Prevention of cervical cancer: definitions

Levels of prevention

Key terms

• HPV vaccination: The vaccine contains no live virus. It is recommended before the onset of sexual activity. The 9-valent vaccine is the one currently available in the US. WHO guidance now supports a single-dose schedule for the primary target age group.
• Cytologic screening (Pap test): Cells are scraped from the transformation zone, stained by the Papanicolaou method and examined. It detects LSIL and HSIL before invasion.
• HPV DNA testing: It has higher sensitivity but lower specificity than the Pap test. It is not recommended under age 30 because transient infections are common, which makes positive results unreliable (Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 925-926).
• Colposcopy: After acetic acid is applied, abnormal epithelium turns white (aceto-white). Abnormal areas are biopsied.
• Treatment of precancer: Ablation (e.g., cryotherapy) or excision of high-grade lesions stops progression to invasive cancer.

Screening schedules

• Textbook schedule: The first smear is at age 21 (or within 3 years of sexual onset), then every 3 years. After age 30, women with normal cytology and a negative HPV test can be screened every 5 years by HPV testing alone or with cytology (Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 925-926).
• ACOG, as summarised in Berek & Novak: Start at 21 regardless of sexual activity, and stop reasonably between 65 and 70 with adequate prior negative screens. More frequent screening applies to HIV-positive, immunosuppressed and DES-exposed women, and those with prior CIN 2 or worse (Berek & Novak's Gynecology, p. 846).
• Current practice: Some of these intervals are older, and guidelines keep changing. Many now favour primary HPV testing every 5 years. Check your local guideline.

WHO elimination strategy (2020)

• 90% of girls fully vaccinated against HPV by age 15
• 70% of women screened with a high-performance test by ages 35 and 45
• 90% of women with precancer or invasive cancer treated

More definitions: cervical cancer and its prevention

Disease terms

• Cervical cancer: A malignancy of the uterine cervix, usually squamous cell carcinoma. It is caused by persistent infection with high-risk HPV (types 16 and 18 are the most important).
• Transformation zone: The area where columnar epithelium is replaced by squamous epithelium. It is the site where most HPV-related neoplasia arises, and it is the area sampled on a Pap smear.
• Dysplasia: An older term for abnormal epithelial maturation. It signals the potential for malignant change (Berek & Novak's Gynecology, p. 833-834).
• Carcinoma in situ (CIS): Severe dysplasia confined to the epithelium, with no invasion through the basement membrane. It is now included in CIN 3 (Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 922).
• Cervical intraepithelial neoplasia (CIN): A system introduced in 1968 that grades by how much of the epithelium is occupied by immature cells and mitoses (Berek & Novak's Gynecology, p. 833-834):
  • CIN 1: Changes are limited to the lower third of the epithelium.
  • CIN 2: Changes involve up to the middle third.
  • CIN 3: Changes involve the upper third, up to full thickness.
• Squamous intraepithelial lesion (SIL): A simplified two-tier system, used because management is two-tiered (observe versus treat). CIN 1 is renamed LSIL, and CIN 2 plus CIN 3 are combined as HSIL (Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 922).
  • LSIL: This is a productive HPV infection with high viral replication but only mild changes in host cells. Most cases regress spontaneously. It is about 10 times more common than HSIL and is not treated as a premalignant lesion.
  • HSIL: HPV deregulates the cell cycle. Maturation is reduced or arrested and viral replication is lower than in LSIL. The risk of progression to carcinoma is high.
• Koilocyte: A squamous cell with a perinuclear halo and nuclear atypia. It is the cytologic hallmark of HPV infection and of LSIL.

Screening and diagnosis terms

• Pap smear (cytology): Cells from the transformation zone are fixed and stained by the Papanicolaou method, then examined for abnormal cells.
• Bethesda system: The standard cytology reporting system. Its categories include NILM (negative for intraepithelial lesion or malignancy), ASC-US, LSIL and HSIL.
• Co-testing: HPV DNA testing together with cytology, generally for women aged 30 and over.
• Primary HPV screening: HPV testing alone as the first-line screening test.
• Reflex HPV testing / ASC-US triage: An HPV test is run on the sample when cytology shows ASC-US, to decide whether to refer for colposcopy.
• Colposcopy: Magnified examination of the cervix after acetic acid application. Abnormal epithelium appears white (aceto-white) and is biopsied.
• VIA (visual inspection with acetic acid): A low-resource screen done with the naked eye after acetic acid is applied. It is often paired with "screen and treat".

Treatment terms

• Ablative treatment: Destroys abnormal tissue, e.g. cryotherapy or thermal ablation.
• LEEP / LLETZ: Loop electrosurgical excision procedure, also called large loop excision of the transformation zone. It excises the transformation zone with an electrified wire loop.
• Cold-knife conization: Surgical removal of a cone of cervical tissue. It is used for diagnosis and treatment, especially when invasion is suspected.
• Screen and treat: A same-visit approach in which a positive screen leads straight to treatment without further diagnostic work-up.

Vaccine and public health terms

• Bivalent, quadrivalent and 9-valent vaccines: They cover HPV 16/18; 6/11/16/18; and 6/11/16/18/31/33/45/52/58 respectively. Types 6 and 11 cause genital warts and do not cause cancer.
• Herd immunity: Indirect protection of unvaccinated people when enough of the population is vaccinated.
• Elimination threshold: WHO defines elimination as a public health problem as an incidence below 4 per 100,000 women per year.

Summary and conclusions: prevention of cervical cancer

Summary

• Cause: Cervical cancer follows persistent infection with high-risk HPV, mainly types 16 and 18.
• Natural history: Most cancers arise from precursor lesions over years. These run from LSIL (CIN 1) to HSIL (CIN 2 and 3) and then to invasive cancer. This long window is why prevention works.
• Primary prevention: Stops infection before it occurs.
  • HPV vaccination, ideally before sexual debut
  • Condoms and sexual health education
  • Smoking cessation
• Secondary prevention: Finds and treats precancer.
  • Screening with Pap cytology, HPV DNA testing or VIA
  • Colposcopy and biopsy for abnormal results
  • Treatment of high-grade lesions by ablation, LEEP or conization
• Tertiary prevention: Treats established cancer and limits recurrence and complications. This includes surgery, chemoradiation, follow-up and palliative care.
• Screening basics:
  • Start at about age 21.
  • Cytology is repeated every 3 years.
  • From age 30, HPV testing alone or with cytology can be repeated every 5 years if results are normal.
  • HPV testing is not advised under age 30 because transient infections make positive results unreliable.
  • High-risk groups need more frequent screening. These include HIV-positive and immunosuppressed women and those with prior CIN 2 or worse.
• Management of lesions: LSIL is usually observed because most cases regress. HSIL is treated because the progression risk is high.
• Global strategy: The WHO elimination targets for 2030 are:
  • 90% of girls vaccinated by age 15
  • 70% of women screened with a high-performance test
  • 90% of women with precancer or cancer treated
  • Elimination means an incidence below 4 per 100,000 women.

Conclusions

1. Cervical cancer is one of the most preventable cancers. It has a known viral cause, a long precancerous phase, and effective tools for both vaccination and screening.
2. The strongest approach combines vaccination (primary) with screening and treatment of precancer (secondary). Neither alone is enough.
3. Where screening is not widely practised, cervical cancer continues to cause many deaths (Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 925).
4. The burden falls mostly on low- and middle-income countries, so access and equity are central to prevention.
5. Screening intervals and tests differ between guidelines and are changing, with a trend toward primary HPV testing. Check the guideline in force locally.

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