Adenocarcinoma of the Uterine Cervix and HPV

The present study will mainly aim to review and characterize the pathologic features, treatment options, and follow-up outcomes of women with in situ/microinvasive adenocarcinoma of the uterine cervix according to HPV status (positive versus negative high-risk HPV). It will evaluate the impact of HPV status on the recurrence and survival during a follow-up of five years. The present study will be a multi-institutional study including several oncological Italian Centers. Data will be retrospectively collected from January 2012 to December 2016 with a total follow-up of 5 years.

The incidence of cervical cancer in developed countries declined considerably in the last few decades. This has been possible for efficient screening programs to which HPV vaccines have been added over the past 15 years. Despite this global reduction in cervical lesions, the incidence of adenocarcinoma of the uterine cervix (AC) increases in invasive and in situ stages. This increase mainly affects women aged 30-40, with an incidence of 11.2 per 100.000 women. On the contrary, the squamous histological lesions revealed an increase in the incidence of in situ lesions and a concomitant reduction of invasive stages. These data would seem to suggest a delay in the diagnosis of cervical glandular lesions, a shorter interval of disease progression from the adenocarcinoma in situ (AIS) to infiltrating stages, or a different process of carcinogenesis.

Most glandular cervical lesions occur at an early stage. The standard of treatment for in situ or micro-invasive lesions is extra fascial hysterectomy (AIS or stage 1A1 with no LVSI) or modified radical hysterectomy with pelvic lymph node dissection (stage 1A1 with LVSI, or 1A2). In fertility-sparing treatment, conization or radical trachelectomy with pelvic lymph node dissection is an option.

Another aspect that differentiates cervical adenocarcinoma from squamous lesions is the link with HPV infection. In 2018, the International Endocervical Criteria and Classification categorized cervical glandular lesions into HPV-associated and non-HPV-associated AC. Unlike cervical squamous lesions, which are almost all linked to high-risk HPV types, AC can be HPV negative in up to 15-20% of cases. The HPV 18 genotype is the most represented in AC with a rate of 38-50% in AIS and 50% in invasive stages. Based on some studies, it appears that non-HPV-related lesions have worse outcomes. This can significantly impact screening programs where 14 high-risk HPVs are tested.

In a recent study including 341 surgical specimens of AC, 100% of non-HPV-related lesions were classified as Silva Pattern C (the worst prognostic pattern). Instead, no impact of the HPV genotype was found on 113 women with AC during a follow-up of 5 years. HPV 45 showed a shorter 5-year survival than HPV 16 or 18.

While for advanced lesions, the stage itself represents the most important prognostic factor for prognosis, in situ or micro-invasive lesions may represent the best target for evaluating HPV status impact. This may be of interest as there is the option of conservative treatment in addition to standard treatment in early stages.

Eligibility Criteria:
Inclusion Criteria:

* Women with in-situ or microinvasive (stage 1A) adenocarcinoma of the uterine cervix undergoing conization or hysterectomy, between January 2012 and December 2016.
* Women with HPV testing within 2 months before conization.
* Women should be diagnosed and managed by the corresponding center.
* Patients with adequate clinical and pathological data.

Exclusion Criteria:

* Women with previous cervical treatments.
* Women with immunological disease (e.g. HIV).
* Unavailable HPV testing before surgery.
* Women with inadequate follow-up.