific recommendations for colorectal, pancreatic, and esophageal surgeries.Our study's mean overall compliance rate with the ERAS protocol was 88.54%. We achieved a compliance rate of 91.98%, 81.66%, and 92.00% for pre-operative, intraoperative, and post-operative components respectively. Fourteen (28%) patients experienced complications during the study. The median length of stay was 6.5 days (5.25-8). Challenges were encountered during the preoperative, intraoperative, and postoperative phases. The study highlighted the feasibility of implementing the ERAS protocol in a cancer institute, but specific challenges need to be addressed for its optimal success in gastrointestinal cancer surgeries. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-024-01897-y.

Internal jugular vein thrombosis: an uncommon presentation.

Internal jugular vein (IJV) thrombosis is a rare entity. It is usually secondary to various etiologies such as ovarian hyperstimulation, deep vein thrombosis of upper limbs, venous catheter, malignancy, trauma, infection, and neck surgery and hypercoagulable status. We report an unusual case of internal jugular vein thrombosis with cerebral sinus thrombosis, postpartum in a 22-year-old female patient who presented with a painful swelling on the left side of her neck. Diagnosis was established by color Doppler ultrasonography and magnetic resonance venography. Thorough evaluation of the patient revealed no etiological factor leading to thrombosis. Patient was treated with low-molecular-weight heparin.

Correlation of 18-fluorodeoxyglucose uptake values on PET-CT scan with histological prognostic markers in breast cancer.

BACKGROUND: Positron emission tomography-computed tomography (PET-CT) scan utilizes 18-fluorodeoxyglucose (18-FDG), based on the principle of higher glycolytic activity and reduced glucose-6-phosphatase levels in cancer cells. This imaging modality is usually advised in the metastatic evaluation of stage III breast cancer patients. The correlation of maximum standard uptake values of primary lesion with different pathological and molecular markers has not been studied extensively. METHODS: Retrospective analysis of the data was performed from our prospectively maintained breast cancer database. All the patients who had undergone 18-FDG PET-CT scan at initial evaluation for staging between June 2017 and April 2020 were included in the study. One-way ANOVA test or Student's t-test as appropriate was performed to assess the difference of means in maximum standard uptake values (SUVmax) of the primary lesion and axillary nodes with clinical stage, histological grade, molecular subtype. Bonferroni post hoc test was also applied. RESULTS: Out of 388 patients in the breast cancer database, 45 patients met inclusion criteria. There was a significant correlation of molecular subtype (p = 0.029) with SUVmax of the primary lesion. Higher primary SUVmax was associated with higher T stage (p = 0.01) and higher histological grade (p = 0.06). In each molecular subtype, there was an increase in mean SUVmax of the primary lesion with increasing histological grade and vice versa. CONCLUSIONS: SUVmax of the primary lesion in breast cancer patients reflects tumor biology. Higher SUVmax can predict patients with triple-negative breast cancers and higher grades in primary tumors. However, further large-scale validatory studies are essential.

Randomized Controlled Trial of Neoadjuvant Short-Course Radiotherapy Followed by Consolidation Chemotherapy Versus Long-Course Chemoradiotherapy in Locally Advanced Rectal Cancer: Comparison of Overall Response Rates.

BACKGROUND: Management of locally advanced rectal cancer (LARC) is evolving with current emphasis on the addition of chemotherapy to short course radiotherapy (SCRT). We primarily aimed to analyse the difference in overall response rates between SCRT with sequential chemotherapy and standard long-course chemoradiotherapy (LCCRT)in LARC. METHODS: After randomization, patients in arm A received 45 Gy in 25 fractions over 5 weeks with concurrent capecitabine while patients in arm B received 25 Gy in 5 fractions over 1 week followed by 3 cycles of CAPOX (capecitabine and oxaliplatin) chemotherapy. Clinical and radiological response assessment was made after the completion of neoadjuvant treatment, a week prior to surgery. Adjuvant chemotherapy was added to complete 6 months of peri-operative chemotherapy. Surgery was performed between 8 and 10 weeks of completion of radiation treatment in both arms. RESULTS: Of the 33 patients recruited in this study between February 2020 to July 2021, 17 patients were randomized to arm A and 16 to arm B. The rates of complete tumour regression were 23.1% in arm A versus 35.7% in arm B (p-value = 0.683). Pathological complete response (pCR) rate was 20% arm A versus 30% in arm B (0.446). A higher number of patients in arm B experienced grade 3 diarrhoea, whereas acute skin toxicity was seen only in arm A. SCRT had fewer treatment interruptions compared to LCCRT. CONCLUSIONS: SCRT followed by three cycles of CAPOX chemotherapy in the neoadjuvant setting is comparable to LCCRT in terms of tumour response. This may be a better alternative regimen with fewer treatment interruptions in a resource-limited setting.

HPV-Associated Squamous Cell Carcinoma of the Eyelid: Diagnostic Utility of p16 Immunohistochemistry and mRNA In Situ Hybridization.

BACKGROUND: High-risk (HR) Human papillomavirus (HPV) has been implicated in pathogenesis of squamous cell carcinomas (SCC) at several sites with mucocutaneous junctions, including the head and neck. SCC is the second most common eyelid malignancy. However, its association with transcriptionally active HR-HPV has not been adequately studied. METHODS: Two index cases of eyelid HPV-associated SCC are described in detail. A retrospective cohort of eyelid SCC was examined for p16 immunoexpression. Cases demonstrating p16 positivity or equivocal staining were subjected to high-risk HPV mRNA in situ hybridization (ISH). Quantitative real-time PCR (qPCR) was performed in mRNA ISH-positive cases for HPV genotyping. RESULTS: The two index patients were older adult females, with upper eyelid tumours. On histology, both tumours were non-keratinizing SCC with trabecular and nested architecture reminiscent of oropharyngeal HPV-associated non-keratinizing SCC, prompting p16 immunohistochemistry, which was positive. HR-HPV mRNA ISH was positive, and qPCR detected HPV16 in both cases. Three of 20 (15%) archival cases showed p16 immunopositivity and two (10%) showed equivocal staining. However, mRNA ISH was negative. All cases showing p16 immunostaining and lacking HR-HPV were keratinizing SCCs. Thus, 9% of all eyelid SCC examined demonstrated HR-HPV. CONCLUSION: The prevalence of HR-HPV in eyelid SCC is low in Indian patients. HPV-associated SCC may mimic commoner eyelid carcinomas as it lacks overt keratinization. In basaloid-appearing eyelid carcinomas, p16 immunopositivity should be followed by reflex HR-HPV mRNA ISH, as p16 immunohistochemistry alone has low specificity. The prognostic role, if any, of HPV association needs further evaluation.