Cervical Cancer: HPV, Screening and Treatment

Cervical Cancer: HPV, Screening and Treatment

Cervical cancer is the fourth most common cancer in women worldwide, with approximately 660,000 new cases and 350,000 deaths annually. It remains a leading cause of cancer death in low- and middle-income countries where screening programmes are inadequate. In China, cervical cancer is the second most common gynaecological cancer, with approximately 120,000 new cases annually — though incidence is declining as HPV vaccination and cervical screening programmes expand.

Cervical cancer is unique among major cancers in having a well-defined, detectable pre-malignant phase (cervical intraepithelial neoplasia — CIN) lasting years to decades before progression to invasive cancer, and in being almost entirely caused by a single preventable infection: human papillomavirus (HPV). This makes cervical cancer the most preventable major cancer — through vaccination and screening, the vast majority of cases are entirely avoidable.

HPV — The Cause of Cervical Cancer

Human papillomavirus (HPV) is a double-stranded DNA virus with over 200 subtypes. Genital HPV infection is the most common sexually transmitted infection worldwide — approximately 80% of sexually active individuals will be infected at some point in their lifetime.

High-risk HPV types (oncogenic) — capable of causing cervical cancer:

• HPV 16 and 18: responsible for approximately 70% of all cervical cancers worldwide
• Other high-risk types (31, 33, 45, 52, 58): responsible for a further 20%

Low-risk HPV types (non-oncogenic): HPV 6 and 11 cause genital warts but do not cause cervical cancer.

Most HPV infections are transient — the immune system clears them within 1–2 years. Persistent infection with a high-risk HPV type (present for >12–18 months) drives transformation of the cervical squamocolumnar junction (transformation zone) → cervical intraepithelial neoplasia (CIN) → invasive cancer. This progression typically takes 10–20 years, providing an extended window for detection and treatment.

Cervical Intraepithelial Neoplasia (CIN — Pre-Cancer)

CIN is graded by the depth of epithelial involvement:

Grade	Description	Progression to Cancer	Management
CIN 1	Mild dysplasia; lower third of epithelium	~1% progress to cancer; 60% regress spontaneously	Active surveillance (repeat colposcopy/cytology)
CIN 2	Moderate dysplasia; lower two-thirds	~5% progress; 40% regress	Treatment usually recommended (LLETZ)
CIN 3	Severe dysplasia / carcinoma in situ; full thickness	Can progress to invasive cancer if untreated; estimates depend on population and follow-up	Treatment recommended; method and timing selected individually, including pregnancy considerations (e.g. LLETZ or cone excision)

Progression and regression percentages in this table are study estimates that depend on the population and follow-up period; they are not individual risk predictions.

Risk Factors

• Sexual behaviour: earlier age of first intercourse, multiple sexual partners — both increase HPV exposure risk
• Persistent high-risk HPV infection — the essential cause
• Smoking — cofactor that impairs local cervical immune clearance of HPV; doubles risk of progression from CIN to cancer
• Immunosuppression — HIV infection markedly increases risk and accelerates progression; organ transplant recipients; long-term steroids
• Long-term oral contraceptive pill (>5 years) — modest association; biological mechanism unclear
• High parity — multiple pregnancies; possibly hormonal or immune-related
• Lack of cervical screening — the dominant preventable risk factor in developed countries; most invasive cervical cancers occur in women who have never been screened

HPV Vaccination — Primary Prevention

HPV vaccination is the most impactful cervical cancer prevention measure. Examples of HPV vaccines include the following; product authorisation and availability vary by country:

• Gardasil 9 (9-valent): targets HPV 6, 11, 16, 18, 31, 33, 45, 52, 58 — targets HPV types responsible for approximately 90% of cervical cancer cases; product choice depends on local authorisation and individual eligibility
• Gardasil (4-valent): HPV 6, 11, 16, 18
• Cervarix (bivalent): HPV 16, 18; cross-protection against 31, 33, 45

Timing: maximum efficacy when given before first sexual exposure (age 9–13 as primary target); effective and recommended up to age 26 routinely; may be given up to age 45 with individual decision-making. Does not protect against infections already acquired.

WHO lists Walrinvax, manufactured in China, as a bivalent HPV vaccine. It is not a 9-valent vaccine. Confirm the exact vaccine product, locally authorised age range, dosing schedule and current availability with the vaccination provider before booking.

Evidence: Countries with high-coverage adolescent HPV vaccination programmes (Australia, UK, Scandinavia) are already observing >80% reduction in CIN2+ and dramatic declines in invasive cervical cancer incidence in vaccinated cohorts.

Cervical Screening

Despite vaccination, screening remains essential — vaccines don't protect against all HPV types, and women vaccinated as adults may have been exposed before vaccination.

Pap Smear (Cervical Cytology)

A spatula or brush collects cells from the transformation zone; prepared as a liquid-based cytology (LBC) sample. The result is reported using the Bethesda System:

• NILM (Negative for Intraepithelial Lesion or Malignancy) — normal
• ASC-US (Atypical Squamous Cells of Undetermined Significance) — reflex HPV testing
• LSIL (Low-grade Squamous Intraepithelial Lesion) — correlates with CIN 1
• HSIL (High-grade Squamous Intraepithelial Lesion) — correlates with CIN 2–3; urgent colposcopy
• ASC-H — atypical cells where HSIL cannot be excluded
• AGC (Atypical Glandular Cells) — may indicate adenocarcinoma in situ or endocervical/endometrial pathology

HPV Co-testing / Primary HPV Testing

HPV testing detects the presence of high-risk HPV DNA. Primary HPV screening (with or without cytology) is now the preferred modality in most guidelines for women over 25–30 due to higher sensitivity for CIN2+:

• HPV negative: very low risk; 3–5-year intervals between screens
• HPV positive, cytology negative: 12-month repeat co-test or colposcopy
• HPV 16/18 positive: immediate colposcopy regardless of cytology (highest risk)

China screening guidelines: population-based cervical cancer screening expanded significantly — combination HPV + cytology co-testing is increasingly available; screening target for women aged 35–64.

Colposcopy and Biopsy

Colposcopy is the investigation of abnormal smear or HPV results. A colposcope (binocular microscope) provides magnified visualisation of the cervix after application of acetic acid (acetowhite change identifies abnormal areas) and Lugol's iodine (iodine-negative areas are suspicious). Targeted biopsies are taken from abnormal-appearing areas.

Colposcopic findings are graded by density of acetowhite change, margin sharpness, and vascular patterns (punctation, mosaic, atypical vessels).

Management depends on the referral result, biopsy findings and previous history. Normal colposcopy does not automatically mean return to routine screening. The clinician should provide a risk-based follow-up plan; invasive cancer requires oncology referral.

Symptoms of Invasive Cervical Cancer

Early-stage cervical cancer is often asymptomatic — another reason screening is essential.

Symptoms of invasive disease:

• Abnormal vaginal bleeding — the most common symptom; postcoital bleeding (after sex) is the classic presentation; intermenstrual bleeding; postmenopausal bleeding
• Vaginal discharge — watery, mucoid, or blood-stained; may be malodorous (necrotic tumour)
• Pelvic pain — as tumour invades surrounding structures
• Haematuria or rectal bleeding — tumour invasion of bladder or rectum (advanced disease)
• Leg swelling — lymphoedema from pelvic lymph node involvement
• Ureteric obstruction — renal impairment with bilateral ureteric compression in advanced disease

Staging (FIGO 2018)

Stage	Broad extent of disease
IA	Microscopic invasion up to 5 mm deep
IB	Confined to the cervix, with invasion deeper than 5 mm
IIA	Upper vagina, without parametrial involvement
IIB	Parametrial involvement
IIIA	Lower third of vagina
IIIB	Pelvic wall involvement or tumour-related hydronephrosis/nonfunctioning kidney
IIIC	Pelvic or para-aortic lymph nodes
IVA	Adjacent pelvic organs
IVB	Distant spread

This is a simplified staging overview, not a prognosis calculator.

Staging investigations: MRI pelvis (parametrial and nodal assessment, most important); CT chest/abdomen/pelvis (distant metastases); PET-CT (lymph node involvement, most sensitive).

Treatment

Treatment of Pre-Cancer (CIN 2–3)

LLETZ (Large Loop Excision of the Transformation Zone) — also called LEEP (Loop Electrosurgical Excision Procedure). An electrically heated wire loop excises the transformation zone and CIN under local anaesthesia as an outpatient procedure. Provides both diagnosis (histological assessment of excision margins) and treatment.

• Cure rate for CIN 2–3: approximately 90–95%
• Follow-up after treatment for CIN 2–3 requires ongoing surveillance. A single negative HPV test does not automatically permit routine screening; the schedule depends on results, history and the applicable guideline.
• Risk of pre-term birth in subsequent pregnancy — LLETZ removes cervical stroma; large excisions or repeat LLETZ carry a small increased risk of cervical incompetence

Cryotherapy / laser ablation — alternatives for CIN 1–2 in carefully selected cases (fully visible lesion, no glandular involvement); ablative rather than excisional — no histological specimen.

Cone biopsy (cold knife cone) — for adenocarcinoma in situ, glandular lesions, or large-volume CIN where LLETZ may not achieve clear margins; performed under general anaesthesia.

Stage IA1 (Micro-invasive) — Fertility-Preserving Options

• Cone excision may be sufficient for selected stage IA1 disease with clear margins and no lymphovascular invasion. Nodal assessment is a separate specialist decision.
• Hysterectomy may be an option when fertility preservation is not desired.

Stage IA2–IB1 — Early Localised Disease

Surgery and radiotherapy are options for selected early-stage disease. The extent of surgery, nodal assessment and fertility-preserving options depend on tumour size, pathology and individual risk; radical hysterectomy is not required for every early-stage cancer.

• Robotic or laparoscopic approach: LACC trial (2018) demonstrated inferior survival with minimally invasive radical hysterectomy vs open surgery — for patients with early-stage cervical cancer in whom radical hysterectomy is indicated, an open abdominal approach is the standard approach
• Radical trachelectomy — removes the cervix and parametria but preserves the uterine body, allowing future pregnancy; for carefully selected stage IA2–IB1 women desiring fertility preservation; available at specialist gynaecological oncology centres

Locally Advanced Disease — Individual Staging Matters

Concurrent chemoradiotherapy (CRT) combines pelvic external-beam radiotherapy, chemotherapy and brachytherapy for suitable locally advanced disease. The oncology team determines the regimen and any additional systemic treatment.

• Brachytherapy — radioactive source placed directly within the cervix/uterus (intracavitary) via applicators under imaging guidance; delivers high-dose conformal radiation to the tumour while limiting dose to bladder and rectum; essential component of curative radiotherapy
• Image-guided adaptive brachytherapy (IGABT) — using MRI to plan individualised brachytherapy; modern standard; superior tumour control and lower toxicity vs conventional brachytherapy

Prognosis depends on disease extent, tumour biology, treatment and general health; population outcomes do not predict an individual result.

Recurrent and Metastatic Cervical Cancer

Pelvic exenteration — extensive surgery tailored to the location and extent of the recurrence; the organs removed depend on the operation and may include the bladder and/or rectum in selected patients with central pelvic recurrence without distant metastasis; potentially curative in carefully selected patients.

Pembrolizumab plus chemotherapy, with or without bevacizumab was studied in KEYNOTE-826 for persistent, recurrent or metastatic disease. The US indication requires PD-L1 CPS ≥1. Treatment suitability and local authorisation must be checked; US approval does not establish availability in China.

Tisotumab vedotin is an antibody-drug conjugate used in some jurisdictions for recurrent or metastatic disease after chemotherapy. Confirm current local authorisation and eligibility with the treating oncologist.

Cervical Cancer Care in China

China's gynaecological oncology centres offer:

Before arranging cervical cancer care in China, ask the receiving clinical team to confirm:

• The vaccine product and appointment availability, or the appropriate screening and colposcopy pathway.
• Whether pre-cancer treatment, fertility-preserving surgery or other cancer surgery is appropriate.
• The radiotherapy and brachytherapy facilities required for the proposed plan.
• The exact immunotherapy product, indication, testing requirements and local availability; medicines in the same class are not automatically biosimilars.
• An itemised hospital quote and the separately agreed scope of PriumCare coordination.

Contact a PriumCare care navigator to arrange HPV vaccination, cervical screening, colposcopy, or cervical cancer treatment.

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Source for this targeted correction

• WHO Walrinvax product record.

• NCI cervical cancer treatment PDQ.

• ASCCP management guideline updates through 2023.

• FDA pembrolizumab prescribing information.

Editorial source correction: 25 October 2026. This targeted check addressed the flagged treatment, surveillance, product and availability claims, and removed unsupported numerical or comparative promises. It is not a clinical review of the whole article. No named medical reviewer is claimed. Original publication date is retained.

Targeted cervical pre-cancer, vaccine and surgery scope clarification

Editorial source check: 26 October 2026. This update checks only the CIN3 risk/treatment wording and table-estimate context, the vaccine-list and coverage denominators, and the scope of radical hysterectomy and pelvic exenteration described above. It is not a whole-article medical review, adds no named clinical reviewer, and retains the original publication date.

• NCI PDQ: interpreting cervical pre-cancer risk
• NCI: CIN treatment options and pregnancy considerations
• NHS: colposcopy and treatment options
• WHO: Walrinvax vaccine record
• WHO-hosted Gardasil9 product information
• NCI PDQ: radical hysterectomy candidate selection
• NHS: differing extents of pelvic exenteration