Epithelial cell abnormalities
Squamous cell
Atypical squamous cells (ASC)
Of undetermined significance (ASC-US)
Cannot exclude HSIL (ASC-H)
Low-grade squamous intraepithelial lesion (LSIL)
Encompassing: human papillomavirus/mild dysplasia/cervical
Intraepithelial neoplasia (CIN) 1
High-grade squamous intraepithelial lesion (HSIL)
Encompassing: moderate and severe dysplasia, carcinoma in situ
CIN 2 and CIN 3
Squamous cell carcinoma
Glandular cell
Atypical glandular cells (AGC) (specify endocervical, endometrial or not otherwise specified)
Atypical glandular cells, favour neoplastic (specify endocervical or not otherwise specified)
Endocervical adenocarcinoma in situ (AIS)
Table 5.2
Risk of CIN 3 based on cytology alone
Pap −ve (%) | ASC-US (%) | LSIL (%) | ASC-H (%) | AGC (%) | HSIL (%) |
|---|---|---|---|---|---|
0.2 | 2.6 | 5.3 | 18 | 8.7 | 48 |
Table 5.3
Risk of CIN 3 based on cytology and HPV co-test
Pap −ve | ASC-US | LSIL | ASC-H | AGC | HSIL | |
|---|---|---|---|---|---|---|
HPV −ve | 0.08 | 0.45 | 2.1 | 3.8 | 1.1 | 29 |
HPV +ve | 3.5 | 6.8 | 6.2 | 25 | 34 | 50 |
5.1.1 Atypical Squamous Cells of Undetermined Significance (ASC-US) [2, 6–8]
Management of Women Aged 25 Years or Older
Guidelines for workup of ASC-US are based on the following observations:
ASC-US is the most common cytologic abnormality. It carries the lowest risk of CIN 3+, partly because one third to two thirds are not HPV associated. In fact, the risk of CIN 3+ was 2 %, low enough to justify annual rather than semi-annual cytology to identify women with CIN 3+. Triage using HPV genotyping was considered. Women with ASC-US who also had HPV-16 or HPV-18 detected had approximately twice the risk of CIN 3+ as women with ASC-US and high-risk HPV types other than 16 or 18.
Management
Option 1
For women with ASC-US cytology, HPV testing is preferred. For women with HPV-negative ASC-US whether from reflex HPV testing or co-testing, repeat co-testing at 3 years is recommended. For women with HPV-positive ASC-US, colposcopy is recommended. Triaging ASC-US cytology with HPV reduces the referrals for colposcopy by 50 %.
When colposcopy does not identify CIN in women with HPV-positive ASC-US, co-testing at 12 months is recommended. It is recommended that HPV testing in follow-up after colposcopy not be performed at intervals of less than 12 months. If the co-test is HPV negative and cytology negative, return for age-appropriate testing in 3 years is recommended. If all tests are negative at that time, routine screening is recommended.
Option 2
For women with ASC-US cytology and no HPV result, repeat cytology at 1 year is acceptable. If the result is ASC-US or worse, colposcopy is recommended; if the result is negative, return to cytology testing at 3-year intervals is recommended.
In our centre, we opt for HPV test if the patient can afford, because this is not available in our hospital setting. Repeat Pap smear at 1 year is offered if patient is reliable for follow-up. Though guidelines don’t suggest colposcopy as the first option for the work up of ASC-US cytology, we offer colposcopy as first choice to patients who cannot afford HPV testing and are noncompliant. Depending on the availability of facility at one’s centre, one can individualize the management.
5.1.1.1 ASC-US in Special Populations
Women Aged 21–24 Years
For women aged 21–24 years with ASC-US, cytology alone at 12-month intervals is preferred, but reflex HPV testing is acceptable. If reflex HPV testing is performed with ASC-US and the HPV result is positive, repeat cytology in 12 months is recommended.
Immediate colposcopy or repeat HPV testing is not recommended. If reflex HPV testing is performed and is negative, return for routine screening with cytology alone in 3 years is recommended.
Follow-Up
For women with ASC-H or HSIL+ (HSIL, atypical glandular cells [AGC] or cancer) at the 12-month follow-up, colposcopy is recommended. For women with ASC-US or worse at the 24-month follow-up, colposcopy is recommended. For women with two consecutive negative results, return to routine screening is recommended.
Women Aged 65 Years and Older
Postmenopausal women with ASC-US should be managed in the same manner as women in the general population, except when considering exit from screening for women aged 65 years and older. HPV-negative ASC-US is considered abnormal for these women as they have a higher risk for cervical cancer during follow-up than women with negative co-testing, suggesting that they need continued screening. Additional surveillance is recommended with repeat screening in 1 year; co-testing is preferred, but cytology is acceptable.
Pregnant Women
Management options for pregnant women with ASC-US are identical to those described for nonpregnant women, with the exception that deferring colposcopy until 6 weeks postpartum is acceptable. Endocervical curettage in pregnant women is unacceptable. For pregnant women who have no cytologic, histologic or colposcopically suspected CIN 2+ at the initial colposcopy, postpartum follow-up is recommended.
5.1.2 Low-Grade Squamous Intraepithelial Lesion [2, 9, 10]
Low-grade squamous intraepithelial lesions are highly associated with HPV infection, with HPV positivity of 77 %. High rate of HPV positivity in LSIL does not favour reflex HPV testing to select women for colposcopy. The ASC-US-LSIL Triage Study showed that the natural history of LSIL approximates that of HPV-positive ASC-US. Women with LSIL at ages 21–24 years carry a lower risk of CIN 3+ than older women.
Management of Women with LSIL
For women with LSIL cytology and either no HPV test or a positive HPV test, colposcopy is recommended. If co-testing shows HPV-negative LSIL, repeat co-testing at 1 year is preferred, but colposcopy is acceptable. If repeat co-testing at 1 year is elected and if the cytology is ASC-US or worse or the HPV test is positive (i.e. if the co-testing result is other than HPV negative, cytology negative), colposcopy is recommended. If the co-testing result at 1 year is HPV negative and cytology negative, repeat co-testing after 3 years is recommended. If all tests are negative at that time, routine screening is recommended.
5.1.2.1 LSIL in Special Populations
Women Aged 21–24 Years
For women with LSIL who are aged 21–24 years, follow-up with cytology at 12-month intervals is recommended. Colposcopy is not recommended. For women with ASC-H or HSIL+ at the 12-month follow-up, colposcopy is recommended. For women with ASC-US or worse at the 24-month follow-up, colposcopy is recommended. For women with two consecutive negative results, return to routine screening is recommended.
Pregnant Women
For pregnant women with LSIL, colposcopy is preferred. Endocervical curettage in pregnant women is unacceptable. For pregnant women aged 21–24 years, follow-up according to the guidelines for management of LSIL in women aged 21–24 years is recommended. Deferring colposcopy until 6 weeks postpartum is acceptable. For pregnant women who have no cytologic, histologic or colposcopically suspected CIN 2+ at the initial colposcopy, postpartum follow-up is recommended. Additional colposcopic and cytologic examinations during pregnancy are unacceptable for these women.
Postmenopausal Women
Acceptable options for the management of postmenopausal women with LSIL and no HPV test include obtaining HPV testing, repeat cytologic testing at 6 and 12 months and colposcopy. If the HPV test is negative or if CIN is not identified at colposcopy, repeat cytology in 12 months is recommended. If either the HPV test is positive or repeat cytology is ASC-US or greater, colposcopy is recommended. If two consecutive repeat cytology tests are negative, return to routine screening is recommended.
Many times cytologic abnormality of LSIL in menopausal women is due to vaginal mucosal atrophy; in that case, it is prudent to treat with local oestrogen cream for 3 weeks or oral conjugated oestrogens and then repeat the cytology.
5.1.3 Atypical Squamous Cells, Cannot Exclude High-Grade Squamous Intraepithelial Lesion (ASC-H) [2, 11]
ASC-H have a higher risk for CIN 3+ than ASC-US or LSIL although risk is lower than HSIL (Table 5.2). The risk of is also true for women aged 21–24 years, although their risk of CIN 3+ is lower than that for older women with ASC-H. There is high rate of HPV detection in women with ASC-H making reflex HPV testing unsuitable. Also, the 5-year cancer risk among women with HPV-negative ASC-H is 2 %, which is too high to justify observation.
For women with ASC-H cytology, colposcopy is recommended regardless of HPV result. Reflex HPV testing is not recommended.
5.1.3.1 ASC-H in Special Populations
Women Aged 21–24 Years
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