Key points
- Almost all cases of cervical cancer are caused by persistent infection with high-risk types of human papillomavirus (HPV), which is why this cancer is largely preventable [1].
- The HPV vaccine, especially when given before age 17, greatly reduces the risk of invasive cervical cancer [2, 3].
- HPV testing every 5 years provides greater protection against invasive cancer than the Pap smear alone [4, 5].
- In locally advanced disease, chemoradiation is the backbone of treatment, and adding immunotherapy or a short course of induction chemotherapy has improved overall survival [6, 7].
- The World Health Organization has designed a global strategy to eliminate cervical cancer as a public health problem [8, 9].
What is cervical cancer?
The cervix is the lower, narrow part of the uterus that opens into the vagina. Cervical cancer develops when cells in this area turn into cancer cells, usually over many years and after passing through precancerous stages (CIN lesions) [1]. Its two main tissue types are squamous cell carcinoma (the more common) and adenocarcinoma [1].
Each year, more than half a million women worldwide develop this disease and more than 300,000 die of it; about 90% of cases occur in low- and middle-income countries that do not have organized screening and vaccination programs [1]. In high-income countries, the incidence of and mortality from this cancer have fallen by more than half over the past 30 years following the introduction of screening programs [1].
HPV: the main cause
Human papillomavirus (HPV) is a very common virus that is spread through sexual contact, and most people are infected with it at some point in their lives. In most cases, the immune system clears the virus within one to two years. Only in a small proportion of women does infection with high-risk types (especially HPV 16 and 18) persist, and over the years it can progress to a precancerous lesion and then to cancer [1].
This long gap between infection and cancer offers a golden opportunity for prevention (vaccination) and for detecting and treating precancerous lesions (screening) [1].
Signs and symptoms
Precancerous lesions and very early cancers usually cause no symptoms; this is why regular screening is vitally important [1]. As the disease progresses, the following symptoms may appear [1]:
- Abnormal vaginal bleeding: after intercourse, between menstrual periods or after menopause
- Unusual, watery or foul-smelling vaginal discharge
- Pelvic pain or pain during intercourse
- In advanced stages: flank or leg pain, swelling of the legs, or urinary and bowel problems
When should I contact my doctor?
If you have any unusual vaginal bleeding — especially after sex, between periods or after menopause — or unusual discharge or pelvic pain that doesn’t go away, have it checked by a gynecologist. These symptoms are more often caused by something benign, such as an infection or a polyp, but the examination is simple and will give you peace of mind.
Risk factors, prevention and screening
The most important risk factor is persistent infection with high-risk HPV. Factors that make the infection more likely to persist or progress include [1]:
- Smoking
- A weakened immune system (for example, HIV infection or taking immunosuppressive medicines)
- Starting sexual activity at a young age and having multiple sexual partners
- Multiple childbirths and long-term use of birth control pills
- And most important of all: not having regular screening
HPV vaccine: proven and safe
In a nationwide Swedish study of more than one and a half million girls and women, the quadrivalent HPV vaccine was associated with a substantial reduction in the risk of invasive cervical cancer; in women vaccinated before age 17, the adjusted incidence rate ratio was 0.12 (that is, about an 88% reduction in risk) [2]. In England’s national vaccination program, too, the rate of cervical cancer in girls who received the vaccine at ages 12 to 13 was 87% lower than in the unvaccinated group [3].
The randomized KEN SHE trial in Kenya showed that even a single dose of the bivalent or nonavalent vaccine prevents persistent HPV 16/18 infection with 97.5% efficacy, a finding that has paved the way for simpler and cheaper vaccination programs [10].
Screening: HPV test and Pap smear
Screening can detect precancerous lesions years before they turn into cancer. There are two main methods: the Pap smear (cytology), which looks for abnormal cells, and the HPV test, which checks for the presence of high-risk viruses [11].
Follow-up of four large European trials showed that HPV-based screening provides 60 to 70% greater protection against invasive cancer than cytology, and that the screening interval can be extended to at least 5 years [5]. A meta-analysis also showed that PCR-based HPV testing on a sample the woman collects herself (self-sampling) is almost as accurate as a sample taken by a doctor and helps reach women who are screened less often [12]. In the American Cancer Society’s 2026 update, collection by a doctor is still preferred, but a self-collected vaginal sample is acceptable for average-risk women aged 25 to 65; in that case, after a negative result, the test is repeated every 3 years (instead of every 5 years) [22].
| Age group | USPSTF (2018) [11] | American Cancer Society (2020, updated 2026) [4, 22] |
|---|---|---|
| Under 21 years | Screening not recommended | Screening not recommended |
| 21 to 24 years | Pap smear every 3 years | Screening starts at age 25 |
| 25 to 29 years | Pap smear every 3 years | Primary HPV test every 5 years (preferred); or co-testing every 5 years or Pap smear every 3 years; self-collected HPV sample acceptable, repeated every 3 years |
| 30 to 65 years | Pap smear every 3 years, or HPV test every 5 years, or co-testing (HPV + Pap) every 5 years | Primary HPV test every 5 years (preferred); self-collected HPV sample acceptable, repeated every 3 years |
| Over 65 years | Stop if prior screening was adequate and there is no high risk | Stop after a negative HPV test (preferred) or negative co-test at ages 60 and 65; if these are not available, after three consecutive negative Pap smears with the last test at age 65; separate criteria for a history of abnormal results or immunosuppression |
Women at high risk (for example, with HIV infection, immunosuppression or a history of precancerous lesions) need a special screening schedule. After removal of the uterus and cervix for benign reasons, screening is not needed [11].
The World Health Organization’s strategy to eliminate cervical cancer
The World Health Organization (WHO) has set the goal of bringing cervical cancer incidence below 4 cases per 100,000 women per year, and to get there it has proposed the “90-70-90” targets to be met by 2030 [8, 9]:
- 90% of girls fully vaccinated against HPV by age 15;
- 70% of women screened with a high-performance test (such as the HPV test) by age 35 and again by age 45;
- 90% of women with precancerous lesions treated, and 90% of women with invasive cancer receiving appropriate treatment.
Modeling in 78 low-income and lower-middle-income countries showed that full implementation of this three-pronged strategy could reduce cervical cancer deaths by about 99% by 2120 and save the lives of more than 62 million women [9]. Adding screening twice in a lifetime to vaccination brings the time to elimination forward by 11 to 31 years [8].
Diagnosis and staging
Diagnostic pathway for cervical cancer
- 1
- 2
- 3
Clinical pelvic examination
Assessment of tumor size and its spread to the vagina or the tissues around the uterus (parametrium) [13].
- 4
Imaging
Pelvic MRI to assess local spread, and CT or PET-CT to evaluate the lymph nodes and distant metastases in more advanced disease [13].
- 5
FIGO 2018 staging
The revised FIGO staging allows imaging and pathology findings to be used; involvement of pelvic or para-aortic lymph nodes places the patient in stage IIIC [14].
| Stage | Brief definition |
|---|---|
| I | Tumor confined to the cervix; IB1: 5 mm to less than 2 cm, IB2: 2 to 4 cm, IB3: 4 cm or more [14] |
| II | Spread beyond the uterus, but not to the pelvic wall or the lower third of the vagina [14] |
| III | Involvement of the lower third of the vagina or the pelvic wall, hydronephrosis, or involvement of pelvic (IIIC1) or para-aortic (IIIC2) lymph nodes [14] |
| IV | Involvement of the bladder or rectal mucosa (IVA) or distant metastasis (IVB) [14] |
The full definitions are given in the official FIGO staging; this table is meant as a general overview.
Treatment by stage
Treatment options by stage
Precancerous lesions
Removal of the abnormal area with outpatient procedures such as LEEP or conization, or with ablative methods; these treatments prevent the lesion from turning into cancer [1].
Very early stages (IA–IB1)
Surgery; in women who wish to become pregnant, fertility-sparing procedures (conization or trachelectomy) may be possible [1, 13]. In the SHAPE trial, for small low-risk tumors, simple hysterectomy was not inferior to radical hysterectomy with respect to pelvic recurrence and caused fewer urinary complications [15].
Early stages (IB2 and IIA1)
Locally advanced (IB3 to IVA)
Metastatic or recurrent
Platinum- and paclitaxel-based chemotherapy with bevacizumab [17]; in PD-L1–positive tumors (CPS ≥1), with the addition of pembrolizumab [18]. Adding atezolizumab to the same regimen, with no need for PD-L1 testing, is another option with a survival benefit [19]. In later lines: single-agent pembrolizumab for PD-L1–positive tumors not previously treated with immunotherapy [21, 23], trastuzumab deruxtecan for HER2-positive tumors [21, 24], single-agent chemotherapy, and a newer option, the antibody–drug conjugate tisotumab vedotin [20].
Supportive care
Pain control, psychological support, management of radiation side effects and attention to sexual health are an integral part of treatment at every stage [13].
What should I do after diagnosis?
Frequently asked questions
Does having HPV mean I will get cancer?
No. HPV infection is very common and in most people goes away on its own within a year or two. Only persistent infection with high-risk types may, over the years, turn into a precancerous lesion and cancer; that is why regular follow-up is important [1].
If I have had the HPV vaccine, do I still need screening?
Which is better, the HPV test or the Pap smear?
Is the HPV vaccine useful for boys too?
In men, HPV can also cause some cancers and genital warts, and men can carry and pass on the virus. In many countries, teenage boys are vaccinated too; talk with your doctor about it.
Can I get pregnant after treatment for cervical cancer?
What role does immunotherapy play in cervical cancer?
Immunotherapy is now part of standard treatment for advanced disease: both with chemoradiation in high-risk locally advanced disease [7] and with chemotherapy in metastatic or recurrent disease [18, 19]. Your doctor will decide whether it is right for you based on the stage and features of the tumor (such as PD-L1).
Evidence and recent advances (for physicians)
For physicians
Early-stage disease: surgery
The SHAPE trial showed that in low-risk tumors (mostly FIGO 2009 stage IB1), the three-year pelvic recurrence rate was 2.52% after simple hysterectomy and 2.17% after radical hysterectomy (noninferior), while urinary incontinence and urinary retention were significantly less frequent with simple hysterectomy [15].
In the LACC trial, minimally invasive radical hysterectomy (laparoscopic or robotic) was associated with lower 4.5-year disease-free survival (86.0% vs 96.5%) and lower three-year overall survival (93.8% vs 99.0%; HR for death 6.00) compared with open surgery [16]. Accordingly, the open approach is considered the standard for radical hysterectomy [13].
For physicians
Locally advanced disease
After two decades, two phase 3 trials have changed the standard of cisplatin-based chemoradiotherapy. In KEYNOTE-A18 (ENGOT-cx11/GOG-3047), 1060 high-risk patients (FIGO 2014 stage IB2–IIB with nodal involvement or stage III–IVA) received chemoradiotherapy with pembrolizumab or placebo (200 mg every 3 weeks for 5 cycles), followed by maintenance (400 mg every 6 weeks for 15 cycles); at the second interim analysis, the HR for death was 0.67 (95% CI: 0.50–0.90) and 36-month overall survival was 82.6% vs 74.8%. Potential immune-mediated adverse events occurred in 39% vs 17% [7]. The NCCN guideline (version 2.2026) considers adding pembrolizumab to chemoradiotherapy for selected patients with FIGO 2014 stage III–IVA disease, and has also included INTERLACE-based induction chemotherapy in its recommendations for stage IIB–IVA [21].
In INTERLACE, six weeks of weekly induction chemotherapy (carboplatin AUC2 and paclitaxel 80 mg/m²) before standard chemoradiotherapy increased 5-year progression-free survival from 64% to 72% (HR 0.65) and 5-year overall survival from 72% to 80% (HR 0.60); grade 3 or higher adverse events occurred in 59% vs 48% [6]. The population of this trial (mostly stage IIB) differs from that of KEYNOTE-A18, and there is no direct comparison of the two strategies.
Metastatic, persistent or recurrent disease
Since GOG 240, bevacizumab has been added to combination chemotherapy; in the final analysis, it increased median overall survival from 13.3 to 16.8 months (HR 0.77) [17]. In the 5-year follow-up of KEYNOTE-826, adding pembrolizumab to platinum-based chemotherapy (with or without bevacizumab) increased median overall survival from 16.5 to 28.6 months (HR 0.62) in patients with PD-L1 CPS ≥1 and from 16.8 to 26.4 months (HR 0.64) in all patients [18]. The NCCN guideline lists both chemotherapy-plus-bevacizumab regimens, with or without pembrolizumab (for CPS ≥1), among the preferred first-line options [21]. In BEATcc, atezolizumab plus bevacizumab and chemotherapy, without PD-L1 selection, improved progression-free survival (13.7 vs 10.4 months) and overall survival (32.1 vs 22.8 months) [19].
In the second or third line, in PD-L1–positive tumors not previously treated with immunotherapy, single-agent pembrolizumab produced an objective response rate of 14.6% with durable responses in the cervical cancer cohort of the phase 2 KEYNOTE-158 study [23], and NCCN lists it among the preferred options [21]. In HER2-expressing tumors (IHC 3+ or 2+), trastuzumab deruxtecan produced an objective response rate of 50% (20 of 40 patients; 75% in the 8 patients with HER2 IHC 3+) in the cervical cancer cohort of the phase 2 DESTINY-PanTumor02 study [24], and NCCN considers it for HER2-positive tumors [21]. Single-agent chemotherapy (such as vinorelbine, gemcitabine, irinotecan, pemetrexed or topotecan) is also used; the newer antibody–drug conjugate tisotumab vedotin reduced the risk of death by 30% compared with this same investigator’s-choice chemotherapy in the innovaTV 301 trial (median overall survival 11.5 vs 9.5 months; HR 0.70) [20].
Treatment regimens and dosing (for physicians)
Treatment regimens and doses: index10 regimens
Cisplatin (all cisplatin-containing regimens): Adequate hydration before each cisplatin dose with maintenance of urine output for 24 hours after the infusion, and antiemetics before and after the infusion, are required. In the presence of reduced creatinine clearance, myelosuppression or neuropathy, consider dose reduction or alternative treatment; grade 3–4 neuropathy is a reason for permanent discontinuation [27].
Carboplatin: The carboplatin dose is calculated with the Calvert formula: total dose (mg) = target AUC × (GFR + 25) [28].
Paclitaxel: Per the label, all patients are premedicated to prevent severe hypersensitivity reactions: dexamethasone 20 mg orally approximately 12 and 6 hours before the infusion, diphenhydramine 50 mg IV, and cimetidine 300 mg or ranitidine 50 mg IV 30 to 60 minutes before the infusion [29].
Bevacizumab (all bevacizumab-containing regimens): Do not administer for at least 28 days before and after major surgery (and until the wound has healed); monitor blood pressure and urine protein (withhold for proteinuria until it falls below 2 g; permanently discontinue for nephrotic syndrome); discontinue for gastrointestinal perforation, grade 4 fistula or any fistula involving an internal organ, grade 3–4 hemorrhage, and severe arterial thromboembolism [26]. In GOG 240, fistulas occurred in 15% of patients in the bevacizumab arm, all of whom had prior pelvic radiotherapy [17].
Pembrolizumab (all pembrolizumab-containing regimens): Check liver enzymes, creatinine and thyroid function at baseline and periodically. Dose reduction of pembrolizumab is not recommended: withhold for severe (grade 3) immune-mediated adverse reactions, and permanently discontinue for grade 4 reactions, recurrent grade 3 reactions requiring immunosuppression, or inability to taper corticosteroids to 10 mg or less of prednisolone per day within 12 weeks; permanently discontinue for grade 2 or higher myocarditis [25].
For physicians
Locally advanced disease: chemoradiotherapy and its add-ons
Chemoradiotherapy with weekly cisplatin (standard)
Locally advanced cervical cancer (IB3 to IVA), and stages IB2 and IIA1 when surgery is not appropriateCycle length: Weekly
Locally advanced cervical cancer (IB3 to IVA), and stages IB2 and IIA1 when surgery is not appropriate
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cisplatin | 40 mg/m² (in INTERLACE, maximum 70 mg per dose) | IV | Once weekly concurrent with external beam radiotherapy, 5 to 6 doses |
| Pelvic external beam radiotherapy | 45 to 50.4 Gy in 20 to 28 fractions | External beam radiotherapy | Concurrent with cisplatin |
| Brachytherapy | To a total equivalent dose in 2-Gy fractions (EQD2) of 78 to 86 Gy; in KEYNOTE-A18, at least 80 Gy (volume-based) or 75 Gy (point-based) | Intracavitary | After external beam radiotherapy |
In the landmark GOG trial, eligibility required serum creatinine ≤2 mg/dL, white blood cell count ≥3000/mm³ and platelets ≥100,000/mm³, and weekly cisplatin 40 mg/m² for 6 weeks improved survival compared with hydroxyurea [38]. Source for dosing and radiotherapy: the INTERLACE and KEYNOTE-A18 protocols [6, 33, 34].
Evidence: INTERLACE (GCIG) (2024), GOG (1999)
Pembrolizumab + chemoradiotherapy (KEYNOTE-A18)
FIGO 2014 stage III to IVA (FDA indication); the trial also enrolled stage IB2 to IIB with lymph node involvementEach drug’s schedule in the table
FIGO 2014 stage III to IVA (FDA indication); the trial also enrolled stage IB2 to IIB with lymph node involvement
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Concurrent with chemoradiotherapy: 5 cycles | |||
| Pembrolizumab | 200 mg (30-minute infusion) | IV | Day 1 every 3 weeks |
| Cisplatin | 40 mg/m² | IV | Once weekly for 5 or 6 weeks, with external beam radiotherapy and brachytherapy |
| Maintenance: 15 cycles | |||
| Pembrolizumab | 400 mg | IV | Day 1 every 6 weeks |
On days when both are given, pembrolizumab is administered before chemoradiotherapy. Source for the schedule: protocol NCT04221945 [33].
Weekly induction chemotherapy followed by chemoradiotherapy (INTERLACE)
FIGO 2008 stage IB1 node-positive, IB2, IIA, IIB, IIIB or IVA (70% of patients stage IIB); NCCN: stage IIB to IVACycle length: Weekly
FIGO 2008 stage IB1 node-positive, IB2, IIA, IIB, IIIB or IVA (70% of patients stage IIB); NCCN: stage IIB to IVA
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Induction: 6 weeks | |||
| Carboplatin | AUC 2 (maximum 270 mg) | IV | Days 1, 8, 15, 22, 29 and 36 |
| Paclitaxel | 80 mg/m² (maximum 162 mg) | IV | Days 1, 8, 15, 22, 29 and 36 |
| Then chemoradiotherapy | |||
| Cisplatin | 40 mg/m² (maximum 70 mg) | IV | Weekly, up to 5 doses, starting in the first week of radiotherapy |
| External beam radiotherapy + brachytherapy | 45 to 50.4 Gy in 20 to 28 fractions + brachytherapy to a total EQD2 of 78 to 86 Gy | Radiotherapy | Concurrent with cisplatin |
Cisplatin is started after blood counts have recovered from induction [34]. 92% of patients completed at least 5 induction cycles [6]. Source for doses and caps: protocol NCT01566240 [34].
Evidence: INTERLACE (GCIG) (2024)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Metastatic, persistent or recurrent disease: first line
Paclitaxel + cisplatin + bevacizumab (GOG 240)
First-line metastatic, persistent or recurrent disease; GOG performance status 0–1; no nonhealing wound or active bleeding; urine protein-to-creatinine ratio less than 1Cycle length: Every 21 days
First-line metastatic, persistent or recurrent disease; GOG performance status 0–1; no nonhealing wound or active bleeding; urine protein-to-creatinine ratio less than 1
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Paclitaxel | 175 mg/m² (3-hour infusion); or 135 mg/m² (24-hour infusion) | IV | Day 1 |
| Cisplatin | 50 mg/m² | IV | Day 1 or 2 |
| Bevacizumab | 15 mg/kg (30- to 90-minute infusion) | IV | Day 1 |
Platinum-free alternative: topotecan 0.75 mg/m² on days 1–3 + paclitaxel 175 mg/m² on day 1 (with or without bevacizumab), which was not superior to cisplatin–paclitaxel (HR for death 1.20) [39]. In KEYNOTE-826 and BEATcc, carboplatin AUC 5 on day 1 was also permitted instead of cisplatin [35, 36]. Source for doses and infusion durations: [17, 39, 41].
Evidence: GOG 240 (2017), GOG 240 (2014)
Pembrolizumab + paclitaxel and platinum ± bevacizumab (KEYNOTE-826)
First-line persistent, recurrent or metastatic disease with PD-L1 CPS ≥1 (by an approved test)Cycle length: Every 21 days
First-line persistent, recurrent or metastatic disease with PD-L1 CPS ≥1 (by an approved test)
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Pembrolizumab | 200 mg (or 400 mg every 6 weeks per the label) | IV | Day 1 every 3 weeks, before chemotherapy |
| Paclitaxel | 175 mg/m² | IV | Day 1 |
| Cisplatin or carboplatin | Cisplatin 50 mg/m² or carboplatin AUC 5 | IV | Day 1 |
| Bevacizumab (at the physician’s discretion) | 15 mg/kg | IV | Day 1 |
The most common grade 3–5 adverse events were anemia (30.3% vs 26.9%) and neutropenia (12.4% vs 9.7%) [40]. Source for dosing: protocol NCT03635567 [35].
Evidence: KEYNOTE (2026), KEYNOTE-826 (2023), KEYNOTE-826 (2021)
Atezolizumab + bevacizumab + paclitaxel and platinum (BEATcc)
First-line metastatic (IVB), persistent or recurrent disease that is untreated and not amenable to curative treatment; no PD-L1 testing requiredCycle length: Every 21 days
First-line metastatic (IVB), persistent or recurrent disease that is untreated and not amenable to curative treatment; no PD-L1 testing required
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Atezolizumab | 1200 mg | IV | Day 1 |
| Paclitaxel | 175 mg/m² | IV | Day 1 |
| Cisplatin or carboplatin | Cisplatin 50 mg/m² or carboplatin AUC 5 | IV | Day 1 |
| Bevacizumab | 15 mg/kg | IV | Day 1 |
Atezolizumab does not have a cervical cancer indication on its FDA label; the dose and schedule are taken from the trial protocol [19, 36]. Grade 3 or higher adverse events occurred in 79% vs 75%, and grade 1–2 diarrhea, arthralgia, pyrexia and rash were more frequent with atezolizumab [19].
Evidence: BEATcc (ENGOT-Cx10/GEICO 68-C/JGOG1084/GOG-3030) (2024)
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
Metastatic or recurrent disease: second line and beyond
Single-agent pembrolizumab (KEYNOTE-158)
Recurrent or metastatic disease with progression on or after chemotherapy, PD-L1 CPS ≥1; patients not previously treated with immunotherapy
Recurrent or metastatic disease with progression on or after chemotherapy, PD-L1 CPS ≥1; patients not previously treated with immunotherapy
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Pembrolizumab | 200 mg every 3 weeks or 400 mg every 6 weeks (30-minute infusion) | IV | Day 1 |
Grade 3–4 treatment-related adverse events occurred in 12.2% [23]. Monitor for and manage immune-mediated adverse events as with other pembrolizumab regimens [25].
Evidence: KEYNOTE-158 (2019)
Trastuzumab deruxtecan (DESTINY-PanTumor02)
Unresectable or metastatic HER2-positive (IHC 3+) tumors after prior systemic treatment with no satisfactory alternative options (FDA indication, accelerated approval); in the trial, IHC 3+ or 2+Cycle length: Every 3 weeks
Unresectable or metastatic HER2-positive (IHC 3+) tumors after prior systemic treatment with no satisfactory alternative options (FDA indication, accelerated approval); in the trial, IHC 3+ or 2+
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Trastuzumab deruxtecan | 5.4 mg/kg (first infusion over 90 minutes, then 30 minutes if tolerated) | IV | Day 1 |
Do not substitute for trastuzumab or trastuzumab emtansine; premedication to prevent nausea and vomiting is required. Interstitial lung disease (ILD): Promptly evaluate new respiratory symptoms, and permanently discontinue the drug for grade 2 or higher ILD. Assess blood counts before each dose and LVEF before initiation and periodically [31]. Across the whole study, drug-related ILD occurred in 10.5% of patients [24].
Evidence: DESTINY-PanTumor02 (2024)
Single-agent chemotherapy (innovaTV 301 control-arm options)
Recurrent or metastatic disease after first-line combination therapyEach drug’s schedule in the table
Recurrent or metastatic disease after first-line combination therapy
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| One of the following | |||
| Topotecan | 1 or 1.25 mg/m² | IV | Days 1–5, every 21 days |
| Vinorelbine | 30 mg/m² | IV | Days 1 and 8, every 21 days |
| Gemcitabine | 1000 mg/m² | IV | Days 1 and 8, every 21 days |
| Irinotecan | 100 or 125 mg/m² | IV | Weekly for 4 weeks, every 42 days |
| Pemetrexed | 500 mg/m² | IV | Day 1, every 21 days |
Pemetrexed: folic acid 400 to 1000 mcg orally daily from 7 days before the first dose until 21 days after the last dose; vitamin B12 1 mg IM one week before the first dose and then every 3 cycles; and dexamethasone 4 mg orally twice daily on the day before, the day of and the day after the infusion [32]. The objective response rate with these drugs in the trial was 5.2% [20]. Source for dosing: protocol NCT04697628 [37].
Tisotumab vedotin (innovaTV 301)
Recurrent or metastatic cancer with progression on or after chemotherapy (second or third line)Cycle length: Every 3 weeks
Recurrent or metastatic cancer with progression on or after chemotherapy (second or third line)
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Tisotumab vedotin | 2 mg/kg (maximum 200 mg for body weight of 100 kg or more), 30-minute infusion | IV | Day 1 |
Ocular toxicity warning: Eye examination (visual acuity and slit lamp) before initiation and before each cycle for the first 9 cycles; ophthalmic corticosteroid drops, one drop in each eye before each infusion and then three times daily for 72 hours; ocular vasoconstrictor drops immediately before the infusion; cold eye packs during the infusion; lubricating eye drops throughout treatment and for 30 days after the last dose; avoid contact lenses. Dose reductions: 1.3 mg/kg, then 0.9 mg/kg; permanently discontinue if 0.9 mg/kg is not tolerated [30]. Grade 3 or higher adverse events occurred in 52.0% and treatment discontinuation due to toxicity in 14.8% [20].
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
Scientific evidence
Key studies
10 itemsPembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 trial
Induction chemotherapy followed by standard chemoradiotherapy versus standard chemoradiotherapy alone in patients with locally advanced cervical cancer (GCIG INTERLACE): an international, multicentre, randomised phase 3 trial
Simple versus Radical Hysterectomy in Women with Low-Risk Cervical Cancer
Minimally Invasive versus Abdominal Radical Hysterectomy for Cervical Cancer
Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240)
Pembrolizumab Plus Chemotherapy for Cervical Cancer: An Exploratory Analysis of the KEYNOTE-826 Randomized Clinical Trial
Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study
Efficacy and Safety of Trastuzumab Deruxtecan in Patients With HER2-Expressing Solid Tumors: Primary Results From the DESTINY-PanTumor02 Phase II Trial
Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial
Tisotumab Vedotin as Second- or Third-Line Therapy for Recurrent Cervical Cancer
Clinical guidelines
3 itemsCervical Cancer, Version 2.2026, NCCN Clinical Practice Guidelines In Oncology
Self-collected vaginal specimens for human papillomavirus testing and guidance on screening exit: An update to the American Cancer Society cervical cancer screening guideline
ESGO/ESTRO/ESP Guidelines for the management of patients with cervical cancer - Update 2023
References
41 referencesShow all references, 27 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
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- 4
- 5
- 6
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- 9
- 10Efficacy of Single-Dose Human Papillomavirus Vaccination among Young African Women
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- 12Detecting cervical precancer and reaching underscreened women by using HPV testing on self samples: updated meta-analyses
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- 15Simple versus Radical Hysterectomy in Women with Low-Risk Cervical Cancer
- 16Minimally Invasive versus Abdominal Radical Hysterectomy for Cervical Cancer
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- 22Self-collected vaginal specimens for human papillomavirus testing and guidance on screening exit: An update to the American Cancer Society cervical cancer screening guideline
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- 26AVASTIN (bevacizumab) injection, for intravenous use: Prescribing Information
- 27CISPLATIN for injection, for intravenous use — Prescribing Information
- 28CARBOplatin Injection — Prescribing Information
- 29Paclitaxel Injection USP — Prescribing Information
- 30TIVDAK (tisotumab vedotin-tftv) for injection, for intravenous use: Prescribing Information
- 31ENHERTU (fam-trastuzumab deruxtecan-nxki) for injection, for intravenous use: Prescribing Information
- 32ALIMTA (pemetrexed) for injection, for intravenous use: Prescribing Information
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- 37Tisotumab Vedotin vs Chemotherapy in Recurrent or Metastatic Cervical Cancer (innovaTV 301) — study record (NCT04697628)
- 38Concurrent Cisplatin-Based Radiotherapy and Chemotherapy for Locally Advanced Cervical Cancer
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