High-grade squamous intraepithelial lesion on cervical biopsy

The uterus is the place where women conceive and nurture life. It is the most vulnerable organ in the female body and the one that needs the most protection. Once the uterus is damaged, it affects not only one person but also the whole family. The number of women suffering from cervical cancer is increasing, often life-threatening. Cervical cancer is also known in medicine as high-grade squamous intraepithelial lesion in cervical biopsy. Next, let us understand what disease it is.

What is high-grade cervical squamous intraepithelial lesion?

High-grade cervical squamous intraepithelial lesion is a diagnostic term shared by both cytopathology and histopathology, but the two are not completely equivalent.

In 2012, the College of American Pathologists

The American Society for Colposcopy and Cervical Pathologists (CAP)

The Lower Anogenital Squamous Terminology Standardization Project was jointly published by the American College of Surgeons and Cervical Pathologists (ASCCP).

The LAST project is a revision of the nomenclature for HPV-Associated Lesions in the lower genital tract, including the cervix, and recommends the use of squamous intraepithelial lesions.

Squamous intraepithelial lesions are named after squamous intraepithelial lesions (SIL) and are divided into 2 grades: low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL). p16 immunohistochemical staining is negative for LSIL, and positive for HSIL.

In the "Fourth Edition of WHO Classification (2014)", the classification of cervical squamous cell precursor lesions has undergone corresponding changes, see Table 1.

Image source: Shen Danhua. Nomenclature of cervical squamous cell precursor lesions and corresponding clinical treatment principles - based on the "Fourth Edition of the World Health Organization Classification of Tumors of the Female Reproductive System". Chinese Journal of Obstetrics and Gynecology (Electronic Edition),

2016; 12(4): 379-382.

What is HSIL? Simply put, HSIL refers to SIL that has a significant risk of progressing to invasive cervical cancer if not treated. HSIL refers to: CINⅡ, CINⅢ, moderate atypical hyperplasia, severe atypical hyperplasia and cervical squamous cell carcinoma in situ. HSIL detected by cervical cytology such as TCT cannot be equated with a histopathological diagnosis of HSIL.

Pictures of cervical cytology examination: Picture A shows normal squamous cells, Picture B shows LSIL, Pictures C and D show HSIL, which are CIN2 and CIN3 respectively. It can be seen that as the disease progresses, the cytoplasm gradually decreases while the nuclear-to-cytoplasmic ratio increases.

Will HSIL progress to cervical cancer?

A study of nearly one million cervical cell samples from women aged 30 to 64 showed that

Negative accounted for 96%,

Atypical cell changes of no clear significance accounted for 2.8%,

LSIL accounts for 0.97%,

HSIL accounts for 0.21%,

Atypical glandular cells accounted for 0.21%,

Squamous cell carcinoma accounts for 4.5/100,000.

Five years of follow-up of women with HSIL cytology results revealed that

If HPV is positive, the chance of developing CIN2 is 71%, the chance of developing CIN3 is 49%, and the possibility of progression to cervical cancer is 6.6%;

If HPV is negative, the chance of developing CIN2 is 49%, the chance of developing CIN3 is 30%, and the possibility of progression to cervical cancer is 6.8%.

Another 2-year follow-up study of squamous intraepithelial lesions showed that

· In patients with LSIL, 60% may revert and 10% may progress to HSIL;

· For HSIL patients, 30% may revert, and about 10% progress to cervical cancer within 2-10 years.

What should I do if HSIL is found in cytology?

If HSIL is detected in cytology, there is a risk of high-grade cervical squamous intraepithelial lesions, which require early evaluation and treatment.

The "Expert Consensus on Cervical Cancer Screening and Abnormal Management in China (Part 1)" released by CSCCP in March this year pointed out that the average detection rate of HSIL in cytology in the population reported abroad is 0.45%. The probability of diagnosing ≥CIN2 in cervical biopsy under colposcopy guidance is 70%~75%, the probability of diagnosing ≥CIN2 in cervical loop electrosurgical excision procedure (LEEP) specimens is 84%~97%, and invasive cancer is 1%~2%. When cytology is HSIL, colposcopy should be referred immediately.

How to make a histopathological diagnosis of HSIL?

Histopathological diagnosis is the gold standard for the diagnosis of cervical lesions. In pathological diagnosis, CIN II and III should be distinguished as much as possible, and the p16 staining results should be indicated to guide clinical treatment.

The treatment principle recommended by the American ASCCP in 2012 is that patients diagnosed with HSIL by histology should be treated according to CINⅡ or Ⅲ. The specific interpretation is as follows:

Initial treatment (excluding pregnancy and young women)

For patients with a histological diagnosis of CIN II, CIN III, or CIN II/III and adequate colposcopy, both surface destruction and lesion excision can be used.

Diagnostic cone biopsy is recommended for patients with recurrent CIN II, CIN III, or CIN II/III.

For patients with a histological diagnosis of CIN II, CIN III, or CIN II/III and inadequate colposcopy, ECC of CIN II, CIN III, or CIN II/III, or CIN of unknown grade, diagnostic cone biopsy is recommended instead of surface destruction.

Patients with CINⅡ, CINⅢ or CINⅡ/Ⅲ are not followed up with cytology and colposcopy.

· Initial treatment is not hysterectomy.

Follow-up principles

The follow-up method after cone biopsy adopts a combined screening method to improve specificity and sensitivity. Unlike the 2006 ASCCP guidelines which require follow-up at 6 months after treatment of CINⅡ, CINⅢ or CINⅡ/Ⅲ, the new guidelines recommend combined screening and follow-up at 12 and 24 months.

If the combined test result is negative, repeat testing after 3 years is recommended.

If the examination results are abnormal, colposcopy plus ECC is recommended.

If all tests are negative, routine screening for at least 20 years is recommended, even if screening is continued past age 65 years.

· For patients who test positive for HPV, no repeat treatment or hysterectomy is indicated.

Management of CIN II, CIN III, and CIN II/III in young women

Young patients with CIN II/III who have no special histological indications and adequate colposcopy can be treated or followed up with cytology and colposcopy every 6 months for 12 months.

Patients with a histological diagnosis of CIN II may be treated, but observation is best.

o Rebiopsy is recommended for worsening colposcopic lesions or for HSIL cytology or high-grade colposcopic lesions that persist for 1 year.

o If 2 consecutive cytology results are negative, 1

Joint screening after the year.

o If the test result is negative, repeat testing in 3 years is recommended.

Treatment is recommended when histology specifically indicates CIN III, CIN II with inadequate colposcopy, or CIN II/III persisting for 24 months.

Management of CIN Ⅱ, CIN Ⅲ and CIN Ⅱ/Ⅲ in pregnant women

CINⅢ does not pose a risk to pregnancy itself, but treatment during pregnancy increases the risk of bleeding and miscarriage.

Women in late pregnancy or without invasive disease who have a histological diagnosis of CIN II, CIN III, or CIN II/III can be followed up with colposcopy and cytology at intervals of no more than 12 weeks.

Repeat biopsy is only recommended if the disease worsens or cytology suggests invasive cancer.

Delay re-evaluation with a combination of colposcopy and cytology until 6 weeks after delivery.

· Diagnostic cone biopsy is recommended only if invasive cancer is suspected.

Flowchart explaining ASCCP guidelines

Principles of management of HSIL in women aged 25 years and older

1. Colposcopy

2. Perform loop electrosurgical excision procedure (LEEP) immediately.

However, LEEP cannot be performed without colposcopy for women aged 21-24 years or pregnant women.

Female aged 21-24

Women in this age group are relatively less likely to develop cervical cancer, but are more likely to be temporarily infected with HPV, which will most likely subside after the infection. A prospective study mentioned that 70% of CIN2 patients aged 13 to 24 years (average age 20.4 years) could regress naturally.

For women aged 21 to 24, observation and evaluation are first conducted, specifically cytology and colposcopy examinations are performed every 6 months for a total of 12 months. If both results are negative, a combined HPV and cytology test can be performed after 1 year. If it is still negative, a combined test can be performed again after 3 years. If an examination in the second or fifth year shows abnormal results, a colposcopy is performed. If colposcopy or cytology examination shows a tendency to malignancy for more than 1 year, a biopsy is recommended. If CIN2, 3 persists for more than 24 months, resection is recommended.

Conclusion

HSIL refers to high-grade squamous intraepithelial lesion. The cytopathological diagnosis of HSIL is not equivalent to the histopathological diagnosis of HSIL. If HSIL is found during TCT examination, immediate referral for colposcopy is recommended. If HSIL (including CIN2 and CIN3) is confirmed by histopathology, a treatment and follow-up plan should be developed based on the specific situation.