const pptxgen = require("pptxgenjs");
const pres = new pptxgen();
pres.layout = "LAYOUT_16x9";
pres.title = "Carcinoma of the Cervix";
pres.author = "OB/GY Lecture Series";

// ── COLOR PALETTE ──────────────────────────────────────────────
const DARK_BG   = "1A1A2E";   // deep navy
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const ACCENT    = "E94560";   // crimson red
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const MUTED_TXT = "B0B8CC";   // muted blue-grey
const WHITE     = "FFFFFF";
const TEAL      = "0F7173";   // teal accent

// ── HELPER ─────────────────────────────────────────────────────
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// ══════════════════════════════════════════════════════════════
// SLIDE 1 — TITLE
// ══════════════════════════════════════════════════════════════
{
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    { text: "Epidemiology • HPV • Pathology • Staging • Management • Prognosis", options: { color: MUTED_TXT } }
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}

// ══════════════════════════════════════════════════════════════
// SLIDE 2 — OUTLINE
// ══════════════════════════════════════════════════════════════
{
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    ["01", "Introduction & Epidemiology"],
    ["02", "Etiology & Risk Factors (HPV)"],
    ["03", "Pathogenesis & Natural History"],
    ["04", "Histopathology & Gross Morphology"],
    ["05", "Clinical Features & Evaluation"],
    ["06", "FIGO Staging (2018)"],
    ["07", "Patterns of Spread & Lymph Nodes"],
    ["08", "Treatment — Surgery"],
    ["09", "Treatment — Radiation & Chemoradiation"],
    ["10", "Prognosis, Screening & Prevention"],
  ];
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}

// ══════════════════════════════════════════════════════════════
// SECTION 1 — EPIDEMIOLOGY
// ══════════════════════════════════════════════════════════════
sectionHeader("01  Epidemiology", "Global Burden & Incidence");

contentSlide("Epidemiology — Global Burden", [
  "Worldwide: 4th most common cancer in women; 2nd most common in developing countries",
  "USA: ~12,578 new cases / year (CDC 2014); 4,115 deaths",
  "Lifetime probability in the USA: 1 in 128 women",
  "3rd most common gynecologic neoplasm in the USA (behind uterine corpus & ovarian cancer)",
  "In developing countries, 60% of cervical cancers occur in women who have NEVER had a Pap test",
  "Worldwide incidence is declining due to effective screening programs",
  "Mean age at diagnosis: 47 years (bimodal peaks at 35–39 yrs and 60–64 yrs)",
]);

// ══════════════════════════════════════════════════════════════
// SECTION 2 — ETIOLOGY & RISK FACTORS
// ══════════════════════════════════════════════════════════════
sectionHeader("02  Etiology & Risk Factors", "HPV — The Causal Agent");

contentSlide("Role of HPV in Cervical Carcinogenesis", [
  "HPV detected in up to 99% of women with squamous cervical carcinoma",
  ">100 types of HPV; >30 can affect the lower genital tract",
  "15 high-risk HPV subtypes identified",
  "HPV 16 & 18 account for ~70% of all cervical carcinomas",
  "HPV 31, 33, 45, 52, 58 — additional high-risk subtypes",
  "HPV 6 & 11 — low-risk types (genital warts)",
  "HPV types 16 or 18 confer a 50-fold increase in risk for precancerous lesions",
]);

contentSlide("HPV Oncogenic Mechanism", null, {}, [
  { title: "E6 Protein", items: [
    "Binds and degrades p53 tumor suppressor",
    "Prevents cell cycle arrest",
    "Blocks cellular apoptosis",
    "Allows accumulation of DNA damage",
  ]},
  { title: "E7 Protein", items: [
    "Binds Retinoblastoma (Rb) protein",
    "Disrupts transcription factor E2F",
    "Causes unregulated cellular proliferation",
    "Both E6 + E7 are essential for malignant transformation",
  ]},
]);

// fix: pass cols properly
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});
slide_hpv_mech.addShape(pres.ShapeType.line, { x: 0.4, y: 0.9, w: 9.2, h: 0, line: { color: ACCENT, width: 1.5 } });
// E6 box
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  { text: "Prevents cell cycle arrest", options: { bullet: { code: "2022" }, color: LIGHT_TXT, fontSize: 14, fontFace: "Calibri", breakLine: true, paraSpaceBefore: 6 } },
  { text: "Blocks cellular apoptosis", options: { bullet: { code: "2022" }, color: LIGHT_TXT, fontSize: 14, fontFace: "Calibri", breakLine: true, paraSpaceBefore: 6 } },
  { text: "Allows accumulation of damaged DNA", options: { bullet: { code: "2022" }, color: LIGHT_TXT, fontSize: 14, fontFace: "Calibri", paraSpaceBefore: 6 } },
];
slide_hpv_mech.addText(e6, { x: 0.5, y: 1.75, w: 4.0, h: 3.2 });
// E7 box
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slide_hpv_mech.addText("E7 Protein", { x: 5.4, y: 1.15, w: 4.1, h: 0.55, fontSize: 18, bold: true, color: GOLD, fontFace: "Calibri" });
const e7 = [
  { text: "Binds Retinoblastoma (Rb) protein", options: { bullet: { code: "2022" }, color: LIGHT_TXT, fontSize: 14, fontFace: "Calibri", breakLine: true, paraSpaceBefore: 6 } },
  { text: "Disrupts transcription factor E2F", options: { bullet: { code: "2022" }, color: LIGHT_TXT, fontSize: 14, fontFace: "Calibri", breakLine: true, paraSpaceBefore: 6 } },
  { text: "Causes unregulated cellular proliferation", options: { bullet: { code: "2022" }, color: LIGHT_TXT, fontSize: 14, fontFace: "Calibri", breakLine: true, paraSpaceBefore: 6 } },
  { text: "Both E6 + E7 are ESSENTIAL for malignant transformation", options: { bullet: { code: "2022" }, color: GOLD, bold: true, fontSize: 14, fontFace: "Calibri", paraSpaceBefore: 6 } },
];
slide_hpv_mech.addText(e7, { x: 5.4, y: 1.75, w: 4.0, h: 3.2 });

contentSlide("Risk Factors for Cervical Cancer", null, [
  { title: "Behavioral / Epidemiological", items: [
    "Early age at first sexual intercourse (<16 yrs)",
    "Multiple sexual partners",
    "High parity",
    "Low socioeconomic status",
    "Cigarette smoking",
    "Oral contraceptive use (>5 years — controversial)",
    "No use of barrier contraception",
  ]},
  { title: "Infectious / Immunological", items: [
    "HPV 16 / 18 infection (primary cause)",
    "HSV-2 (cofactor)",
    "Chlamydia trachomatis (cofactor)",
    "HIV infection / AIDS (immune suppression)",
    "Chronic immune suppression (transplant, steroids)",
    "Absence of cervical screening / vaccination",
  ]},
]);

// ══════════════════════════════════════════════════════════════
// SECTION 3 — PATHOGENESIS
// ══════════════════════════════════════════════════════════════
sectionHeader("03  Pathogenesis & Natural History", "CIN → Invasive Carcinoma");

contentSlide("Transformation Zone & CIN", [
  "HPV infects basal cells of the transformation zone (junction of ecto- and endocervix)",
  "Squamocolumnar junction (SCJ): most vulnerable site for HPV integration",
  "CIN 1 (LSIL): mild dysplasia — often regresses spontaneously",
  "CIN 2 (HSIL): moderate dysplasia — treat with excision",
  "CIN 3 / CIS (HSIL): severe dysplasia / carcinoma in situ — mandatory treatment",
  "Progression from SIL to invasive carcinoma is variable and unpredictable",
  "Average time CIN 3 → Invasive cancer: 10–15 years (may be shorter)",
  "HPV infection is NECESSARY but NOT sufficient alone — additional mutations required",
]);

// ══════════════════════════════════════════════════════════════
// SECTION 4 — HISTOPATHOLOGY
// ══════════════════════════════════════════════════════════════
sectionHeader("04  Histopathology", "Types & Gross Morphology");

contentSlide("Histological Types of Cervical Cancer", [
  "Squamous cell carcinoma (SCC): most common — 80% of cases",
  "  • Develops in transformation zone; peak age ~45 years",
  "  • Well / moderately / poorly differentiated; keratin pearls in well-diff. tumours",
  "  • Neuroendocrine/small cell variant: morphologically resembles small cell lung Ca",
  "Adenocarcinoma: 15% of cases — incidence increasing",
  "  • Endocervical type (80%): mucin-producing columnar cells",
  "  • Variants: endometrioid, clear cell, minimal deviation (adenoma malignum)",
  "Adenosquamous carcinoma: ~5% — mixed squamous + glandular",
  "Small cell neuroendocrine carcinoma: <5% — very poor prognosis",
  "Others: sarcoma, malignant melanoma (rare)",
]);

contentSlide("Gross Morphology & Spread", [
  "Arise in transformation zone: range from microscopic foci → large exophytic masses",
  "Growth patterns: exophytic (cauliflower-like), endophytic (barrel cervix), ulcerative",
  "Barrel cervix: tumour encircles cervix, penetrates stroma — identified by palpation",
  "Desmoplastic stromal response: tongues and nests of squamous cells",
  "Risk of lymph node metastasis correlates with depth of invasion:",
  "  <3 mm depth → <1% risk of nodal metastasis",
  "  >3 mm depth → >10% risk of nodal metastasis",
  "Vascular space invasion (LVSI): important adverse prognostic factor",
]);

// ══════════════════════════════════════════════════════════════
// SECTION 5 — CLINICAL FEATURES
// ══════════════════════════════════════════════════════════════
sectionHeader("05  Clinical Features & Evaluation", "Symptoms, Signs & Investigations");

contentSlide("Clinical Features", null, [
  { title: "Early Disease (Preinvasive / Stage I)", items: [
    "Often ASYMPTOMATIC",
    "Detected on Pap smear screening",
    "Abnormal cytology → colposcopy",
    "Postcoital bleeding (most common symptom)",
    "Intermenstrual / irregular bleeding",
    "Watery / blood-stained vaginal discharge",
  ]},
  { title: "Advanced Disease (Stage II–IV)", items: [
    "Malodorous vaginal discharge",
    "Pelvic or back pain",
    "Obstructive uropathy / haematuria",
    "Rectal bleeding / constipation",
    "Lower limb oedema (lymphatic obstruction)",
    "Weight loss / cachexia",
    "Vesico-vaginal or recto-vaginal fistula",
  ]},
]);

contentSlide("Evaluation & Investigations", [
  "General physical examination: supraclavicular, axillary, inguinofemoral lymph nodes",
  "Speculum exam: inspect cervix and vaginal fornices; firm, expanded cervix is suspicious",
  "Rectal exam: assess parametrial involvement, pelvic wall fixation",
  "Pap smear: note — false-negative rate up to 50% in invasive cancer; never rely on a negative Pap in symptomatic patient",
  "Colposcopy + directed biopsy: confirms diagnosis; acetic acid highlights acetowhite lesions",
  "Cone biopsy / LEEP: for microinvasive disease",
  "Endocervical curettage (ECC): for glandular lesions",
  "Imaging: CT/MRI pelvis & abdomen (para-aortic nodes, parametria, bladder, rectum)",
  "PET-CT: lymph node mapping, distant metastases in bulky/advanced disease",
  "Cystoscopy / proctoscopy: if bladder/rectal involvement suspected",
  "Chest X-ray / CT: pulmonary metastases",
]);

// ══════════════════════════════════════════════════════════════
// SECTION 6 — STAGING (FIGO 2018)
// ══════════════════════════════════════════════════════════════
sectionHeader("06  FIGO Staging (2018)", "International Federation of Gynecology and Obstetrics");

tableSlide("FIGO Staging of Cervical Cancer (2018)", ["Stage", "Description"], [
  ["IA1", "Stromal invasion ≤3 mm depth; no LVSI"],
  ["IA2", "Stromal invasion >3 mm but ≤5 mm depth"],
  ["IB1", "Invasive carcinoma ≤2 cm in greatest dimension"],
  ["IB2", "Invasive carcinoma >2 cm but ≤4 cm"],
  ["IB3", "Invasive carcinoma >4 cm"],
  ["IIA1", "Involvement of upper 2/3 vagina, no parametrium, ≤4 cm"],
  ["IIA2", "Involvement of upper 2/3 vagina, no parametrium, >4 cm"],
  ["IIB", "Parametrial involvement, but not to pelvic wall"],
  ["IIIA", "Lower 1/3 of vagina involved; no extension to pelvic wall"],
  ["IIIB", "Extension to pelvic wall and/or hydronephrosis / non-functioning kidney"],
  ["IIIC1", "Pelvic lymph node metastasis only (imaging or pathology)"],
  ["IIIC2", "Para-aortic lymph node metastasis (imaging or pathology)"],
  ["IVA", "Invasion of bladder / rectal mucosa (biopsy proven)"],
  ["IVB", "Distant metastases (including peritoneal spread, supraclavicular LN)"],
]);

// ══════════════════════════════════════════════════════════════
// SECTION 7 — PATTERNS OF SPREAD
// ══════════════════════════════════════════════════════════════
sectionHeader("07  Patterns of Spread", "Direct Extension • Lymphatic • Haematogenous");

contentSlide("Patterns of Spread", null, [
  { title: "Direct Extension", items: [
    "Parametrium → pelvic wall",
    "Vagina (upper 2/3 → lower 1/3)",
    "Bladder (anterior) → IVA",
    "Rectum (posterior) → IVA",
    "Uterine corpus (upward)",
    "Sacro-uterine ligaments",
  ]},
  { title: "Lymphatic Spread (most important)", items: [
    "Obturator nodes (first echelon)",
    "External iliac & internal iliac nodes",
    "Common iliac nodes",
    "Para-aortic (lumbar) nodes",
    "Inguinal nodes (lower vaginal involvement)",
    "Supraclavicular nodes (stage IVB)",
  ]},
]);

tableSlide("Incidence of LN Metastasis by Stage", ["Stage", "Positive Pelvic Nodes (%)", "Positive Para-Aortic Nodes (%)"], [
  ["IA1 (≤3 mm)", "0.5%", "0%"],
  ["IA2 (>3–5 mm)", "4.8%", "<1%"],
  ["IB", "15.9%", "2.2%"],
  ["IIA", "24.5%", "11%"],
  ["IIB", "31.4%", "19%"],
  ["III", "44.8%", "30%"],
  ["IVA", "55%", "40%"],
]);

// ══════════════════════════════════════════════════════════════
// SECTION 8 — TREATMENT: SURGERY
// ══════════════════════════════════════════════════════════════
sectionHeader("08  Treatment — Surgery", "Stage-Based Surgical Options");

contentSlide("Surgical Treatment Options", [
  "Stage IA1 (no LVSI): Cone biopsy — adequate for fertility preservation",
  "Stage IA1 (with LVSI) / IA2: Simple (extrafascial) hysterectomy OR cone biopsy",
  "Stage IA2 – IIA: Radical (Wertheim) hysterectomy + bilateral pelvic lymphadenectomy",
  "  • Removes uterus, upper vagina, parametrium, uterosacral/uterovesical ligaments",
  "  • Pelvic LN dissection is essential for staging and treatment",
  "Radical trachelectomy: Fertility-preserving option for Stage IB1 (tumour ≤2 cm)",
  "  • Removes cervix + parametrium; cervicoisthmic anastomosis",
  "Sentinel lymph node biopsy: minimise morbidity in early-stage disease",
  "5-year survival for Stage I: ~85% with radical hysterectomy or radiation (equivalent)",
]);

contentSlide("Prognostic Variables After Surgery (Stage IA2–IIA)", null, [
  { title: "High-Risk Features (Adjuvant Chemoradiation)", items: [
    "Positive pelvic lymph nodes",
    "Positive surgical margins",
    "Parametrial involvement",
    "→ Adjuvant cisplatin-based chemoradiation recommended",
  ]},
  { title: "Intermediate-Risk Features (Adjuvant Radiation)", items: [
    "Lymphovascular space invasion (LVSI)",
    "Large tumour size (>4 cm)",
    "Deep stromal invasion (>1/3)",
    "→ Consider adjuvant pelvic radiation",
  ]},
]);

// ══════════════════════════════════════════════════════════════
// SECTION 9 — RADIATION & CHEMORADIATION
// ══════════════════════════════════════════════════════════════
sectionHeader("09  Radiation & Chemoradiation", "Primary & Adjuvant Radiotherapy");

contentSlide("Radiation Therapy", [
  "Can be used in ALL stages of cervical cancer",
  "Two components: External Beam Radiation Therapy (EBRT) + Brachytherapy",
  "EBRT: pelvis (± para-aortic nodes); dose 45–50 Gy over 5 weeks",
  "Brachytherapy (intracavitary): local boost to cervix / parametria",
  "  Tandem + ring / ovoid applicators (LDR or HDR)",
  "IMRT (Intensity-Modulated Radiation Therapy): spares bowel and bladder; reduces late toxicity",
  "Stage IB3 / IIA2: Primary chemoradiation (preferred over surgery)",
  "Stage IIB – IVA: Definitive chemoradiation (cisplatin-based concurrent)",
  "Complications: radiation cystitis, proctitis, vaginal stenosis, bowel obstruction, fistulae",
]);

contentSlide("Concurrent Chemoradiation (CRT)", [
  "Cisplatin-based CRT is STANDARD OF CARE for locally advanced cervical cancer (Stage IIB–IVA)",
  "Cisplatin 40 mg/m² IV weekly during radiation (5–6 cycles)",
  "Chemoradiation superior to radiation alone — reduces risk of death by 30–50%",
  "Adenocarcinoma and adenosquamous: worse outcome with radiation alone; similar to SCC with CRT",
  "Bevacizumab (VEGF inhibitor): added to platinum-based chemotherapy for recurrent/metastatic disease",
  "Pembrolizumab (PD-L1+): FDA approved for recurrent/persistent cervical cancer",
  "Stage IVB / distant metastases: palliative chemotherapy ± immunotherapy",
]);

// ══════════════════════════════════════════════════════════════
// SECTION 10 — PROGNOSIS, SCREENING, PREVENTION
// ══════════════════════════════════════════════════════════════
sectionHeader("10  Prognosis, Screening & Prevention", "Survival • Pap Smear • HPV Vaccine");

tableSlide("5-Year Survival Rates by FIGO Stage", ["Stage", "5-Year Survival (%)"], [
  ["IA1", "~98%"],
  ["IA2", "~95%"],
  ["IB1", "~90%"],
  ["IB2–IB3", "80–85%"],
  ["IIA", "70–75%"],
  ["IIB", "60–65%"],
  ["IIIA", "45–50%"],
  ["IIIB", "35–40%"],
  ["IVA", "15–20%"],
  ["IVB", "<5%"],
]);

contentSlide("Cervical Cancer Screening (Pap Smear)", [
  "Pap smear (conventional or liquid-based cytology) — primary screening tool",
  "Screening schedule (USA, ACS 2020 guidelines):",
  "  • Start age 25 years",
  "  • Ages 25–65: Primary HPV test every 5 years (preferred)",
  "  • Co-testing (HPV + Pap): every 5 years (acceptable)",
  "  • Pap test alone: every 3 years (acceptable)",
  "  • Stop screening at age 65 if adequately screened and no CIN2+ in past 25 years",
  "Colposcopy with biopsy: for ASC-US (HPV+), LSIL, HSIL, ASC-H, AGC on Pap",
  "Bethesda System for reporting cytology: NILM, ASC-US, ASC-H, LSIL, HSIL, AGC, AIS",
]);

contentSlide("HPV Vaccination — Prevention", [
  "HPV vaccine is the most effective primary prevention for cervical cancer",
  "3 vaccines available:",
  "  • Cervarix (bivalent): HPV 16, 18",
  "  • Gardasil (quadrivalent): HPV 6, 11, 16, 18",
  "  • Gardasil-9 (9-valent): HPV 6, 11, 16, 18, 31, 33, 45, 52, 58",
  "Gardasil-9 efficacy: 97% for CIN 2/3, VIN 2/3, VAIN 2/3 in HPV-naïve individuals",
  "FDA approved age: 9–45 years (both males and females)",
  "Schedule: 2-dose (if age <15 at first dose) or 3-dose series",
  "Important: Vaccinated women MUST continue Pap smear screening — vaccine does not cover all HPV types",
]);

// ══════════════════════════════════════════════════════════════
// SPECIAL SITUATIONS
// ══════════════════════════════════════════════════════════════
sectionHeader("Special Clinical Situations", "Pregnancy • Recurrent Disease • Emergencies");

contentSlide("Cervical Cancer in Pregnancy", [
  "Most common gynaecologic malignancy in pregnancy",
  "Incidence: ~1 in 10,000 pregnancies",
  "Diagnosis: Pap smear, colposcopy, punch/cone biopsy are safe in pregnancy",
  "Stage IA1 in first trimester: defer treatment until foetal maturity",
  "Stage IA1 at term: vaginal delivery → definitive treatment post-partum",
  "Stage IB1 or greater, before 20 weeks: immediate treatment may be needed",
  "Stage IB1 or greater, after 20 weeks: delay until foetal maturity achievable (≥34 wks)",
  "Caesarean section preferred in invasive disease to avoid tumour dissemination",
  "NACT (neoadjuvant chemotherapy): option to delay delivery in selected cases",
]);

contentSlide("Recurrent Cervical Cancer & Emergencies", null, [
  { title: "Recurrent Disease", items: [
    "Central recurrence after surgery: radiation ± chemo",
    "Central recurrence after radiation: pelvic exenteration",
    "Pelvic exenteration: en bloc removal of uterus, vagina, bladder/rectum",
    "Palliative chemotherapy: cisplatin + paclitaxel ± bevacizumab",
    "Pembrolizumab: PD-L1+ recurrent/metastatic disease",
    "Median survival for recurrent disease: 7–12 months",
  ]},
  { title: "Oncological Emergencies", items: [
    "Acute haemorrhage: packing, embolisation, palliative RT",
    "Ureteral obstruction: ureteral stenting or nephrostomy",
    "Vesico-vaginal fistula: urinary diversion",
    "Recto-vaginal fistula: colostomy",
    "Bowel obstruction: surgical bypass or palliative care",
  ]},
]);

// ══════════════════════════════════════════════════════════════
// SUMMARY SLIDE
// ══════════════════════════════════════════════════════════════
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    "HPV (especially types 16 & 18) is the CAUSAL agent — E6 inactivates p53, E7 inactivates Rb",
    "SCC (80%) > Adenocarcinoma (15%) > Adenosquamous/Small cell",
    "FIGO 2018 staging: IA→IVB; lymph node status now included in IIIC",
    "Surgery (radical hysterectomy): Stage I–IIA; Chemoradiation: Stage IIB–IVA",
    "Cisplatin-based concurrent CRT: standard for locally advanced disease",
    "5-yr survival: Stage IA ~98% → Stage IVB <5% (highly stage-dependent)",
    "Prevention: Gardasil-9 vaccine (97% efficacy) + Pap smear screening from age 25",
    "Pap smear every 3 years (or HPV test every 5 years) from age 25–65",
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// ══════════════════════════════════════════════════════════════
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// ══════════════════════════════════════════════════════════════
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// ══════════════════════════════════════════════════════════════
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// ══════════════════════════════════════════════════════════════
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