Cervical Intraepithelial Neoplasia (CIN) (Dysplasia of the Cervix)

Essentials of Diagnosis

• The presumptive diagnosis is made by an abnormal Papanicolaou smear from an asymptomatic woman with no grossly visible cervical changes

• Diagnosed by colposcopically directed biopsy

General Considerations

• The squamocolumnar junction of the cervix is an area of active squamous cell proliferation

• This junction is located on the exposed vaginal portion of the cervix in childhood

• An area of metaplasia (transformation zone) is created during puberty when the squamous margin begins to encroach on the single-layered, mucus-secreting epithelium

• Infection by the human papillomavirus (HPV) may lead to cellular abnormalities, which over time may develop into squamous cell dysplasia or cancer

• There are varying degrees of dysplasia, defined by the degree of cellular atypia; all atypia must be observed and treated if persistent or worsening

• There are no specific symptoms or signs of CIN

• The presumptive diagnosis is made by cytologic screening (Papanicolaou smear) of an asymptomatic patient with no grossly visible cervical changes

• All visible abnormal cervical lesions should be biopsied

• Colposcopy is indicated when HPV screen is positive

• Treatment varies depending on the degree and extent of CIN

• Biopsies should precede treatment, except in cases of HSIL where it may be appropriate to proceed directly to a loop electrosurgical excision procedure (LEEP)

• Cryosurgery is effective for noninvasive small lesions visible on the cervix without endocervical extension

• CO₂ laser

  • Minimizes tissue destruction

  • May be used with large visible lesions

  • Involves the vaporization of the transformation zone on the cervix and the distal 5–7 mm of endocervical canal

• Loop excision (ie, LEEP)

  • When the CIN is clearly visible in its entirety, a wire loop can be used for excisional biopsy

  • Cutting and hemostasis are achieved with a low-voltage electrosurgical machine

• Conization of the cervix

  • Surgical removal of the entire transformation zone and endocervical canal

  • Should be reserved for cases of severe dysplasia (CIN III) or carcinoma in situ, particularly those with endocervical extension

  • Can be performed with scalpel, CO₂ laser, needle electrode, or large-loop excision

Follow-Up

• Because recurrence is possible—especially in the first 2 years after treatment—and because the false-negative rate of a single cervical cytologic test is 20%, close follow-up after colposcopy and biopsy is imperative

• Following any excisional or ablative procedure, co-testing (cytology and HPV DNA) should be repeated at 12-month intervals for 2 years

• If CIN II or III is identified at the margins of an endocervical curettage procedure, however, repeat cytology with endocervical curettage is preferred at 4–6 months

• If follow-up testing is normal, routine cytologic screening can be resumed

• Colposcopy and endocervical sampling should be performed for any abnormality

Prevention

• HPV 9-valent (Gardasil-9) recombinant vaccine (9vHPV)

  • Indicated for the prevention of

    • Cervical, vaginal, and vulvar cancers (in women)

    • Anal cancers (in women and men) caused by HPV types 16, 18, 31, 33, 45, 52, and 58

    • Genital warts (in women and men) caused by HPV types 6 and 11

    • Precancerous/dysplastic lesions of cervix, vagina, vulva (in women), and anus (in women and men) caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58

  • Recommended for vaccination of females and males ages 9–45 years old

• Now that HPV 9-valent (Gardasil-9) is available, the earlier HPV 4-valent vaccine known as Gardasil (for prevention of HPV types 6, 11, 16, and 18) has been discontinued in the United States

• In addition to vaccination, preventive measures include

  • Limiting the number of sexual partners

  • Using a diaphragm or condom for coitus

  • Smoking cessation and avoiding exposure to secondhand smoke

When to Refer

• Patients with CIN II/III should be referred to an experienced colposcopist

• Patients requiring conization biopsy should be referred to a gynecologist